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  • 1. Ahl, Matilda
    et al.
    Avdic, Una
    Strandberg, Maria Compagno
    Chugh, Deepti
    Andersson, Emelie
    Hållmarker, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Department of Internal Medicine, Mora Hospital, Mora, Sweden.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Deierborg, Tomas
    Ekdahl, Christine T
    Physical Activity Reduces Epilepsy Incidence: a Retrospective Cohort Study in Swedish Cross-Country Skiers and an Experimental Study in Seizure-Prone Synapsin II Knockout Mice2019In: Sports medicine - open, ISSN 2199-1170, Vol. 5, no 1, article id 52Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Epilepsy patients commonly exercise less than the general population. Animal studies indicate beneficial effects of physical activity in established epilepsy, while its effect on the development is currently less known.

    METHODS: Here, we investigated the incidence of epilepsy during 20 years in a cohort of participants from the long-distance Swedish cross-country ski race Vasaloppet (n = 197,685) and compared it to the incidence of non-participating-matched controls included in the Swedish population register (n = 197,684). Individuals diagnosed with diseases such as stroke and epilepsy before entering the race were excluded from both groups. Experimentally, we also determined how physical activity could affect the development of epilepsy in epilepsy-prone synapsin II knockout mice (SynIIKO), with and without free access to a running wheel.

    RESULTS: We identified up to 40-50% lower incidence of epilepsy in the Vasaloppet participants of all ages before retirement. A lower incidence of epilepsy in Vasaloppet participants was seen regardless of gender, education and occupation level compared to controls. The participants included both elite and recreational skiers, and in a previous survey, they have reported a higher exercise rate than the general Swedish population. Sub-analyses revealed a significantly lower incidence of epilepsy in participants with a faster compared to slower finishing time. Dividing participants according to specified epilepsy diagnoses revealed 40-50% decrease in focal and unspecified epilepsy, respectively, but no differences in generalized epilepsy. Voluntary exercise in seizure-prone SynIIKO mice for 1 month before predicted epilepsy development decreased seizure manifestation from > 70 to 40%. Brain tissue analyses following 1 month of exercise showed increased hippocampal neurogenesis (DCX-positive cells), while microglial (Iba1) and astrocytic activation (GFAP), neuronal Map2, brain-derived neurotrophic factor and its receptor tyrosine receptor kinase B intensity were unaltered. Continued exercise for additionally 2 months after predicted seizure onset in SynIIKO mice resulted in a 5-fold reduction in seizure manifestation (from 90 to 20%), while 2 months of exercise initiated at the time of predicted seizure development gave no seizure relief, suggesting exercise-induced anti-epileptogenic rather than anti-convulsive effect.

    CONCLUSION: The clinical study and the experimental findings in mice indicate that physical activity may prevent or delay the development of epilepsy.

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  • 2. Aktaa, Suleman
    et al.
    Batra, Gorav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Blackman, Daniel J
    Ludman, Peter F
    Mamas, Mamas A
    Abdel-Wahab, Mohamed
    Angelini, Gianni D
    Czerny, Martin
    Delgado, Victoria
    De Luca, Giuseppe
    Eustachio, Agricola
    Foldager, Dan
    Hamm, Christian W
    Iung, Bernard
    Mangner, Norman
    Mehilli, Julinda
    Murphy, Gavin J
    Mylotte, Darren
    Parma, Radoslaw
    Petronio, Anna Sonia
    Popescu, Bodgan A
    Sondergaard, Lars
    Teles, Rui C
    Sabaté, Manel
    Terkelsen, Christian J
    Testa, Luca
    Wu, Jianhua
    Maggioni, Aldo P
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Casadei, Barbara
    Gale, Chris P
    Data standards for transcatheter aortic valve implantation: the European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart).2023In: European Heart Journal - Quality of Care and Clinical Outcomes, ISSN 2058-5225, E-ISSN 2058-1742, Vol. 9, no 5, p. 529-536, article id qcac063Article in journal (Refereed)
    Abstract [en]

    AIMS: Standardized data definitions are necessary for the quantification of quality of care and patient outcomes in observational studies and randomised controlled trials (RCTs). The European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart) project of the European Society of Cardiology (ESC) aims to create pan-European data standards for cardiovascular diseases and interventions, including transcatheter aortic valve implantation (TAVI).

    METHODS AND RESULTS: We followed the EuroHeart methodology for cardiovascular data standard development. A Working Group of 29 members representing 12 countries was established and included a patient representative, as well as experts in the management of valvular heart disease from the European Association of Percutaneous Cardiovascular Interventions (EAPCI), the European Association of Cardiovascular Imaging (EACVI) and the Working Group on Cardiovascular Surgery. We conducted a systematic review of the literature and used a modified Delphi method to reach consensus on a final set of variables. For each variable, the Working Group provided a definition, permissible values and categorized the variable as mandatory (Level 1) or additional (Level 2) based on its clinical importance and feasibility. In total, 93 Level 1 and 113 Level 2 variables were selected, with the level 1 variables providing the dataset for registration of patients undergoing TAVI on the EuroHeart IT platform.

    CONCLUSION: This document provides details of the EuroHeart data standards for TAVI processes of care and in-hospital outcomes. In the context of EuroHeart, this will facilitate quality improvement, observational research, registry-based RCTs and post-marketing surveillance of devices and pharmacotherapies.

  • 3. Aktaa, Suleman
    et al.
    Batra, Gorav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Baigent, Colin
    Erlinge, David
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Ludman, Peter
    Maggioni, Aldo P.
    Price, Susanna
    Weston, Clive
    Casadei, Barbara
    Gale, Chris P.
    European Society of Cardiology methodology for the development of quality indicators for the quantification of cardiovascular care and outcomes2022In: European Heart Journal - Quality of Care and Clinical Outcomes, ISSN 2058-5225, E-ISSN 2058-1742, Vol. 8, no 1, p. 4-13Article, review/survey (Refereed)
    Abstract [en]

    AIMS: It is increasingly recognised that tools are required for assessing and benchmarking quality of care in order to improve it. The European Society of Cardiology (ESC) is developing a suite of quality indicators (QIs) to evaluate cardiovascular care and support the delivery of evidence-based care. This paper describes the methodology used for their development.

    METHODS AND RESULTS: We propose a four-step process for the development of the ESC QIs. For a specific clinical area with a gap in care delivery, the QI development process includes: 1) the identification of key domains of care by constructing a conceptual framework of care; 2) the construction of candidate QIs by conducting a systematic review of the literature; 3) the selection of a final set of QIs by obtaining expert opinions using the modified Delphi method; and 4) the undertaking of a feasibility assessment by evaluating different ways of defining the QI specifications for the proposed data collection source. For each of the four steps, key methodological areas need to be addressed to inform the implementation process and avoid misinterpretation of the measurement results.

    CONCLUSION: Detailing the methodology for the ESC QIs construction enables healthcare providers to develop valid and feasible metrics to measure and improve the quality of cardiovascular care. As such, high-quality evidence may be translated into clinical practice and the 'evidence-practice' gap closed.

  • 4. Alexander, John H.
    et al.
    Lopes, Renato D.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Kilaru, Rakhi
    He, Yaohua
    Mohan, Puneet
    Bhatt, Deepak L.
    Goodman, Shaun
    Verheugt, Freek W.
    Flather, Marcus
    Huber, Kurt
    Liaw, Danny
    Husted, Steen E.
    Lopez-Sendon, Jose
    De Caterina, Raffaele
    Jansky, Petr
    Darius, Harald
    Vinereanu, Dragos
    Cornel, Jan H.
    Cools, Frank
    Atar, Dan
    Luis Leiva-Pons, Jose
    Keltai, Matyas
    Ogawa, Hisao
    Pais, Prem
    Parkhomenko, Alexander
    Ruzyllo, Witold
    Diaz, Rafael
    White, Harvey
    Ruda, Mikhail
    Geraldes, Margarida
    Lawrence, Jack
    Harrington, Robert A.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Apixaban with Antiplatelet Therapy after Acute Coronary Syndrome2011In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 365, no 8, p. 699-708Article in journal (Refereed)
    Abstract [en]

    Background: Apixaban, an oral, direct factor Xa inhibitor, may reduce the risk of recurrent ischemic events when added to antiplatelet therapy after an acute coronary syndrome.

    Methods: We conducted a randomized, double-blind, placebo-controlled clinical trial comparing apixaban, at a dose of 5 mg twice daily, with placebo, in addition to standard antiplatelet therapy, in patients with a recent acute coronary syndrome and at least two additional risk factors for recurrent ischemic events.

    Results: The trial was terminated prematurely after recruitment of 7392 patients because of an increase in major bleeding events with apixaban in the absence of a counterbalancing reduction in recurrent ischemic events. With a median follow-up of 241 days, the primary outcome of cardiovascular death, myocardial infarction, or ischemic stroke occurred in 279 of the 3705 patients (7.5%) assigned to apixaban (13.2 events per 100 patient-years) and in 293 of the 3687 patients (7.9%) assigned to placebo (14.0 events per 100 patient-years) (hazard ratio with apixaban, 0.95; 95% confidence interval [CI], 0.80 to 1.11; P = 0.51). The primary safety outcome of major bleeding according to the Thrombolysis in Myocardial Infarction (TIMI) definition occurred in 46 of the 3673 patients (1.3%) who received at least one dose of apixaban (2.4 events per 100 patient-years) and in 18 of the 3642 patients (0.5%) who received at least one dose of placebo (0.9 events per 100 patient-years) (hazard ratio with apixaban, 2.59; 95% CI, 1.50 to 4.46; P = 0.001). A greater number of intracranial and fatal bleeding events occurred with apixaban than with placebo.

    Conclusions: The addition of apixaban, at a dose of 5 mg twice daily, to antiplatelet therapy in high-risk patients after an acute coronary syndrome increased the number of major bleeding events without a significant reduction in recurrent ischemic events.

  • 5.
    Alexander, Karen P.
    et al.
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Durham, NC 27710 USA..
    Weisz, Giora
    Shaare Zedek Med Ctr, Jerusalem, Israel.;Cardiovasc Res Fdn, New York, NY USA..
    Prather, Kristi
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Durham, NC 27710 USA..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Mark, Daniel B.
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Durham, NC 27710 USA..
    Anstrom, Kevin J.
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Durham, NC 27710 USA..
    Davidson-Ray, Linda
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Durham, NC 27710 USA..
    Witkowski, Adam
    Inst Cardiol, Dept Intervent Cardiol & Angiol, Warsaw, Poland..
    Mulkay, Angel J.
    Holy Name Med Ctr, Hackensack, NJ USA..
    Osmukhina, Anna
    Gilead Sci Inc, Foster City, CA 94404 USA..
    Farzaneh-Far, Ramin
    Gilead Sci Inc, Foster City, CA 94404 USA..
    Ben-Yehuda, Ori
    Cardiovasc Res Fdn, New York, NY USA.;Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY 10027 USA..
    Stone, Gregg W.
    Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY 10027 USA..
    Ohman, E. Magnus
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Durham, NC 27710 USA..
    Effects of Ranolazine on Angina and Quality of Life After Percutaneous Coronary Intervention With Incomplete Revascularization Results From the Ranolazine for Incomplete Vessel Revascularization (RIVER-PCI) Trial2016In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 133, no 1, p. 39-47Article in journal (Refereed)
    Abstract [en]

    Background Angina often persists or returns in populations following percutaneous coronary intervention (PCI). We hypothesized that ranolazine would be effective in reducing angina and improving quality of life (QOL) in incomplete revascularization (ICR) post-PCI patients. Methods and Results In RIVER-PCI, 2604 patients with a history of chronic angina who had ICR post-PCI were randomized 1:1 to oral ranolazine versus placebo; QOL analyses included 2389 randomized subjects. Angina and QOL questionnaires were collected at baseline and months 1, 6, and 12. Ranolazine patients were more likely than placebo to discontinue study drug by month 6 (20.4% versus 14.1%, P<0.001) and 12 (27.2% versus 21.3%, P<0.001). Following qualifying index PCI, the primary QOL outcome (Seattle Angina Questionnaire [SAQ] angina frequency score) improved markedly, but similarly, in the ranolazine and placebo groups, respectively, from baseline (67.324.5 versus 69.724.0, P=0.01) to month 1 (86.6 +/- 18.1 versus 85.8 +/- 18.5, P=0.27) and month 12 (88.4 +/- 17.8 versus 88.5 +/- 17.8, P=0.94). SAQ angina frequency repeated measures did not differ in adjusted analysis between groups post baseline (mean difference 1.0; 95% CI -0.2, 2.2; P=0.11). Improvement in SAQ angina frequency was observed with ranolazine at month 6 among diabetics (mean difference 3.3; 95% CI 0.6, 6.1; P=0.02) and those with more angina (baseline SAQ angina frequency 60; mean difference 3.4; 95% CI 0.6, 6.2; P=0.02), but was not maintained at month 12. Conclusions Despite ICR following PCI, there was no incremental benefit in angina or QOL measures by adding ranolazine in this angiographically-identified population. These measures markedly improved within 1 month of PCI and persisted up to 1 year in both treatment arms. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01442038.

  • 6.
    Alfredsson, Joakim
    et al.
    Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Dept Cardiol, Linköping, Sweden..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala Univ, Dept Med Sci, Cardiol, Uppsala, Sweden.;Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden..
    Erlinge, David
    Lund Univ, Dept Clin Sci, Cardiol, Lund, Sweden..
    Herlitz, Johan
    Univ Borås, Dept Hlth Sci, Borås, Sweden..
    Frobert, Ole
    Örebro Univ, Fac Med & Hlth, Dept Cardiol, Örebro, Sweden..
    Dworeck, Christian
    Univ Gothenburg, Dept Mol & Clin Med, Gothenburg, Sweden.;Univ Gothenburg, Dept Cardiol, Sahlgrenska Univ Hosp, Gothenburg, Sweden..
    Redfors, Bjorn
    Univ Gothenburg, Dept Mol & Clin Med, Gothenburg, Sweden.;Univ Gothenburg, Dept Cardiol, Sahlgrenska Univ Hosp, Gothenburg, Sweden..
    Arefalk, Gabriel
    Östlund, Ollie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden..
    Jernberg, Tomas
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Cardiol, Stockholm, Sweden..
    Mars, Katarina
    Karolinska Inst, Sodersjukhuset, Div Cardiol, Dept Clin Sci & Educ, Sjukhusbacken 10, S-11883 Stockholm, Sweden..
    Haaga, Urban
    Karlstad Cent Hosp, Dept Cardiol, Karlstad, Sweden..
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Swahn, Eva
    Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Dept Cardiol, Linköping, Sweden..
    Lawesson, Sofia Sederholm
    Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Dept Cardiol, Linköping, Sweden..
    Hofmann, Robin
    Karolinska Inst, Sodersjukhuset, Div Cardiol, Dept Clin Sci & Educ, Sjukhusbacken 10, S-11883 Stockholm, Sweden..
    Randomized comparison of early supplemental oxygen versus ambient air in patients with confirmed myocardial infarction: Sex-related outcomes from DETO2X-AMI2021In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 237, p. 13-24Article in journal (Refereed)
    Abstract [en]

    Background The purpose of this study is to investigate the impact of oxygen therapy on cardiovascular outcomes in relation to sex in patients with confirmed myocardial infarction (MI). Methods The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction trial randomized 6,629 patients to oxygen at 6 L/min for 6-12 hours or ambient air. In the present subgroup analysis including 5,010 patients (1,388 women and 3,622 men) with confirmed MI, we report the effect of supplemental oxygen on the composite of all-cause death, rehospitalization with MI, or heart failure at long-term follow-up, stratified according to sex. Results Event rate for the composite endpoint was 18.1% in women allocated to oxygen, compared to 21.4% in women allocated to ambient air (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.65-1.05). In men, the incidence was 13.6% in patients allocated to oxygen compared to 13.3% in patients allocated to ambient air (HR 1.03, 95% CI 0.86-1.23). No significant interaction in relation to sex was found ( P = .16). Irrespective of allocated treatment, the composite endpoint occurred more often in women compared to men (19.7 vs 13.4%, HR 1.51; 95% CI, 1.30-1.75). After adjustment for age alone, there was no difference between the sexes (HR 1.06, 95% CI 0.91-1.24), which remained consistent after multivariate adjustment. Conclusion Oxygen therapy in normoxemic MI patients did not significantly affect all-cause mortality or rehospitalization for MI or heart failure in women or men. The observed worse outcome in women was explained by differences in baseline characteristics, especially age. (Am Heart J 2021;237:13 & ndash;24.)

  • 7. Amarenco, Pierre
    et al.
    Denison, Hans
    Evans, Scott R
    Himmelmann, Anders
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Knutsson, Mikael
    Ladenvall, Per
    Molina, Carlos A
    Wang, Yongjun
    Johnston, S Claiborne
    Ticagrelor Added to Aspirin in Acute Ischemic Stroke or Transient Ischemic Attack in Prevention of Disabling Stroke: A Randomized Clinical Trial2020In: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157, Vol. 78, no 2, p. 177-185Article in journal (Refereed)
    Abstract [en]

    Importance: Reduction of subsequent disabling stroke is the main goal of preventive treatment in the acute setting after transient ischemic attack (TIA) or minor ischemic stroke.

    Objective: To evaluate the superiority of ticagrelor added to aspirin in preventing disabling stroke and to understand the factors associated with recurrent disabling stroke.

    Design, Setting, and Participants: The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and Aspirin for Prevention of Stroke and Death (THALES) was a randomized clinical trial conducted between January 22, 2018, and December 13, 2019, with a 30-day follow-up, at 414 hospitals in 28 countries. The trial included 11 016 patients with a noncardioembolic, nonsevere ischemic stroke or high-risk TIA, including 10 803 with modified Rankin Scale score (mRS) recorded at 30 days.

    Interventions: Ticagrelor (180-mg loading dose on day 1 followed by 90 mg twice daily for days 2-30) or placebo within 24 hours of symptom onset. All patients received aspirin, 300 to 325 mg on day 1 followed by 75 to 100 mg daily for days 2 to 30.

    Main Outcomes and Measures: Time to the occurrence of disabling stroke (progression of index event or new stroke) or death within 30 days, as measured by mRS at day 30. Disabling stroke was defined by mRS greater than 1.

    Results: Among participants with 30-day mRS greater than 1, mean age was 68.1 years, 1098 were female (42.6%), and 2670 had an ischemic stroke (95.8%) as a qualifying event. Among 11 016 patients, a primary end point with mRS greater than 1 at 30 days occurred in 221 of 5511 patients (4.0%) randomized to ticagrelor and in 260 of 5478 patients (4.7%) randomized to placebo (hazard ratio [HR], 0.83; 95% CI, 0.69-0.99, P = .04). A primary end point with mRS 0 or 1 at 30 days occurred in 70 of 5511 patients (1.3%) and 87 of 5478 patients (1.6%) (HR, 0.79; 95% CI, 0.57-1.08; P = .14). The ordinal analysis of mRS in patients with recurrent stroke showed a shift of the disability burden following a recurrent ischemic stroke in favor of ticagrelor (odds ratio, 0.77; 95% CI, 0.65-0.91; P = .002). Factors associated with disability were baseline National Institutes of Health Stroke Scale score 4 to 5, ipsilateral stenosis of at least 30%, Asian race/ethnicity, older age, and higher systolic blood pressure, while treatment with ticagrelor was associated with less disability.

    Conclusions and Relevance: In patients with TIA and minor ischemic stroke, ticagrelor added to aspirin was superior to aspirin alone in preventing disabling stroke or death at 30 days and reduced the total burden of disability owing to ischemic stroke recurrence.

    Trial Registration: ClinicalTrials.gov Identifier: NCT03354429.

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  • 8.
    Amarenco, Pierre
    et al.
    Univ Paris, Bichat Univ Hosp, Dept Neurol, Paris, France; Univ Paris, Bichat Univ Hosp, Stroke Ctr, Paris, France.
    Denison, Hans
    AstraZeneca, Biopharmaceut R&D, Gothenburg, Sweden.
    Evans, Scott R.
    George Washington Univ, Biostat Ctr, Washington, DC USA.
    Himmelmann, Anders
    AstraZeneca, Biopharmaceut R&D, Gothenburg, Sweden.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Knutsson, Mikael
    AstraZeneca, Biopharmaceut R&D, Gothenburg, Sweden.
    Ladenvall, Per
    AstraZeneca, Biopharmaceut R&D, Gothenburg, Sweden.
    Molina, Carlos A.
    Hosp Valle De Hebron, Stroke Unit, Barcelona, Spain.
    Wang, Yongjun
    Tiantan Hosp, Dept Neurol, Beijing, Peoples R China.
    Johnston, S. Claiborne
    Univ Texas Austin, Deans Off, Dell Med Sch, Austin, TX 78712 USA.
    Ticagrelor Added to Aspirin in Acute Nonsevere Ischemic Stroke or Transient Ischemic Attack of Atherosclerotic Origin2020In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 51, no 12, p. 3504-3513Article in journal (Refereed)
    Abstract [en]

    Background and Purpose:Among patients with a transient ischemic attack or minor ischemic strokes, those with ipsilateral atherosclerotic stenosis of cervicocranial vasculature have the highest risk of recurrent vascular events.

    Methods:In the double-blind THALES (The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death) trial, we randomized patients with a noncardioembolic, nonsevere ischemic stroke, or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2–30) or placebo added to aspirin (300–325 mg on day 1 followed by 75–100 mg daily for days 2–30) within 24 hours of symptom onset. The present paper reports a prespecified analysis in patients with and without ipsilateral, potentially causal atherosclerotic stenosis ≥30% of cervicocranial vasculature. The primary end point was time to the occurrence of stroke or death within 30 days.

    Results:Of 11 016 randomized patients, 2351 (21.3%) patients had an ipsilateral atherosclerotic stenosis. After 30 days, a primary end point occurred in 92/1136 (8.1%) patients with ipsilateral stenosis randomized to ticagrelor and in 132/1215 (10.9%) randomized to placebo (hazard ratio 0.73 [95% CI, 0.56–0.96], P=0.023) resulting in a number needed to treat of 34 (95% CI, 19–171). In patients without ipsilateral stenosis, the corresponding event rate was 211/4387 (4.8%) and 230/4278 (5.4%), respectively (hazard ratio, 0.89 [95% CI, 0.74–1.08]; P=0.23, Pinteraction=0.245). Severe bleeding occurred in 4 (0.4%) and 3 (0.2%) patients with ipsilateral atherosclerotic stenosis on ticagrelor and on placebo, respectively (P=NS), and in 24 (0.5%) and 4 (0.1%), respectively, in 8665 patients without ipsilateral stenosis (hazard ratio=5.87 [95% CI, 2.04–16.9], P=0.001).

    Conclusions:In this exploratory analysis comparing ticagrelor added to aspirin to aspirin alone, we found no treatment by ipsilateral atherosclerosis stenosis subgroup interaction but did identify a higher absolute risk and a greater absolute risk reduction of stroke or death at 30 days in patients with ipsilateral atherosclerosis stenosis than in those without. In this easily identified population, ticagrelor added to aspirin provided a clinically meaningful benefit with a number needed to treat of 34 (95% CI, 19–171).

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  • 9. Andell, P.
    et al.
    Erlinge, D.
    Smith, J. G.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Koul, S.
    The effect of beta-blockers on mortality in COPD patients after myocardial infarction: A Swedish nation-wide observational study2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, p. 686-687Article in journal (Refereed)
  • 10.
    Andell, P.
    et al.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    Karlsson, S.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    Mohammad, M.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    Gotberg, M.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jensen, J.
    Capio St Goran Hosp, Stockholm, Sweden..
    Frobert, O.
    Orebro Univ Hosp, Orebro, Sweden..
    Angeras, O.
    Sahlgrens Acad, Gothenburg, Sweden..
    Nilsson, J.
    Umea Univ Hosp, Umea, Sweden..
    Omerovic, E.
    Sahlgrens Acad, Gothenburg, Sweden..
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Persson, J.
    Danderyd Hosp, Stockholm, Sweden..
    Koul, S.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    Erlinge, D.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    Intravascular ultrasound guidance is associated with lower mortality in patients undergoing stenting for unprotected left main coronary artery lesions compared to angiography-guided stent implantation2016Conference paper (Refereed)
  • 11. Andell, Pontus
    et al.
    Erlinge, David
    Smith, J. Gustav
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Koul, Sasha
    beta-Blocker Use and Mortality in COPD Patients After Myocardial Infarction: A Swedish Nationwide Observational Study2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 4, article id e001611Article in journal (Refereed)
    Abstract [en]

    Background-Patients with myocardial infarction (MI) and concomitant chronic obstructive pulmonary disease (COPD) constitute a high-risk group with increased mortality. beta-Blocker therapy has been shown to reduce mortality, prevent arrhythmias, and delay heart failure development after an MI in broad populations. However, the effect of beta-blockers in COPD patients is less well established and they may also be less treated due to fear of adverse reactions. We investigated beta-blocker prescription at discharge in patients with COPD after MI. ethods and Results-Patients hospitalized for MI between 2005 and 2010 were identified from the nationwide Swedish SWEDEHEART registry. Patients with COPD who were alive and discharged after an MI were selected as the study population. In this cohort, patients who were discharged with beta-blockers were compared to patients not discharged with beta-blockers. The primary end point was all-cause mortality. A total of 4858 patients were included, of which 4086 (84.1%) were discharged with a beta-blocker while 772 (15.9%) were not. After adjusting for potential confounders including baseline characteristics, comorbidities, and in-hospital characteristics, patients discharged with a beta-blocker had lower all-cause mortality (hazard ratio 0.87, 95% CI 0.78 to 0.98) during the total follow-up time (maximum 7.2 years). In the subgroup of patients with a history of heart failure, the corresponding hazard ratio was 0.77 (95% CI 0.63 to 0.95). Conclusions-Patients with COPD discharged with beta-blockers after an MI had a lower all-cause mortality compared to patients not prescribed beta-blockers. The results indicate that MI patients with COPD may benefit from beta-blockers.

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  • 12.
    Andell, Pontus
    et al.
    Lund Univ, Dept Cardiol, Clin Sci, S-22185 Lund, Sweden..
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Cannon, Christopher P.
    Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.;Harvard Clin Res Inst, Boston, MA USA..
    Cyr, Derek D.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA..
    Himmelmann, Anders
    AstraZeneca Res & Dev, Molndal, Sweden..
    Husted, Steen
    Hosp Unit West, Dept Med, Herning Holstebro, Denmark..
    Keltai, Matyas
    Semmelweis Univ, Hungarian Inst Cardiol, H-1085 Budapest, Hungary..
    Koul, Sasha
    Lund Univ, Dept Cardiol, Clin Sci, S-22185 Lund, Sweden..
    Santoso, Anwar
    Univ Indonesia, Natl Cardiovasc Ctr, Harapan Kita Hosp, Dept Cardiol,Vasc Med,Fac Med, Jakarta, Indonesia. INSERM, U1148, Paris, France. Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, F-75877 Paris, France. Univ Paris Diderot, Sorbonne Paris Cite, Paris, France. Royal Brompton Hosp, ICMS, NHLI Imperial Coll, London SW3 6LY, England..
    Steg, Gabriel
    Storey, Robert F.
    Univ Sheffield, Dept Cardiovasc Sci, Sheffield S10 2TN, S Yorkshire, England..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Erlinge, David
    Lund Univ, Dept Cardiol, Clin Sci, S-22185 Lund, Sweden..
    Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes and Chronic Obstructive Pulmonary Disease: An Analysis From the Platelet Inhibition and Patient Outcomes (PLATO) Trial2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 10, article id e002490Article in journal (Refereed)
    Abstract [en]

    Background-Patients with chronic obstructive pulmonary disease (COPD) experiencing acute coronary syndromes (ACS) are at high risk for clinical events. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor versus clopidogrel reduced the primary endpoint of death from vascular causes, myocardial infarction, or stroke after ACS, but increased the incidence of dyspnea, which may lead clinicians to withhold ticagrelor from COPD patients. Methods and Results-In 18 624 patients with ACS randomized to treatment with ticagrelor or clopidogrel, history of COPD was recorded in 1085 (5.8%). At 1 year, the primary endpoint occurred in 17.7% of patients with COPD versus 10.4% in those without COPD (P<0.001). The 1-year event rate for the primary endpoint in COPD patients treated with ticagrelor versus clopidogrel was 14.8% versus 20.6% (hazard ratio [HR]=0.72; 95% confidence interval [CI]: 0.54 to 0.97), for death from any cause 8.4% versus 12.4% (HR=0.70; 95% CI: 0.47 to 1.04), and for PLATO-defined major bleeding rates at 1 year 14.6% versus 16.6% (HR=0.85; 95% CI: 0.61 to 1.17). Dyspnea occurred more frequently with ticagrelor (26.1% vs. 16.3%; HR=1.71; 95% CI: 1.28 to 2.30). There was no differential increase in the relative risk of dyspnea compared to non-COPD patients (HR=1.85). No COPD status-by-treatment interactions were found, showing consistency with the main trial results. Conclusions-In this post-hoc analysis, COPD patients experienced high rates of ischemic events. Ticagrelor versus clopidogrel reduced and substantially decreased the absolute risk of ischemic events (5.8%) in COPD patients, without increasing overall major bleeding events. The benefit-risk profile supports the use of ticagrelor in patients with ACS and concomitant COPD.

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  • 13. Andell, Pontus
    et al.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Östlund, Ollie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Yndigegn, Troels
    Sparv, David
    Pernow, John
    Jernberg, Tomas
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Herlitz, Johan
    Erlinge, David
    Hofmann, Robin
    Oxygen therapy in suspected acute myocardial infarction and concurrent normoxemic chronic obstructive pulmonary disease: a prespecified subgroup analysis from the DETO2X-AMI trial2020In: European Heart Journal: Acute Cardiovascular Care, ISSN 2048-8726, E-ISSN 2048-8734, Vol. 9, no 8, p. 984-992Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial did not find any benefit of oxygen therapy compared to ambient air in normoxemic patients with suspected acute myocardial infarction. Patients with chronic obstructive pulmonary disease may both benefit and be harmed by supplemental oxygen. Thus we evaluated the effect of routine oxygen therapy compared to ambient air in normoxemic chronic obstructive pulmonary disease patients with suspected acute myocardial infarction.

    METHODS AND RESULTS: A total of 6629 patients with suspected acute myocardial infarction were randomly assigned in the DETO2X-AMI trial to oxygen or ambient air. In the oxygen group ( n=3311) and the ambient air group ( n=3318), 155 and 141 patients, respectively, had chronic obstructive pulmonary disease (prevalence of 4.5%). Patients with chronic obstructive pulmonary disease were older, had more comorbid conditions and experienced a twofold higher risk of death at one year (chronic obstructive pulmonary disease: 32/296 (10.8%) vs. non-chronic obstructive pulmonary disease: 302/6333 (4.8%)). Oxygen therapy compared to ambient air was not associated with improved outcomes at 365 days (chronic obstructive pulmonary disease: all-cause mortality hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.50-1.99, Pinteraction=0.96); cardiovascular death HR 0.80, 95% CI 0.32-2.04, Pinteraction=0.59); rehospitalisation with acute myocardial infarction or death HR 1.27, 95% CI 0.71-2.28, Pinteraction=0.46); hospitalisation for heart failure or death HR 1.08, 95% CI 0.61-1.91, Pinteraction=0.77]); there were no significant treatment-by-chronic obstructive pulmonary disease interactions.

    CONCLUSIONS: Although chronic obstructive pulmonary disease patients had twice the mortality rate compared to non-chronic obstructive pulmonary disease patients, this prespecified subgroup analysis from the DETO2X-AMI trial on oxygen therapy versus ambient air in normoxemic chronic obstructive pulmonary disease patients with suspected acute myocardial infarction revealed no evidence for benefit of routine oxygen therapy consistent with the main trial's findings.

    CLINICAL TRIALS REGISTRATION: NCT02290080.

  • 14.
    Andell, Pontus
    et al.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden..
    Karlsson, Sofia
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden..
    Mohammad, Moman A.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden..
    Gotberg, Matthias
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jensen, Jens
    Karolinska Inst, Soder Sjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.;Capio St Gorans Sjukhus, Unit Med, Stockholm, Sweden..
    Frobert, Ole
    Orebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden..
    Angeras, Oskar
    Sahlgrens Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Univ Gothenburg, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Nilsson, Johan
    Umea Univ Hosp, Heart Ctr, Dept Cardiol, Umea, Sweden..
    Omerovic, Elmir
    Sahlgrens Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Univ Gothenburg, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Persson, Jonas
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Div Cardiovasc Med, Stockholm, Sweden..
    Koul, Sasha
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden..
    Erlinge, David
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden..
    Intravascular Ultrasound Guidance Is Associated With Better Outcome in Patients Undergoing Unprotected Left Main Coronary Artery Stenting Compared With Angiography Guidance Alone2017In: Circulation. Cardiovascular Interventions, ISSN 1941-7640, E-ISSN 1941-7632, Vol. 10, no 5, article id e004813Article in journal (Refereed)
    Abstract [en]

    Background: Small observational studies have indicated better outcome with intravascular ultrasound (IVUS) guidance when performing unprotected left main coronary artery (LMCA) percutaneous coronary intervention (PCI), but the overall picture remains inconclusive and warrants further investigation. We studied the impact of IVUS guidance on outcome in patients undergoing unprotected LMCA PCI in a Swedish nationwide observational study.

    Methods and Results: Patients who underwent unprotected LMCA PCI between 2005 and 2014 because of stable coronary artery disease or acute coronary syndrome were included from the nationwide SCAAR (Swedish Coronary Angiography and Angioplasty Registry). Of 2468 patients, IVUS guidance was used in 621 (25.2%). The IVUS group was younger (median age, 70 versus 75 years) and had fewer comorbidities but more complex lesions. IVUS was associated with larger stent diameters (median, 4 mm versus 3.5 mm). After adjusting for potential confounders, IVUS was associated with significantly lower occurrence of the primary composite end point of all-cause mortality, restenosis, or definite stent thrombosis (hazard ratio, 0.65; 95% confidence interval, 0.50-0.84) and all-cause mortality alone (hazard ratio, 0.62; 95% confidence interval, 0.47-0.82). In 340 propensity score-matched pairs, IVUS was also associated with significantly lower occurrence of the primary end point (hazard ratio, 0.54; 95% confidence interval, 0.37-0.80).

    Conclusions: IVUS was associated with an independent and significant outcome benefit when performing unprotected LMCA PCI. Potential mediators of this benefit include larger and more appropriately sized stents, perhaps translating into lower risk of subsequent stent thrombosis. Although residual confounding cannot be ruled out, our findings indicate a possible hazard when performing unprotected LMCA PCI without IVUS guidance.

  • 15. Andell, Pontus
    et al.
    Koul, Sasha
    Martinsson, Andreas
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jernberg, Tomas
    Smith, J Gustav
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Erlinge, David
    Impact of chronic obstructive pulmonary disease on morbidity and mortality after myocardial infarction2014In: Open heart, E-ISSN 2053-3624, Vol. 1, no 1, p. e000002-Article in journal (Refereed)
    Abstract [en]

    AIM:

    To gain a better understanding of the impact of chronic obstructive pulmonary disease (COPD) on long-term mortality in patients with myocardial infarction (MI) and identify areas where the clinical care for these patients may be improved.

    METHODS:

    Patients hospitalised for MI between 2005 and 2010 were identified from the nationwide Swedish SWEDEHEART registry. Patients with MI and a prior COPD hospital discharge diagnosis were compared to patients with MI without a prior COPD hospital discharge diagnosis for the primary endpoint of all-cause mortality at 1 year after MI. Secondary endpoints included rates of reinfarction, new-onset stroke, new-onset bleeding and new-onset heart failure at 1 year.

    RESULTS:

    A total of 81 191 MI patients were included, of which 4867 (6%) had a COPD hospital discharge diagnosis at baseline. Patients with COPD showed a significantly higher unadjusted 1-year mortality (24.6 vs 13.8%) as well as a higher rate of reinfarction, new-onset bleeding and new-onset heart failure post-MI. After adjustment for potential confounders, including comorbidities and treatment, the patients with COPD still showed a significantly higher 1-year mortality (HR 1.14, 95% CI 1.07 to 1.21) as well as a higher rate of new-onset heart failure (HR 1.35, 95% CI 1.24 to 1.47), whereas no significant association between COPD and myocardial reinfarction or new-onset bleeding remained.

    CONCLUSIONS:

    In this nationwide contemporary study, patients with COPD frequently had an atypical presentation, less often underwent revascularisation and less often received guideline-recommended secondary preventive medications of established benefit. Prior COPD was associated with a higher 1-year mortality and a higher risk of subsequent new-onset heart failure after MI. The association seems to be mainly explained by differences in background characteristics, comorbidities and treatment, although a minor part might be explained by COPD in itself. Improved in-hospital MI treatment and post-MI secondary prevention according to the guidelines may lower the mortality in this high-risk population.

  • 16.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hållmarker, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Department of Internal Medicine, Mora Hospital, Sweden.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Long-Distance Skiing and Incidence of Hypertension: A Cohort Study of 206,889 Participants in a Long-Distance Cross-Country Skiing Event2020In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 141, no 9, p. 743-750Article in journal (Refereed)
    Abstract [en]

    Background: Hypertension is the leading risk factor for death worldwide and high levels of physical activity is associated with lower incidence of hypertension. The associations of excessive levels of exercise and incidence of hypertension is less known. We aim to compare the incidence of hypertension among 206,889 participants in a long-distance cross-country skiing event and 505,542 persons randomly sampled from the general population (matched to the skiers on age sex and place of residence). Methods: Skiers best performance (in per cent of winning time) and number of completed races during the study period were associated to incidence of hypertension after participation in Vasaloppet. Hypertension was defined as prescription of blood pressure-lowering drugs as obtained from the national drug registry. Models were adjusted for sex, age, education and income (total effect). Results: During a median time-of-risk of 8.3 years skiers had lower incidence of hypertension compared to non-skiers (HR 0.59; 95% confidence interval [CI] 0.58-0.60). Among the skiers, better performance (in % of winning time) in Vasaloppet was strongly associated with lower incidence of hypertension (Fastest fifth: HR 0.41; 95% CI 0.39-0.42. Slowest fifth: 0.78 CI 0.75-0.81). The association was near linear and did not differ between sexes. Among the skiers, a weaker association of number of completed races during the study period with incidence of hypertension (1 race: HR 0.63; 95% CI 0.62-0.65.>5 races: HR 0.51; 95% CI 0.50-0.53). A sub-analysis of 10,804 participants including adjustment for lifestyle factors showed similar results. Conclusions: Participation in a long-distance skiing event was associated with 41% lower incidence of hypertension over the next 8 years, compared to non-participation; and the better the performance, the lower the incidence of hypertension. This adds to the list of beneficial effects of intensive training, as hypertension is the leading risk factor of premature death globally.

  • 17.
    Andersen, Thomas
    et al.
    Stavanger Univ Hosp, Dept Anaesthesiol, Stavanger, Norway.
    Ueland, Thor
    Univ Oslo, Natl Hosp, Res Inst Internal Med, Oslo, Norway;Univ Oslo, KG Jebsen Inflammatory Res Ctr, Oslo, Norway;Univ Oslo, Fac Med, Oslo, Norway;Univ Tromso, Jebsen Thrombosis Res & Expertise Ctr TREC, Tromso, Norway.
    Ghukasyan Lakic, Tatevik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Åkerblom, Axel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Bertilsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Aukrust, Pal
    Univ Oslo, Natl Hosp, Res Inst Internal Med, Oslo, Norway;Univ Oslo, KG Jebsen Inflammatory Res Ctr, Oslo, Norway;Univ Oslo, Fac Med, Oslo, Norway;Univ Tromso, Jebsen Thrombosis Res & Expertise Ctr TREC, Tromso, Norway;Natl Hosp Norway, Oslo Univ Hosp, Sect Clin Immunol & Infect Dis, Oslo, Norway.
    Michelsen, Annika E.
    Univ Oslo, Natl Hosp, Res Inst Internal Med, Oslo, Norway;Univ Oslo, Fac Med, Oslo, Norway.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Becker, Richard C.
    Univ Cincinnati, Coll Med, Heart Lung & Vasc Inst, Div Cardiovasc Hlth & Dis, Cincinnati, OH USA.
    Storey, Robert F.
    Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield, S Yorkshire, England.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Kontny, Frederic
    Stavanger Univ Hosp, Dept Cardiol, Stavanger, Norway;Drammen Heart Ctr, Drammen, Norway.
    C-X-C Ligand 16 Is an Independent Predictor of Cardiovascular Death and Morbidity in Acute Coronary Syndromes2019In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 39, no 11, p. 2402-2410Article in journal (Refereed)
    Abstract [en]

    Objective:

    The chemokine CXCL16 (C-X-C motif ligand 16) is a scavenger receptor for OxLDL (oxidized low-density lipoproteins) and involved in inflammation at sites of atherosclerosis. This study aimed to investigate the association of CXCL16 with clinical outcome in patients with acute coronary syndrome.

    Approach and Results:

    Serial measurements of CXCL16 were performed in a subgroup of 5142 patients randomized in the PLATO trial (Platelet Inhibition and Patient Outcome). Associations between CXCL16 and a composite of cardiovascular death, spontaneous myocardial infarction or stroke, and the individual components were assessed by multivariable Cox regression analyses. The hazard ratio per 50% increase in admission levels of CXCL16 analyzed as continuous variable was 1.64 (95% CI, 1.44-1.88), P<0.0001. This association remained statistically significant after adjustment for randomized treatment, clinical variables, CRP (C-reactive protein), leukocytes, cystatin C, NT-proBNP (N-terminal pro-brain natriuretic peptide), troponin T, GDF-15 (growth differentiation factor 15), and other biomarkers; hazard ratio 1.23 (1.05-1.45), P=0.0126. The admission level of CXCL16 was independently associated with cardiovascular death (1.50 [1.17-1.92], P=0.0014) but not with ischemic events alone, in fully adjusted analyses. No statistically independent association was found between CXCL16 measured at 1 month, or change in CXCL16 from admission to 1 month, and clinical outcomes.

    Conclusions:

    In patients with acute coronary syndrome, admission level of CXCL16 is independently related to adverse clinical outcomes, mainly driven by an association to cardiovascular death. Thus, CXCL16 measurement may enhance risk stratification in patients with this condition.

  • 18. Angeras, O.
    et al.
    Albertsson, P.
    Karason, K.
    Ramunddal, T.
    Matejka, G.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Rosengren, A.
    Omerovic, E.
    Evidence for obesity paradox in patients with acute coronary syndromes: a report from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR)2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no Suppl 1, p. 122-122Article in journal (Other academic)
  • 19. Angeras, O.
    et al.
    Koul, S.
    Albertsson, P.
    Matejka, G.
    Schersten, F.
    Frobert, O.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Erlinge, D.
    Omerovic, E.
    Heparin versus bivalirudin in patients with non ST-elevation acute coronary syndrome undergoing percutaneous coronary intervention - a report from SCAAR2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no S1, p. 353-353Article in journal (Other academic)
  • 20. Angeras, Oskar
    et al.
    Albertsson, Per
    Karason, Kristjan
    Ramunddal, Truls
    Matejka, Goran
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Rosengren, Annika
    Omerovic, Elmir
    Evidence for obesity paradox in patients with acute coronary syndromes: a report from the Swedish Coronary Angiography and Angioplasty Registry2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no 5, p. 345-353Article in journal (Refereed)
    Abstract [en]

    The obesity paradox refers to the epidemiological evidence that obesity compared with normal weight is associated with counter-intuitive improved health in a variety of disease conditions. The aim of this study was to investigate the relationship between body mass index (BMI) and mortality in patients with acute coronary syndromes (ACSs). We extracted data from the Swedish Coronary Angiography and Angioplasty Registry and identified 64 436 patients who underwent coronary angiography due to ACSs. In 54 419 (84.4) patients, a significant coronary stenosis was identified, whereas 10 017 (15.6) patients had no significant stenosis. Patients were divided into nine different BMI categories. The patients with significant stenosis were further subdivided according to treatment received such as medical therapy, percutaneous coronary intervention (PCI), or coronary artery by-pass grafting. Mortality for the different subgroups during a maximum of 3 years was compared using Cox proportional hazards regression with the lean BMI category (21.0 to 23.5 kg/m(2)) as the reference group. Regardless of angiographic findings [significant or no significant coronary artery disease (CAD)] and treatment decision, the underweight group (BMI 18.5 kg/m(2)) had the greatest risk for mortality. Medical therapy and PCI-treated patients with modest overweight (BMI category 26.528 kg/m(2)) had the lowest risk of mortality [hazard ratio (HR) 0.52; 95 CI 0.340.80 and HR 0.64; 95 CI 0.500.81, respectively]. When studying BMI as a continuous variable in patients with significant CAD, the adjusted risk for mortality decreased with increasing BMI up to approximate to 35 kg/m(2) and then increased. In patients with significant CAD undergoing coronary artery by-pass grafting and in patients with no significant CAD, there was no difference in mortality risk in the overweight groups compared with the normal weight group. In this large and unselected group of patients with ACSs, the relation between BMI and mortality was U-shaped, with the nadir among overweight or obese patients and underweight and normal-weight patients having the highest risk. These data strengthen the concept of the obesity paradox substantially.

  • 21.
    Angeras, Oskar
    et al.
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Haraldsson, Inger
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Redfors, Bjorn
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Frobert, Ole
    Orebro Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Petursson, Petur
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Albertsson, Per
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Ioanes, Dan
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Odenstedt, Jacob
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Olsson, Hans
    Karlstad Hosp, Dept Cardiol, Karlstad, Sweden..
    Witt, Nils
    South Hosp Stockholm, Dept Cardiol, Stockholm, Sweden..
    Ruck, Andreas
    Karolinska Univ Hosp, Karolinska Inst, Dept Cardiol, Stockholm, Sweden..
    Millgard, Jonas
    Sunderby Hosp, Dept Cardiol, Sunderbyn, Sweden..
    Nilsson, Johan
    Umea Univ Hosp, Dept Cardiol, Heart Ctr, Umea, Sweden..
    Persson, Jonas
    Danderyd Hosp, Dept Cardiol, Stockholm, Sweden..
    Soderbom, Mans
    Univ Gothenburg, Dept Econ, Gothenburg, Sweden..
    Wedel, Hans
    Univ Gothenburg, Hlth Metr, Sahlgrenska Acad, Gothenburg, Sweden..
    Erlinge, David
    Lund Univ, Dept Cardiol, Lund, Sweden..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ramunddal, Truls
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Omerovic, Elmir
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Impact of Thrombus Aspiration on Mortality, Stent Thrombosis, and Stroke in Patients With ST-Segment-Elevation Myocardial Infarction: A Report From the Swedish Coronary Angiography and Angioplasty Registry2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 1, article id e007680Article in journal (Refereed)
    Abstract [en]

    Background-Thrombus aspiration is still being used in a substantial number of patients despite 2 large randomized clinical trials showing no favorable effect of routine thrombus aspiration during primary percutaneous coronary intervention in patients with STsegment- elevation myocardial infarction. The aim of this observational study was to evaluate the impact of thrombus aspiration on mortality, stent thrombosis, and stroke using all available data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Methods and Results-We identified 42 829 consecutive patients registered in SCAAR between January 2005 and September 2014 who underwent percutaneous coronary intervention for ST-segment-elevation myocardial infarction. Thrombus aspiration was used in 25% of the procedures. We used instrumental variable analysis with administrative healthcare region as the treatmentpreference instrumental variable to evaluate the effect of thrombus aspiration on mortality, stent thrombosis, and stroke. Thrombus aspiration was not associated with mortality at 30 days (risk reduction: -1.2; 95% confidence interval [CI], -5.4 to 3.0; P=0.57) and 1 year (risk reduction: -2.4; 95% CI, -7.6 to 3.0; P=0.37). Thrombus aspiration was associated with a lower risk of stent thrombosis both at 30 days (risk reduction: -2.7; 95% CI, -4.1 to -1.4; P<0.001) and 1 year (risk reduction: -3.5; 95% CI, -5.3 to -1.7; P<0.001). In-hospital stroke and neurologic complications did not differ between groups (risk reduction: 0.1; 95% CI, -0.8 to 1.1; P=0.76). Conclusions-Mortality was not different between the groups. Thrombus aspiration was associated with decreased risk of stent thrombosis. Our study provides important evidence for the external validity of previous randomized studies regarding mortality.

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  • 22.
    Angiolillo, Dominick J.
    et al.
    Univ Florida, Coll Med, Div Cardiol, Jacksonville, FL USA..
    Rollini, Fabiana
    Univ Florida, Coll Med, Div Cardiol, Jacksonville, FL USA..
    Storey, Robert F.
    Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield, S Yorkshire, England..
    Bhatt, Deepak L.
    Brigham & Womens Hosp, Harvard Med Sch, Heart & Vasc Ctr, Boston, MA USA..
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Schneider, David J.
    Univ Vermont, Cardiovasc Res Inst, Cardiol Unit, Dept Med, Burlington, VT 05405 USA..
    Sibbing, Dirk
    Ludwig Maximilians Univ Munchen, Dept Cardiol, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Berlin, Germany..
    So, Derek Y. F.
    Univ Ottawa, Heart Inst, Div Cardiol, Ottawa, ON, Canada..
    Trenk, Dietmar
    Univ Heart Ctr Freiburg Bad Krozingen, Dept Cardiol & Angiol 2, Freiberg, Germany..
    Alexopoulos, Dimitrios
    Natl & Capodistrian Univ Athens, Dept Cardiol 2, Attikon Univ Hosp, Athens, Greece..
    Gurbel, Paul A.
    Inova Heart & Vasc Inst, Inova Ctr Thrombosis Res & Drug Dev, Falls Church, VA USA..
    Hochholzer, Willibald
    Univ Heart Ctr Freiburg Bad Krozingen, Dept Cardiol & Angiol 2, Freiberg, Germany..
    De Luca, Leonardo
    San Giovanni Evangelista Hosp, Lab Intervent Cardiol, Div Cardiol, Tivoli Rome, Italy.;Mediterranean Acad Assoc Res & Studies Cardiol, Marseille, France.;Aix Marseille Univ, INSERM, UMRS 1076, Marseille, France..
    Bonello, Laurent
    Hop Nord Marseille, AP HP, Dept Cardiol, Marseille, France..
    Aradi, Daniel
    Heart Ctr Balatonfured, Budapest, Hungary.;Semmelweis Univ Budapest, Budapest, Hungary..
    Cuisset, Thomas
    CHU Timone, Dept Cardiol, Marseille, France.;Aix Marseille Univ, Fac Med, Marseille, France..
    Tantry, Udaya S.
    Inova Heart & Vasc Inst, Inova Ctr Thrombosis Res & Drug Dev, Falls Church, VA USA..
    Wang, Tracy Y.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA..
    Valgimigli, Marco
    Bern Univ Hosp, Swiss Cardiovasc Ctr Bern, Bern, Switzerland..
    Waksman, Ron
    MedStar Washington Hosp Ctr, Sect Intervent Cardiol, Washington, DC USA..
    Mehran, Roxana
    Icahn Sch Med Mt Sinai, New York, NY USA..
    Montalescot, Gilles
    Sorbonne Univ Paris 6, Hop Pitie Salpetriere, ACTION Study Grp, Paris, France..
    Franchi, Francesco
    Univ Florida, Coll Med, Div Cardiol, Jacksonville, FL USA..
    Price, Matthew J.
    Scripps Clin, Div Cardiovasc Dis, La Jolla, CA USA..
    International Expert Consensus on Switching Platelet P2Y(12) Receptor-Inhibiting Therapies2017In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 136, no 20, p. 1955-+Article in journal (Refereed)
    Abstract [en]

    Dual antiplatelet therapy with aspirin and a P2Y(12) inhibitor is the treatment of choice for the prevention of atherothrombotic events in patients with acute coronary syndromes and for those undergoing percutaneous coronary interventions. The availability of different oral P2Y(12) inhibitors (clopidogrel, prasugrel, ticagrelor) has enabled physicians to contemplate switching among therapies because of specific clinical scenarios. The recent introduction of an intravenous P2Y(12) inhibitor (cangrelor) further adds to the multitude of modalities and settings in which switching therapies may occur. In clinical practice, it is not uncommon to switch P2Y(12) inhibitor, and switching may be attributed to a variety of factors. However, concerns about the safety of switching between these agents have emerged. Practice guidelines have not fully elaborated on how to switch therapies, leaving clinicians with limited guidance on when and how to switch therapies when needed. This prompted the development of this expert consensus document by key leaders from North America and Europe with expertise in basic, translational, and clinical sciences in the field of antiplatelet therapy. This expert consensus provides an overview of the pharmacology of P2Y(12) inhibitors, different modalities and definitions of switching, and available literature and recommendations for switching between P2Y(12) inhibitors.

  • 23.
    Arefalk, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Andersen, Kasper
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Smokeless Tobacco (Snus) and Outcome of Myocardial Infarction: a SWEDEHEART StudyManuscript (preprint) (Other academic)
    Abstract [en]

    Background

    Based on effects of nicotine and snus (a smokeless tobacco) on hemodynamics, pro-arrhythmia and remodelling, in combination with indications of increased risk for fatal myocardial infarction (MI) in snus users; we hypothesised that the outcome of an MI may be worse in snus users.

    Methods

    Data was extracted from the SWEDEHEART registry for all patients who underwent coronary angiography in Sweden due to MI between December 2009 and December 2014. In snus users (n=4,950) relative to snus non-users (n=55,412), we compared risks of a large MI (defined as hs-cTnT of  > 10,000 ng/L, cTnT > 10 μg/L or cTnI > 10 μg/L) and death in the acute (in-hospital) setting, and death+HF (a combined endpoint of all-cause death or hospitalization for heart failure) and all-cause death at short- (<28 days) and long-term follow-up. Relations of snus use to outcomes were also analysed in pre-specified subgroups of never, previous and current smokers.

    Results

    A large MI was diagnosed in 10,975 patients. During long-term follow-up (median 1.9 years), 7,758 either died (n=6,044) or were hospitalized due to heart failure (n=1,714). In models adjusting for age, gender, smoking, previous MI and occupational classification (employed, unemployed/sick leave and retired), snus use was not associated with risk of large MI (odds ratio 1.01; 95% confidence interval (CI) 0.93-1.09) or death+HF (long-term Cox proportional hazard ratio (HR) 0.99; 95% CI 0.90-1.10). Nonetheless, among never-smokers snus use was associated with an increased risk for death+HF (long-term HR 1.26, 95% CI 1.03-1.55), driven by a higher mortality risk (long-term HR for death of any cause 1.29, 95% CI 1.02-1.64).

    Conclusions

    In this study, snus use was unrelated to acute, short-term or long-term adverse outcomes after an MI. Among never-smokers, snus use was associated with an increased risk of post-MI death.

  • 24. Armstrong, Paul W
    et al.
    Siha, Hany
    Fu, Yuling
    Westerhout, Cynthia M
    Steg, P Gabriel
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Storey, Robert F
    Horrow, Jay
    Katus, Hugo
    Clemmensen, Peter
    Harrington, Robert A
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    ST Elevation Acute Coronary Syndromes in PLATO: Insights from the ECG Substudy2012In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 125, no 3, p. 514-521Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Ticagrelor, when compared with clopidogrel, reduced the 12-month risk of vascular death/myocardial infarction (MI) and stroke in patients with ST-elevation acute coronary syndromes (ST-E ACS) intended to undergo primary percutaneous coronary intervention (PCI) in the PLATelet inhibition and patient Outcomes (PLATO) trial. This pre-specified electrocardiogram (ECG) substudy explored whether ticagrelor's association with vascular death and MI within one year would be amplified by: 1) the extent of baseline ST shift; and 2) subsequently associated with less residual ST changes at hospital discharge.

    METHODS AND RESULTS:

    ECGs were evaluated centrally in a core laboratory in 3,122 ticagrelor- and 3,084 clopidogrel-assigned patients having at least 1mm ST-E in two contiguous leads as identified by site investigators on the qualifying ECG. Patients with greater ST-segment shift at baseline had higher rates of vascular death/MI within one year. Amongst those who also had an ECG at hospital discharge (n=4,798), patients with ≥50% ∑ST-deviation (∑ST-dev) resolution had higher event-free survival than those with incomplete resolution (6.4% vs. 8.8%, adjusted hazard ratio 0.69 (0.54-0.88), p=0.003). The extent of ∑ST-dev resolution was similar irrespective of treatment assignment. The benefit of ticagrelor versus clopidogrel on clinical events was consistent irrespective of the extent of baseline ∑ST-dev (p(interaction)=0.728). When stratified according to conventional times from symptom onset i.e. ≤3 hours, 3-6 hours, >6 hours, the extent of baseline ∑ST-dev declined progressively over time. As time from symptom onset increased beyond three hours, the benefit of ticagrelor appeared to be more pronounced; however, the interaction between time and treatment was not significant (p=0.175).

    CONCLUSIONS:

    Ticagrelor did not modify ∑ST-dev resolution at discharge nor was its benefit affected by the extent of baseline ∑ST-dev. These hypothesis-generating observations suggest that the main effects of ticagrelor may not relate to the rapidity or the completeness of acute reperfusion, but rather the prevention of recurrent vascular events by more powerful platelet inhibition or other mechanisms.

  • 25. Armstrong, Paul W.
    et al.
    Westerhout, Cynthia M.
    Fu, Yuling
    Harrington, Robert A.
    Storey, Robert F.
    Katus, Hugo
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Quantitative ST-depression in Acute Coronary Syndromes: the PLATO Electrocardiographic Substudy2013In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 126, no 8, p. 723-+Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We evaluated whether electrocardiogram (ECG) characteristics were aligned with clinical outcomes and the effect of ticagrelor within the diverse spectrum of non-ST-elevation acute coronary syndrome patients enrolled in the PLATelet inhibition and patient Outcomes (PLATO) trial. METHODS: There were 8884 PLATO patients who had baseline ECGs assessed by a core laboratory; of these, 4935 had an ECG at hospital discharge that also was assessed. Associations with study treatment on vascular death or myocardial infarction within 1 year were examined. RESULTS: At baseline, most patients had either no or <= 0.5 mm of ST-segment depression (57%); 26% had 1.0 mm, and 17% had more extensive depression (>1.0 mm). Across the baseline ST-segment depression strata, there was a consistent treatment benefit with ticagrelor versus clopidogrel on vascular death/myocardial infarction. The extent of residual ST-segment depression at discharge was similar in the treatment groups, and the treatment effect did not differ by the extent of discharge ST-segment depression. There was a progressive increase in vascular death/myocardial infarction with increasing extent of baseline ST-segment depression (1.0 mm [vs no/0.5 mm]: hazard ratio [HR] 1.22; 95% confidence interval [CI], 1.03-1.45; > 1.0 mm: HR 1.49; 95% CI, 1.24-1.78; P < .001) and at discharge (HR 1.28; 95% CI, 1.02-1.61; HR 2.13; 95% CI, 1.54-2.95; P <. 001). CONCLUSION: The treatment effect of ticagrelor among non-ST-segment-elevation acute coronary syndrome patients was consistently expressed across all baseline ST-segment depression strata. There was no indication of an anti-ischemic benefit of ticagrelor as reflected on the discharge ECG. Our data affirm the independent prognostic relationship of both baseline and hospital discharge ST-segment depression on outcomes within 1 year in non-ST-segment-elevation acute coronary syndrome patients. 

  • 26. Attar, Rubina
    et al.
    Wu, Angie
    Wojdyla, Daniel
    Jensen, Svend Eggert
    Andell, Pontus
    Mahaffey, Kenneth W
    Roe, Matthew T
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Vemulapalli, Sreekanth
    Alexander, John H
    Lopes, Renato D
    Ohman, E Magnus
    Hernandez, Adrian F
    Patel, Manesh R
    Jones, W Schuyler
    Outcomes After Acute Coronary Syndrome in Patients With Diabetes Mellitus and Peripheral Artery Disease (from the TRACER, TRILOGY-ACS, APPRAISE-2, and PLATO Clinical Trials).2022In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 178, p. 11-17, article id S0002-9149(22)00579-3Article in journal (Refereed)
    Abstract [en]

    Patients with acute coronary syndrome (ACS) are at risk for recurrent adverse events, and multiple reports suggest that this risk is increased in patients with concomitant diabetes mellitus (DM) and peripheral artery disease (PAD). The aim of this article was to investigate cardiovascular outcomes in patients with DM presenting with ACS, stratified by PAD status. Data were derived from 4 randomized post-ACS trials (PLATO [Platelet Inhibition and Patient Outcomes], APPRAISE-2 p Apixaban for Prevention of Acute Ischemic Events 2], TRILOGY [Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage], and TRACER [Thrombin Receptor Agonist for Clinical Event Reduction in Acute Coronary Syndrome]). Using Cox regression analysis, we investigated major adverse cardiovascular events (MACEs), a composite of cardiovascular mortality, myocardial infarction (MI), or stroke and the individual components of MACE and all-cause mortality in patients with DM, presenting with ACS, stratified by PAD status as the risk modifier. This study included 15,387 patients with a diagnosis of DM and ACS, of whom 1,751 had an additional diagnosis of PAD. PAD was associated with more than doubled rates of MACE (hazard ratio [HR] 2.03, 95% confidence interval [CI] 1.81 to 2.27), all-cause mortality (HR 2.48, 95% CI 2.14 to 2.87), cardiovascular mortality (HR 2.42, 95% CI 2.04 to 2.86), and MI (HR 2.07, 95% CI 1.79 to 2.38). Patients with both PAD and DM were also more optimally treated with antihypertensive, antidiabetic, and statin medication at baseline. In conclusion, this analysis of 4 major post-ACS trials showed that patients with DM and PAD had a substantially higher risk of MACE, cardiovascular mortality, all-cause mortality, and MI despite being optimally treated with guideline-based therapies.

  • 27.
    Back, Maria
    et al.
    Sahlgrens Univ Hosp, Dept Occupat Therapy & Physiotherapy, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Linköping Univ, Dept Med & Hlth Sci, Div Physiotherapy, Linköping, Sweden.;Sahlgrens Univ Hosp, Dept Physiotherapy, Vita Straket 13, S-41345 Gothenburg, Sweden..
    Leosdottir, Margret
    Skane Univ Hosp, Dept Cardiol, Malmö, Sweden.;Lund Univ, Dept Clin Sci Malmö, Malmö, Sweden..
    Ekstrom, Mattias
    Danderyd Hosp, Dept Clin Sci, Div Cardiovasc Med, Stockholm, Sweden..
    Hambraeus, Kristina
    Falun Cent Hosp, Dept Cardiol, Falun, Sweden..
    Ravn-Fischer, Annica
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden..
    Oberg, Birgitta
    Linköping Univ, Dept Med & Hlth Sci, Div Physiotherapy, Linköping, Sweden..
    Östlund, Ollie
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    The remote exercise SWEDEHEART study-Rationale and design of a multicenter registry-based cluster randomized crossover clinical trial (RRCT)2023In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 262, p. 110-118Article in journal (Refereed)
    Abstract [en]

    Background: Despite proven benefits of exercise-based cardiac rehabilitation (EBCR), few patients with myocardial infarction (MI) participate in and complete these programs.

    Study design and objectives: The Remote Exercise SWEDEHEART study is a large multicenter registry-based cluster randomized crossover clinical trial with a planned enrollment of 1500 patients with a recent MI. Patients at intervention centers will be offered supervised EBCR, either delivered remotely, center-based or as a combination of both modes, as self -preferred choice. At control centers, patients will be offered supervised center-based EBCR, only. The duration of each time period (intervention/control) for each center will be 15 months and then cross-over occurs. The primary aim is to evaluate if remotely delivered EBCR, offered as an alternative to center-based EBCR, can increase participation in EBCR sessions. The proportion completers in each group will be presented in a supportive responder analysis. The key secondary aim is to investigate if remote EBCR is as least as effective as center-based EBCR, in terms of physical fitness and patient-reported outcome measures. Follow-up of major adverse cardiovascular events (cardiovascular-and all-cause mortality, recurrent hospitalization for acute coronary syndrome, heart failure hospitalization, stroke, and coronary revascularization) will be performed at 1 and 3 years. Safety monitoring of serious adverse events will be registered, and a cost-effectiveness analysis will be conducted to estimate the cost per quality-adjusted life-year (QALY) associated with the intervention compared with control.

    Conclusions: The cluster randomized crossover clinical trial Remote Exercise SWEDEHEART study is evaluating if par-ticipation in EBCR sessions can be increased, which may contribute to health benefits both on a group level and for individual patients including a more equal access to health care.Trial registration The study is registered at

    ClinicalTrials.gov (Identifier: NCT04260958) (Am Heart J 2023;262:110-118.)

  • 28. Bahit, M C
    et al.
    Lopes, R D
    Clare, R M
    Newby, L K
    Pieper, K S
    van der Werf, F
    Armstrong, P W
    Mahaffey, K W
    Harrington, R H
    Diaz, R
    Ohman, E M
    White, H D
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Granger, C B
    Heart failure complicating non-ST-segment elevation acute coronary syndrome: timing, predictors, and clinical outcomes2013In: JACC. Heart failure, ISSN 2213-1779, E-ISSN 2213-1787, Vol. 1, no 3, p. 223-229Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: This study sought to describe the occurrence and timing of heart failure (HF), associated clinical factors, and 30-day outcomes in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). BACKGROUND: Little is known about HF-complicating NSTE-ACS. METHODS: Using pooled patient-level data from 7 clinical trials from 1994 to 2008, we describe the occurrence and timing of HF, associated clinical factors, and 30-day outcomes in NSTE-ACS patients. HF at presentation was defined as Killip classes II to III; patients with Killip class IV or cardiogenic shock were excluded. New in-hospital cases of HF included new pulmonary edema. After adjusting for baseline variables, we created logistic regression models to identify clinical factors associated with HF at presentation and to determine the association between HF and 30-day mortality. RESULTS: Of 46,519 NSTE-ACS patients, 4,910 (10.6%) had HF at presentation. Of the 41,609 with no HF at presentation, 1,194 (2.9%) developed HF during hospitalization. A total of 40,415 (86.9%) had no HF at any time. Patients presenting with or developing HF during hospitalization were older, more often female, and had a higher risk of death at 30 days than patients without HF (adjusted odds ratio [OR]: 1.74; 95% confidence interval: 1.35 to 2.26). Older age, higher presenting heart rate, diabetes, prior myocardial infarction (MI), and enrolling MI were significantly associated with HF during hospitalization. CONCLUSIONS: In this large cohort of NSTE-ACS patients, presenting with or developing HF during hospitalization was associated with an increased risk of 30-day mortality. Research targeting new strategies to prevent and manage HF in this high-risk population is needed.

  • 29.
    Bainey, Kevin R.
    et al.
    Univ Alberta, Mazankowski Alberta Heart Inst, Edmonton, AB, Canada..
    Engstrm, Thomas
    Univ Copenhagen, Rigshosp, Heart Ctr, Copenhagen, Denmark..
    Smits, Pieter C.
    Maasstad Ziekenhuis, Dept Cardiol, Rotterdam, Netherlands..
    Gershlick, Anthony H.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Univ Hosp Leicester NHS Natl Hlth Serv Trust, Glenfield Hosp, NIHR Natl Inst Heath Res, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Storey, Robert F.
    Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield, S Yorkshire, England..
    Wood, David A.
    Univ British Columbia, Ctr Cardiovasc Innovat, Vancouver, BC, Canada..
    Mehran, Roxana
    Mt Sinai Sch Med, Zena & Michael A Weiner Cardiovasc Inst, New York, NY USA..
    Cairns, John A.
    Univ British Columbia, Div Cardiol, Vancouver, BC, Canada..
    Mehta, Shamir R.
    McMaster Univ, Populat Hlth Res Inst, Hamilton Hlth Sci, 237 Barton St E, Hamilton, ON L8L 2X2, Canada..
    Complete vs Culprit-Lesion-Only Revascularization for ST-Segment Elevation Myocardial Infarction A Systematic Review and Meta-analysis2020In: JAMA cardiology, ISSN 2380-6583, E-ISSN 2380-6591, Vol. 5, no 8, p. 881-888Article, review/survey (Refereed)
    Abstract [en]

    IMPORTANCE Recently, the Complete vs Culprit-Only Revascularization to Treat Multi vessel Disease After Early PCI (percutaneous coronary intervention) for STEMI (ST-segment elevation myocardial infarction [MI]) (COMPLETE) trial showed that angiography-guided PCI of the nonculprit lesion with the goal of complete revascularization reduced cardiovascular (CV) death or new MI compared with PCI of the culprit lesion only in STEMI. Whether complete revascularization also reduces CV mortality is uncertain. Moreover, whether the association of complete revascularization with hard clinical outcomes is consistent when fractional flow reserve (FFR)- and angiography-guided strategies are used is unknown. OBJECTIVE To determine through a systematic review and meta-analysis (1) whether complete revascularization is associated with decreased CV mortality and (2) whether heterogeneity in the association occurs when FFR- and angiography-guided PCI strategies for nonculprit lesions are performed. DATA SOURCES A systematic search of MEDLINE, Embase, ISI Web of Science, and CENTRAL (Cochrane Central Register of Controlled Trials) from database inception to September 30, 2019, was performed. Conference proceedings were also reviewed from January 1, 2002, to September 30, 2019. STUDY SELECTION English-language randomized clinical trials comparing complete revascularization vs culprit-lesion-only PCI in patients with STEMI and multivessel disease were included. DATA EXTRACTION AND SYNTHESIS The combined odds ratio (OR) was calculated with the random-effects model using the Mantel-Haenszel method (sensitivity with fixed-effects model). Heterogeneity was measured using the I-2 statistic. Publication bias was evaluated using the inverted funnel plot approach. Data were analyzed from October 2019 to January 2020. MAIN OUTCOMES AND MEASURES Cardiovascular death and the composite of CV death or new MI. RESULTS Ten randomized clinical trials involving 7030 unique patients were included. The weighted mean follow-up time was 29.5 months. Complete revascularization was associated with reduced CV death compared with culprit-lesion-only PCI (80 of 3191 [2.5%] vs 106 of 3406 [3]%1 OR, 0.69 [95% CI, 0.48-0.99]; P =.05; fixed-effects model OR, 0.74 [95% CI, 0.55-0.99]; P =.04). All-cause mortality occurred in 153 of 3426 patients (4.5%) in the complete revascularization group vs 177 of 3604 (4.9%) in the culprit-lesion-only group (OR, 0.84 [95% [I, 0.67-1.05]; P =.13; I-2 = 0%). Complete revascularization was associated with a reduced composite of CV death or new MI (192 of 2616 [7.3%] vs 266 of 2586 [10.3%]; OR, 0.69 [95% [I, 0.55-0.87]; P =.001; fixed-effects model OR, 0.69 [95% [I, 0.57-0.84]; P <.001), with no heterogeneity in this outcome when complete revascularization was performed using an FFR-guided strategy (OR, 0.78 [95% CI, 0.43-1.44]) or an angiography-guided strategy (OR, 0.61 [95% CI, 0.38-0.97]; P =.52 for interaction). CONCLUSIONS AND RELEVANCE In patients with STEMI and multivessel disease, complete revascularization was associated with a reduction in CV mortality compared with culprit-lesion-only PCI. There was no differential association with treatment between FFR- and angiography-guided strategies on major CV outcomes.

  • 30. Bakhai, A
    et al.
    Ferrieres, J
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Iniguez, A
    Mohacsi, A
    Pavlides, G
    Belger, M
    Norrbacka, K
    Sartral, M
    Treatment, outcomes, costs, and quality of life of women and men with acute coronary syndromes who have undergone percutaneous coronary intervention: results from the antiplatelet therapy observational registry2013In: Postgraduate medicine, ISSN 0032-5481, E-ISSN 1941-9260, Vol. 125, no 2, p. 100-107Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Treatment, outcomes, costs, and quality of life after percutaneous coronary intervention (PCI) were compared between women and men with acute coronary syndromes (ACS) using data from the Antiplatelet Therapy Observational Registry (APTOR). METHODS: Fourteen European countries participated in this noninterventional, prospective, observational cohort registry, which enrolled patients with ACS who underwent PCI from 2007 to 2009. The 12-month outcomes included bleeding, cardiovascular events, and mortality. Quality of life was measured using the EQ-5D (EuroQol Group) health index and the visual analog scale. RESULTS: The APTOR registry included 4546 patients, of whom 1047 (23%) were women and 3499 (77%) were men. The women were older (mean age, 67 vs 61 years) and had higher rates of diabetes mellitus and hypertension. A greater proportion of the men were smokers (40% vs 30%). Approximately 70% of the patients underwent PCI on the day of the qualifying ACS event. Women and men received similar medications at the time of PCI, hospital discharge, and 12-month follow-up visit. Bleeding, cardiovascular events, and mortality occurred at higher rates in women than in men, but the differences were not statistically significant. At 12 months post-PCI, women reported lower quality-of-life scores on the EQ-5D health index and the visual analog scale than did men. The mean total cost of care was pound6252 (euro7189) for women and pound5841 (euro6717) for men; the differences may be driven by resource use after discharge from the hospital. CONCLUSION: Women with ACS tended to be older and had more comorbidities than men, but both sexes experienced similar outcomes after 1 year. This study indicated no differences in treatment between sexes.

  • 31. Ballantyne, C.
    et al.
    Cushman, M.
    Psaty, B.
    Furberg, C.
    Khaw, K. T.
    Sandhu, M.
    Oldgren, J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Rossi, G. P.
    Maiolino, G.
    Cesari, M.
    Lenzini, L.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Rimm, E.
    Collins, R.
    Anderson, J.
    Koenig, W.
    Brenner, H.
    Rothenbacher, D.
    Berglund, G.
    Persson, M.
    Berger, P.
    Brilakis, E.
    McConnell, J. P.
    Koenig, W.
    Sacco, R.
    Elkind, M.
    Talmud, P.
    Rimm, E.
    Cannon, C. P.
    Packard, C.
    Barrett-Connor, E.
    Hofman, A.
    Kardys, I.
    Witteman, J. C.
    Criqui, M.
    Corsetti, J. P.
    Rainwater, D. L.
    Moss, A. J.
    Robins, S.
    Bloomfield, H.
    Collins, D.
    Packard, C.
    Wassertheil-Smoller, S.
    Ridker, P.
    Ballantyne, C.
    Cannon, C. P.
    Cushman, M.
    Danesh, J.
    Gu, D.
    Hofman, A.
    Nelson, J. J.
    Thompson, S.
    Zalewski, A.
    Zariffa, N.
    Di Angelantonio, E.
    Kaptoge, S.
    Thompson, A.
    Thompson, S.
    Walker, M.
    Watson, S.
    Wood, A
    Collaborative meta-analysis of individual participant data from observational studies of Lp-PLA2 and cardiovascular diseases2007In: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 14, no 1, p. 3-11Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND: A large number of observational epidemiological studies have reported generally positive associations between circulating mass and activity levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cardiovascular diseases. Few studies have been large enough to provide reliable estimates in different circumstances, such as in different subgroups (e.g., by age group, sex, or smoking status) or at different Lp-PLA2 levels. Moreover, most published studies have related disease risk only to baseline values of Lp-PLA2 markers (which can lead to substantial underestimation of any risk relationships because of within-person variability over time) and have used different approaches to adjustment for possible confounding factors. OBJECTIVES: By combination of data from individual participants from all relevant observational studies in a systematic 'meta-analysis', with correction for regression dilution (using available data on serial measurements of Lp-PLA2), the Lp-PLA2 Studies Collaboration will aim to characterize more precisely than has previously been possible the strength and shape of the age and sex-specific associations of plasma Lp-PLA2 with coronary heart disease (and, where data are sufficient, with other vascular diseases, such as ischaemic stroke). It will also help to determine to what extent such associations are independent of possible confounding factors and to explore potential sources of heterogeneity among studies, such as those related to assay methods and study design. It is anticipated that the present collaboration will serve as a framework to investigate related questions on Lp-PLA2 and cardiovascular outcomes. METHODS: A central database is being established containing data on circulating Lp-PLA2 values, sex and other potential confounding factors, age at baseline Lp-PLA2 measurement, age at event or at last follow-up, major vascular morbidity and cause-specific mortality. Information about any repeat measurements of Lp-PLA2 and potential confounding factors has been sought to allow adjustment for possible confounding and correction for regression dilution. The analyses will involve age-specific regression models. Synthesis of the available observational studies of Lp-PLA2 will yield information on a total of about 15 000 cardiovascular disease endpoints.

  • 32. Bansilal, Sameer
    et al.
    Wiviott, Stephen
    Becker, Richard
    Harrington, Robert
    Himmelmann, Anders
    Neely, Benjamin
    Husted, Steen
    Storey, Robert
    Steg, Philippe
    Katus, Hugo
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Cannon, Christopher
    The efficacy and safety of ticagrelor as compared to clopidogrel, with and without a glycoprotein iib/iia inhibitor in patients with acute coronary syndromes undergoing percutaneous intervention: a PLATO (study of platelet inhibition and patient outcomes) analysis2013In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 61, no 10, p. E1858-E1858Article in journal (Other academic)
  • 33.
    Baron, Tomasz
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Beskow, Anna H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala Biobank, Uppsala, Sweden.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Biobank linked to SWEDEHEART quality registry-routine blood sample collection opens new opportunities for cardiovascular research2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 12-15Article in journal (Refereed)
    Abstract [en]

    High-quality biobanking within routine health services, through the use of existing health-care practices and infrastructure, with respect to safety and integrity of patients in line with the Swedish Biobank Act, enables large-scale collection of biological material at reasonable costs. Complementing the extensive information on myocardial infarction patients from a national registry gives unique opportunities for research focusing on better understanding of cardiovascular disease occurrence and prognosis, developing of new diagnostic methods, and personalized treatments with greater efficacy and fewer side effects.

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  • 34.
    Baron, Tomasz
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Beskow, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Biobank kopplad till Swedeheart en resurs för framtida forskning: Erfarenheter av insamling av blodprov i hjärtsjukvården i Uppsala2013In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 110, p. CF43-Article in journal (Refereed)
  • 35.
    Baron, Tomasz
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Beskow, Anna
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    [Biobank linked to Swedeheart, a resource for future research].2013In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 110, no 38, p. 1669-1671Article in journal (Refereed)
  • 36.
    Batra, Gorav
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Andell, P.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    Erlinge, D.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Spaak, J.
    Karolinska Inst, Danderyd Univ Hosp, Dept Clin Sci, Stockholm, Sweden..
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers are associated with improved outcome but do not prevent new-onset atrial fibrillation after acute myocardial infarction2016In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 37, no Suppl. 1, p. 1387-1387, article id Abstr. P6570Article in journal (Refereed)
  • 37.
    Batra, Gorav
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Friberg, Leif
    Erlinge, David
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jernberg, Tomas
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Antithrombotic therapy after myocardial infarction in patients with atrial fibrillation undergoing percutaneous coronary intervention2018In: European Heart Journal - Cardiovascular Pharmacotherapy, ISSN 2055-6837, E-ISSN 2055-6845, Vol. 4, no 1, p. 36-45Article in journal (Refereed)
    Abstract [en]

    Aims: Optimal antithrombotic therapy after percutaneous coronary intervention (PCI) in patients with myocardial infarction (MI) and atrial fibrillation is uncertain. In this study, we compared antithrombotic regimes with regard to a composite cardiovascular outcome of all-cause mortality, MI or ischaemic stroke, and major bleeds.

    Methods and results: Patients between October 2005 and December 2012 were identified in Swedish registries, n = 7116. Landmark 0-90 and 91-365 days of outcome were evaluated with Cox-regressions, with dual antiplatelet therapy as reference. At discharge, 16.2% received triple therapy (aspirin, clopidogrel, and warfarin), 1.9% aspirin plus warfarin, 7.3% clopidogrel plus warfarin, and 60.8% dual antiplatelets. For cardiovascular outcome, adjusted hazard ratio with 95% confidence interval (HR) for triple therapy was 0.86 (0.70-1.07) for 0-90 days and 0.78 (0.58-1.05) for 91-365 days. A HR of 2.16 (1.48-3.13) and 1.61 (0.98-2.66) during 0-90 and 91-365 days, respectively, was observed for major bleeds. For aspirin plus warfarin, HR 0.82 (0.54-1.26) and 0.62 (0.48-0.79) was observed for cardiovascular outcome and 1.30 (0.60-2.85) and 1.01 (0.63-1.62) for major bleeds during 0-90 and 91-365 days, respectively. For clopidogrel plus warfarin, HR of 0.90 (0.68-1.19) and 0.68 (0.49-0.95) was observed for cardiovascular outcome and 1.28 (0.71-2.32) and 1.08 (0.57-2.04) for major bleeds during 0-90 and 91-365 days, respectively.

    Conclusion: Compared to dual antiplatelets, aspirin or clopidogrel plus warfarin therapy was associated with similar 0-90 days and lower 91-365 days of risk of the cardiovascular outcome, without higher risk of major bleeds. Triple therapy was associated with non-significant lower risk of cardiovascular outcome and higher risk of major bleeds.

  • 38.
    Batra, Gorav
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Becker, Richard C.
    Univ Cincinnati, Coll Med, Div Cardiovasc Hlth & Dis, Heart Lung & Vasc Inst, Cincinnati, OH USA..
    Harrington, Robert A.
    Stanford Univ, Dept Med, Stanford, CA USA..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Kempf, Tibor
    Hannover Med Sch, Div Mol & Translat Cardiol, Dept Cardiol & Angiol, Hannover, Germany..
    Lopes, Renato D.
    Duke Univ, Med Ctr, Dept Med, Div Cardiol,Duke Clin Res Inst, Durham, NC USA..
    Mahaffey, Kenneth W.
    Stanford Univ, Stanford Ctr Clin Res, Dept Med, Stanford, CA USA..
    Steg, Philippe Gabriel
    Univ Paris, Hop Bichat, Assistance Publ Hop Paris, Inst Natl Sante & Rech Med,Unite 1148, Paris, France..
    Storey, Robert F.
    Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield, England..
    Swahn, Eva
    Linköping Univ, Dept Cardiol, Linköping, Sweden.;Linköping Univ, Dept Med & Hlth Sci, Linköping, Sweden..
    Wollert, Kai C.
    Hannover Med Sch, Div Mol & Translat Cardiol, Dept Cardiol & Angiol, Hannover, Germany..
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Biomarker-Based Prediction of Recurrent Ischemic Events in Patients With Acute Coronary Syndromes2022In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 80, no 18, p. 1735-1747Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In patients with acute coronary syndrome (ACS), there is residual and variable risk of recurrent ischemic events.

    OBJECTIVES: This study aimed to develop biomarker-based prediction models for 1-year risk of cardiovascular (CV) death and myocardial infarction (MI) in patients with ACS undergoing percutaneous coronary intervention.

    METHODS: We included 10,713 patients from the PLATO (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome) trial in the development cohort and externally validated in 3,508 patients from the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) trial. Variables contributing to risk of CV death/MI were assessed using Cox regression models, and a score was derived using subsets of variables approximating the full model.

    RESULTS: There were 632 and 190 episodes of CV death/MI in the development and validation cohorts. The most important predictors of CV death/MI were the biomarkers, growth differentiation factor 15, and N-terminal pro-B-type natriuretic peptide, which had greater prognostic value than all candidate variables. The final model included 8 items: age (A), biomarkers (B) (growth differentiation factor 15 and N-terminal pro-B-type natriuretic peptide), and clinical variables (C) (extent of coronary artery disease, previous vascular disease, Killip class, ACS type, P2Y12 inhibitor). The model, named ABC-ACS ischemia, was well calibrated and showed good discriminatory ability for 1-year risk of CV death/MI with C-indices of 0.71 and 0.72 in the development and validation cohorts, respectively. For CV death, the score performed better, with C-indices of 0.80 and 0.84 in the development and validation cohorts, respectively.

    CONCLUSIONS: An 8-item score for the prediction of CV death/MI was developed and validated for patients with ACS undergoing percutaneous coronary intervention. The ABC-ACS ischemia score showed good calibration and discrimination and might be useful for risk prediction and decision support in patients with ACS. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872; Trial to Assess the Effects of Vorapaxar [SCH 530348; MK-5348] in Preventing Heart Attack and Stroke in Participants With Acute Coronary Syndrome [TRACER]; NCT00527943)

  • 39.
    Batra, Gorav
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Andell, Pontus
    Lund Univ, Dept Cardiol, Clin Sci, Lund, Sweden.; Skane Univ Hosp, Lund, Sweden..
    Erlinge, David
    Lund Univ, Dept Cardiol, Clin Sci, Lund, Sweden.; Skane Univ Hosp, Lund, Sweden..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Spaak, Jonas
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are associated with improved outcome but do not prevent new-onset atrial fibrillation after acute myocardial infarction2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 3, article id e005165Article in journal (Refereed)
    Abstract [en]

    Background Treatment with renin‐angiotensin system (RAS) inhibitors might restrain the structural/electrical remodeling associated with atrial fibrillation (AF). Limited evidence exists regarding the potential benefits of RAS inhibition post‐acute myocardial infarction (AMI) in patients with AF. This study sought to assess the association between RAS inhibition and all‐cause mortality and new‐onset AF in patients with/without congestive heart failure (CHF) post‐AMI.

    Methods and Results Patients hospitalized for AMI between 2006 and 2012 were identified in Swedish registries. Patients were stratified in 4 subgroups; patients with CHF and AF (n=11 489); patients with CHF without AF (n=31 676); patients with AF without CHF (n=10 066); and patients without both CHF and AF (n=59 417). Patients exposed to RAS inhibition were compared to nontreated. Three‐year risk of all‐cause mortality and new‐onset AF was assessed using adjusted Cox regression analyses. At discharge, 83 291 (73.9%) patients received RAS inhibition. RAS inhibition was associated with lower 3‐year risk of all‐cause mortality in CHF patients with AF, adjusted hazard ratio (HR) with 95% CI 0.75 (0.70–0.81), CHF patients without AF, HR 0.65 (0.60–0.69), AF patients without CHF, HR 0.82 (0.75–0.90), and in patients without CHF and AF, HR 0.76 (0.72–0.81), respectively. RAS inhibition was not associated with lower 3‐year risk of new‐onset AF in patients without AF but with/without CHF; HR 0.96 (0.84–1.10) and 1.12 (1.02–1.22), respectively.

    Conclusions RAS inhibition post‐AMI was associated with lower risk of all‐cause mortality. In patients with/without CHF, RAS inhibition was not associated with lower incidence of new‐onset AF.

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  • 40.
    Batra, Gorav
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Kunadian, Vijay
    Newcastle Univ, Fac Med Sci, Translat & Clin Res Inst, Newcastle Upon Tyne, Tyne & Wear, England.;Newcastle Upon Tyne Hosp NHS Fdn Trust, Freeman Hosp, Cardiothorac Ctr, Newcastle Upon Tyne, Tyne & Wear, England..
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Storey, Robert F.
    Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield, S Yorkshire, England..
    Steg, P. Gabriel
    Univ Paris, Hop Bichat, AP HP, French Alliance Cardiovasc Trials, Paris, France.;INSERM, U1148, Paris, France..
    Katus, Hugo A.
    Univ Klinikum Heidelberg, Med Klin, Heidelberg, Germany..
    Harrington, Robert A.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA. Beth Israel Deaconess Med Ctr, Harvard Med Sch, Dept Med, Cardiovasc Div, Boston, MA USA. Grochowski Hosp, Ctr Postgrad Med Educ, Dept Cardiol, Warsaw, Poland..
    Gibson, C. Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Budaj, Andrzej
    Center of Postgraduate Medical Education, Grochowski Hospital, Warsaw, Poland.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Effects of early myocardial reperfusion and perfusion on myocardial necrosis/dysfunction and inflammation in patients with ST-segment and non-ST-segment elevation acute coronary syndrome: results from the PLATelet inhibition and patients Outcomes (PLATO) trial2022In: European Heart Journal: Acute Cardiovascular Care, ISSN 2048-8726, E-ISSN 2048-8734, Vol. 11, no 4, p. 336-349Article in journal (Refereed)
    Abstract [en]

    Aims Restoration of myocardial blood flow and perfusion during percutaneous coronary intervention (PCI) measured using Thrombolysis in Myocardial Infarction (TIMI) flow grade (TFG) and perfusion grade (TMPG) is associated with improved outcomes in acute coronary syndrome (ACS). Associations between TFG/TMPG and changes in biomarkers reflecting myocardial damage/dysfunction and inflammation is unknown. Methods and results Among 2606 patients included, TFG was evaluated in 2198 and TMPG in 1874 with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment ACS (NSTE-ACS). Biomarkers reflecting myocardial necrosis [troponin T (TnT)], myocardial dysfunction [N-terminal prohormone brain natriuretic peptide (NT-proBNP)], inflammation [interleukin-6 (IL-6) and C-reactive protein (CRP)], and oxidative stress/ageing/inflammation [growth differentiation factor-15 (GDF-15)] were measured at baseline, discharge, and 1- and 6-month post-randomization. Associations between TFG/TMPG and changes in biomarker levels were evaluated using the Mann-Whitney-Wilcoxon signed test. In total, 1423 (54.6%) patients had STEMI and 1183 (45.4%) NSTE-ACS. Complete reperfusion after PCI with TFG = 3 was achieved in 1110 (85.3%) with STEMI and in 793 (88.5%) with NSTE-ACS. Normal myocardial perfusion with TMPG = 3 was achieved in 475 (41.6%) with STEMI and in 396 (54.0%) with NSTE-ACS. Levels of TnT, NT-proBNP, IL-6, CRP, and GDF-15 were substantially lower at discharge in patients with complete vs. incomplete TFG and STEMI (P < 0.01). This pattern was not observed for patients with NSTE-ACS. Patients with normal vs. abnormal TMPG and NSTE-ACS had lower levels of NT-proBNP at discharge (P = 0.01). Conclusions Successful restoration of epicardial blood flow in STEMI was associated with less myocardial necrosis/dysfunction and inflammation. Attainment of normal myocardial perfusion was associated with less myocardial dysfunction in NSTE-ACS.

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  • 41. Becker, Richard C
    et al.
    Bassand, Jean Pierre
    Budaj, Andrzej
    Wojdyla, Daniel M
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Cornel, Jan H
    French, John
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Horrow, Jay
    Husted, Steen
    Lopez-Sendon, Jose
    Lassila, Riitta
    Mahaffey, Kenneth W
    Storey, Robert F
    Harrington, Robert A
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bleeding complications with the P2Y12 receptor antagonists clopidogrel and ticagrelor in the PLATelet inhibition and patient Outcomes (PLATO) trial2011In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 32, no 23, p. 2933-2944Article in journal (Refereed)
    Abstract [en]

    Aims

    More intense platelet-directed therapy for acute coronary syndrome (ACS) may increase bleeding risk. The aim of the current analysis was to determine the rate, clinical impact, and predictors of major and fatal bleeding complications in the PLATO study.

    Methods and results

    PLATO was a randomized, double-blind, active control international, phase 3 clinical trial in patients with acute ST elevation and non-ST-segment elevation ACS. A total of 18 624 patients were randomized to either ticagrelor, a non-thienopyridine, reversibly binding platelet P2Y(12) receptor antagonist, or clopidogrel in addition to aspirin. Patients randomized to ticagrelor and clopidogrel had similar rates of PLATO major bleeding (11.6 vs. 11.2%; P = 0.43), TIMI major bleeding (7.9 vs. 7.7%, P = 0.56) and GUSTO severe bleeding (2.9 vs. 3.1%, P = 0.22). Procedure-related bleeding rates were also similar. Non-CABG major bleeding (4.5 vs. 3.8%, P = 0.02) and non-procedure-related major bleeding (3.1 vs. 2.3%, P = 0.05) were more common in ticagrelor-treated patients, primarily after 30 days on treatment. Fatal bleeding and transfusion rates did not differ between groups. There were no significant interactions for major bleeding or combined minor plus major bleeding between treatment groups and age ≥75 years, weight <60 kg, region, chronic kidney disease, creatinine clearance <60 mL/min, aspirin dose >325 mg on the day of randomization, pre-randomization clopidogrel administration, or clopidogrel loading dose.

    Conclusion

    Ticagrelor compared with clopidogrel was associated with similar total major bleeding but increased non-CABG and non-procedure-related major bleeding, primarily after 30 days on study drug treatment. Fatal bleeding was low and did not differ between groups.

  • 42.
    Behan, Miles W.
    et al.
    Edinburgh Heart Ctr, Edinburgh, Midlothian, Scotland..
    Haude, Michael
    Lukaskrankenhaus GmbH, Stadt Kliniken Neuss, Med Clin 1, Neuss, Germany..
    Oldroyd, Keith G.
    Golden Jubilee Natl Hosp, West Scotland Heart & Lung Ctr, Clydebank, Scotland..
    Lansky, Alexandra J.
    Yale Univ, Sch Med, Div Cardiovasc Med, New Haven, CT USA..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Baumbach, Andreas
    Bristol Heart Inst, Bristol BS2 8HW, Avon, England..
    Will this trial change my practice?: TOTAL a randomised trial of thrombus aspiration in ST-elevation myocardial infarction2015In: EuroIntervention, ISSN 1774-024X, E-ISSN 1969-6213, Vol. 11, no 3, p. 361-363Article in journal (Other academic)
  • 43. Bellavia, Andrea
    et al.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Orsini, Nicola
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Cannon, Christopher P
    Himmelmann, Anders
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Time-based measures of treatment effect: reassessment of ticagrelor and clopidogrel from the PLATO trial2017In: Open heart, E-ISSN 2053-3624, Vol. 4, no 2, article id e000557Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Treatment effects to binary endpoints using time-to-event data in randomised controlled trials are typically summarised by reporting HRs derived with Cox proportional hazard models. Alternative and complementary methods include summarising the between-treatment differences on the metric time scale, quantifying the effect as delay of the event (DoE). The aim of this study was to reassess data from the PLATO study expressing the effects as the time by which the main outcomes are delayed or hastened due to treatment.

    METHODS: PLATO was a randomised controlled double-blind multicentre study (n=18,624), conducted between 2006 and 2008, which demonstrated superiority of the antiplatelet treatment ticagrelor over clopidogrel in reducing risk of several cardiovascular events. In the present study, four of the main PLATO outcomes were reassessed by calculating the time by which an event may be delayed due to the treatment.

    RESULTS: The effects of ticagrelor, as compared with clopidogrel, consisted of a substantial delay of the evaluated outcomes, ranging from 83 to 98 days over 400-day follow-up. The Delay of Events Curves showed that the effects progressively increased over time, and the significant findings were concordant with those presented in the original PLATO study.

    CONCLUSIONS: This study confirmed evidence of a beneficial effect of ticagrelor over clopidogrel, and provided the magnitude of such effects in terms of delayed event time. Investigating time-to-event data with a percentile approach allows presenting treatment effects from randomised controlled studies as absolute measures of the time by which an event may be delayed due to the treatment.

    TRIAL REGISTRATION NUMBER: PLATO (www.clinicaltrials.gov; NCT00391872); Results.

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  • 44.
    Bergman, Sofia
    et al.
    Lund Univ, Dept Cardiol, Clin Sci, Skane Univ Hosp, S-22185 Lund, Sweden..
    Mohammad, Moman A.
    Lund Univ, Dept Cardiol, Clin Sci, Skane Univ Hosp, S-22185 Lund, Sweden..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Angerås, Oskar
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Wagner, Henrik
    Helsingborg Lasarett, Dept Cardiol, Helsingborg, Sweden..
    Jensen, Jens
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.;Capio St Gorans Hosp AB, Dept Cardiol, Stockholm, Sweden..
    Scherstén, Fredrik
    Lund Univ, Dept Cardiol, Clin Sci, Skane Univ Hosp, S-22185 Lund, Sweden..
    Fröbert, Ole
    Örebro Univ, Dept Cardiol, Fac Hlth, Örebro, Sweden..
    Koul, Sasha
    Lund Univ, Dept Cardiol, Clin Sci, Skane Univ Hosp, S-22185 Lund, Sweden..
    Erlinge, David
    Lund Univ, Dept Cardiol, Clin Sci, Skane Univ Hosp, S-22185 Lund, Sweden..
    Clinical Impact of Intraprocedural Stent Thrombosis During Percutaneous Coronary Intervention in Patients Treated With Potent P2Y12 inhibitors - a VALIDATE-SWEDEHEART Substudy2021In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 10, no 18, article id e022984Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The clinical importance of intraprocedural stent thrombosis (IPST) during percutaneous coronary intervention in the contemporary era of potent oral P2Y12 inhibitors is not established. The aim of this study was to assess IPST and its association with clinical outcome in patients with myocardial infarction undergoing percutaneous coronary intervention with contemporary antithromboticmedications.

    METHODS AND RESULTS: The VALIDATE-SWEDEHEART study (Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial) included 6006 patients with myocardial infarction, treated with potent P2Y12 inhibitors during percutaneous coronary intervention. IPST, defined as a new or worsening thrombus related to a stent deployed during the procedure, was reported by the interventional cardiologist in 55 patients (0.9%) and was significantly associated with ST-segment elevation myocardial infarction presentation, longer stents, bailout glycoprotein IIb/IIIa inhibitors, and final Thrombolysis in Myocardial Infarction flow <3. The primary composite end point included cardiovascular death, myocardial infarction, out-of-laboratory definite stent thrombosis and target vessel revascularization within 30 days. Secondary end points were major bleeding and the individual components of the primary composite end point. Patients with versus without IPST had significantly higher rates of the primary composite end point (20.0% versus 4.4%), including higher rates of cardiovascular death, target vessel revascularization, and definite stent thrombosis, but not myocardial infarction or major bleeding. By multivariable analysis, IPST was independently associated with the primary composite end point (hazard ratio, 3.82; 95% CI, 2.05-7.12; P<0.001).

    CONCLUSIONS: IPST is a rare but dangerous complication during percutaneous coronary intervention, independently associated with poor prognosis, even in the current era of potent antiplatelet agents. Future treatment studies are needed to reduce the rate of IPST and to improve the poor outcome among these patients.

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  • 45. Bergmeijer, T. O.
    et al.
    Angiolillo, D. J.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wagner, H.
    Brown, P. B.
    Zhou, C.
    Jakubowski, J. A.
    Moser, B. A.
    Erlinge, D.
    Ten Berg, J. M.
    Pharmacokinetics and pharmacodynamics of prasugrel 5 mg in low body weight patients and prasugrel 10 mg in higher body weight patients2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no Suppl 1, p. 315-315Article in journal (Other academic)
  • 46.
    Bergstrom, Goran
    et al.
    Univ Gothenburg, Inst Med, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Clin Physiol, Gothenburg, Sweden..
    Rosengren, Annika
    Univ Gothenburg, Inst Med, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrenska Univ Hosp Ostra Hosp, Dept Med Geriatr & Emergency Med, Gothenburg, Sweden..
    Brolin, Elin Bacsovics
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Capio St Goran Hosp, Dept Radiol, Stockholm, Sweden..
    Brandberg, John
    Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Dept Radiol, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Radiol, Gothenburg, Sweden..
    Cederlund, Kerstin
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Engstrom, Gunnar
    Lund Univ, Dept Clin Sci Malmö, Malmö, Sweden..
    Engvall, Jan E.
    Linköping Univ, Ctr Med Image Sci & Visualizat, CMIV, Linköping, Sweden.;Linköping Univ, Dept Clin Physiol, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden..
    Eriksson, Maria J.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Physiol, Stockholm, Sweden..
    Goncalves, Isabel
    Skane Univ Hosp, Dept Cardiol, Malmö, Sweden.;Lund Univ, Dept Clin Sci Malmö, Cardiovasc Res Translat Studies, Malmö, Sweden..
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Jernberg, Tomas
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Lilja, Mikael
    Umeå Univ, Östersund Hosp, Dept Publ Hlth & Clin Med, Unit Res Educ & Dev, Umeå, Sweden..
    Magnusson, Martin
    Lund Univ, Dept Clin Sci Malmö, Malmö, Sweden.;Skane Univ Hosp, Dept Cardiol, Malmö, Sweden.;Lund Univ, Wallenberg Ctr Mol Med, Lund, Sweden.;North West Univ, Hypertens Africa Res Team HART, Potchefstroom, South Africa..
    Persson, Anders
    Linköping Univ, Ctr Med Image Sci & Visualizat, CMIV, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Dept Radiol, Linköping, Sweden.;Karolinska Inst, Huddinge Univ Hosp, Dept Clin Sci, Stockholm, Sweden..
    Persson, Margaretha
    Lund Univ, Dept Clin Sci Malmö, Malmö, Sweden.;Skane Univ Hosp, Dept Internal Med, Malmö, Sweden..
    Sandstrom, Anette
    Umeå Univ, Heart Ctr, Umeå, Sweden.;Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Schmidt, Caroline
    Univ Gothenburg, Inst Med, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden..
    Larsson, Linn Skoglund
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Univ New South Wales, George Inst Global Hlth, Sydney, Australia..
    Swahn, Eva
    Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Dept Cardiol, Linköping, Sweden..
    Soderberg, Stefan
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Toren, Kjell
    Univ Gothenburg, Sahlgrenska Acad, Sch Publ Hlth & Community Med, Inst Med,Sect Occupat & Environm Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Occupat & Environm Med, Gothenburg, Sweden..
    Ostgren, Carl Johan
    Linköping Univ, Ctr Med Image Sci & Visualizat, CMIV, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden..
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Body weight at age 20 and in midlife is more important than weight gain for coronary atherosclerosis: Results from SCAPIS2023In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 373, p. 46-54Article in journal (Refereed)
    Abstract [en]

    Background and aims: Elevated body weight in adolescence is associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, weight in midlife or to weight gain is not known. The aim of this study is to assess the risk of midlife coronary atherosclerosis being associated with body weight at age 20, body weight in midlife and body weight change.

    Methods: We used data from 25,181 participants with no previous myocardial infarction or cardiac procedure in the Swedish CArdioPulmonary bioImage Study (SCAPIS, mean age 57 years, 51% women). Data on coronary atherosclerosis, self-reported body weight at age 20 and measured midlife weight were recorded together with potential confounders and mediators. Coronary atherosclerosis was assessed using coronary computed tomog-raphy angiography (CCTA) and expressed as segment involvement score (SIS).

    Results: The probability of having coronary atherosclerosis was markedly higher with increasing weight at age 20 and with mid-life weight (p < 0.001 for both sexes). However, weight increase from age 20 until mid-life was only modestly associated with coronary atherosclerosis. The association between weight gain and coronary atherosclerosis was mainly seen in men. However, no significant sex difference could be detected when adjusting for the 10-year delay in disease development in women.

    Conclusions: Similar in men and women, weight at age 20 and weight in midlife are strongly related to coronary atherosclerosis while weight increase from age 20 until midlife is only modestly related to coronary atherosclerosis.

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  • 47.
    Beusch, Christian M.
    et al.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Chem 1, S-17177 Stockholm, Sweden..
    Simonson, Oscar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala Univ Hosp, Dept Cardiothorac Surg & Anesthes, S-75185 Uppsala, Sweden..
    Wedin, Johan O
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery. Uppsala Univ Hosp, Dept Cardiothorac Surg & Anesthes, S-75185 Uppsala, Sweden..
    Sabatier, Pierre
    Karolinska Inst, Dept Med Biochem & Biophys, Div Chem 1, S-17177 Stockholm, Sweden.;Uppsala Univ, Dept Surg Sci, Cardiothorac Translat Med CTTM Lab, S-75237 Uppsala, Sweden.;Univ Copenhagen, Novo Nord Fdn Ctr Prot Res, DK-2200 Copenhagen, Denmark..
    Felldin, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery. Uppsala Univ Hosp, Dept Cardiothorac Surg & Anesthes, S-75185 Uppsala, Sweden..
    Kadekar, Sandeep
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Osterholm, Cecilia
    Karolinska Inst, Dept Mol Med & Surg, S-17177 Stockholm, Sweden..
    Vegvari, Akos
    Karolinska Inst, Dept Med Biochem & Biophys, Div Chem 1, S-17177 Stockholm, Sweden..
    Zubarev, Roman A.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Chem 1, S-17177 Stockholm, Sweden..
    Fromell, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala Univ Hosp, Dept Cardiothorac Surg & Anesthes, S-75185 Uppsala, Sweden..
    Grinnemo, Karl-Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery. Uppsala Univ Hosp, Dept Cardiothorac Surg & Anesthes, S-75185 Uppsala, Sweden..
    Rodin, Sergey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery. Uppsala Univ Hosp, Dept Cardiothorac Surg & Anesthes, S-75185 Uppsala, Sweden..
    Analysis of local extracellular matrix identifies different aetiologies behind bicuspid and tricuspid aortic valve degeneration and suggests therapies2023In: Cellular and Molecular Life Sciences (CMLS), ISSN 1420-682X, E-ISSN 1420-9071, Vol. 80, no 9, article id 268Article in journal (Refereed)
    Abstract [en]

    Aortic valve degeneration (AVD) is a life-threatening condition that has no medical treatment and lacks individual therapies. Although extensively studied with standard approaches, aetiologies behind AVD are unclear. We compared abundances of extracellular matrix (ECM) proteins from excised valve tissues of 88 patients with isolated AVD of normal tricuspid (TAV) and congenital bicuspid aortic valves (BAV), quantified more than 1400 proteins per ECM sample by mass spectrometry, and demonstrated that local ECM preserves molecular cues of the pathophysiological processes. The BAV ECM showed enrichment with fibrosis markers, namely Tenascin C, Osteoprotegerin, and Thrombospondin-2. The abnormal physical stress on BAV may cause a mechanical injury leading to a continuous Tenascin C-driven presence of myofibroblasts and persistent fibrosis. The TAV ECM exhibited enrichment with Annexin A3 (p = 1.1 x 10(-16) and the fold change 6.5) and a significant deficit in proteins involved in high-density lipid metabolism. These results were validated by orthogonal methods. The difference in the ECM landscape suggests distinct aetiologies between AVD of BAV and TAV; warrants different treatments of the patients with BAV and TAV; elucidates the molecular basis of AVD; and implies possible new therapeutic approaches. Our publicly available database (human_avd_ecm.surgsci. uu.se) is a rich source for medical doctors and researchers who are interested in AVD or heart ECM in general. Systematic proteomic analysis of local ECM using the methods described here may facilitate future studies of various tissues and organs in development and disease.

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  • 48.
    Bhatt, Deepak L.
    et al.
    Brigham & Womens Hosp, Heart & Vasc Ctr, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Steg, Philippe Gabriel
    Univ Paris, Hop Bichat, AP HP,INSERM,U1148, French Alliance Cardiovasc Trials,Dept Hosp Univ, Paris, France;Royal Brompton Hosp, Natl Heart & Lung Inst, London, England.
    Mehta, Shamir R.
    Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada;McMaster Univ, Hamilton, ON, Canada.
    Leiter, Lawrence A.
    Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada.
    Simon, Tabassome
    Sorbonne Univ, Hop St Antoine, AP HP, Dept Clin Pharmacol,Clin Res Platform URCEST CRB, Paris, France.
    Fox, Kim
    Royal Brompton Hosp, Natl Heart & Lung Inst, London, England.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Andersson, Marielle
    AstraZeneca BioPharmaceut Res & Dev, Late Stage Dev, Cardiovasc Renal & Metab, Molndal, Sweden.
    Himmelmann, Anders
    AstraZeneca BioPharmaceut Res & Dev, Late Stage Dev, Cardiovasc Renal & Metab, Molndal, Sweden.
    Ridderstrale, Wilhelm
    AstraZeneca BioPharmaceut Res & Dev, Late Stage Dev, Cardiovasc Renal & Metab, Molndal, Sweden.
    Chen, Jersey
    AstraZeneca BioPharmaceut Res & Dev, Late Stage Dev, Cardiovasc Renal & Metab, Gaithersburg, MD USA.
    Song, Yang
    Baim Inst Clin Res, Boston, MA USA.
    Diaz, Rafael
    Estudios Clin Latino Amer, Dept Med, Rosario, Santa Fe, Argentina.
    Goto, Shinya
    Tokai Univ, Sch Med, Dept Med Cardiol, Isehara, Kanagawa, Japan.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ray, Kausik K.
    Imperial Coll London, Dept Primary Care & Publ Hlth, Imperial Ctr Cardiovasc Dis Prevent, London, England.
    Parkhomenko, Alexander N.
    Inst Cardiol, Emergency Cardiol Dept, Kiev, Ukraine.
    Kosiborod, Mikhail N.
    Univ Missouri Kansas City, St Lukes Mid Amer Heart Inst, Kansas City, MO USA;Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia.
    McGuire, Darren K.
    Univ Texas Southwestern Med Ctr Dallas, Dallas, TX 75390 USA.
    Harrington, Robert A.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA.
    Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI): a phase 3, placebo-controlled, randomised trial2019In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 394, no 10204, p. 1169-1180Article in journal (Refereed)
    Abstract [en]

    Background

    Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor.

    Methods

    The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria:a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population).

    Findings

    Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3.3 years (IQR 2.8-3.8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7.3%] of 5558 vs 480 [8.6%] of 5596; HR 0.85 [95% CI 0.74-0.97], p=0.013). The same effect was not observed in patients without PCI (p=0.76, p(interaction)=0.16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3.1%] with ticagrelor vs 183 (3.3%) with placebo; HR 0.96 [95% CI 0.78-1.18], p=0.68), as well as all-cause death (282 [5.1%] vs 323 [5.8%]; 0.88 [0.75-1.03], p=0.11). TIMI major bleeding occurred in 111 (2.0%) of 5536 patients receiving ticagrelor and 62 (1.1%) of 5564 patients receiving placebo (HR 2.03 [95% CI 1.48-2.76], p<0.0001), and fatal bleeding in 6 (0.1%) of 5536 patients with ticagrelor and 6 (0.1%) of 5564 with placebo (1.13 [0.36-3.50], p=0.83). Intracranial haemorrhage occurred in 33 (0.6%) and 31 (0.6%) patients (1.21 [0.74-1.97], p=0.45). Ticagrelor improved net clinical benefit:519/5558 (9.3%) versus 617/5596 (11.0%), HR=0.85, 95% CI 0.75-0.95, p=0.005, in contrast to patients without PCI where it did not, p(interaction)=0.012. Benefit was present irrespective of time from most recent PCI.

    Interpretation

    In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk.

  • 49.
    Bikdeli, Behnood
    et al.
    Harvard Med Sch, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA USA.;Harvard Med Sch, Brigham & Womens Hosp, Thrombosis Res Grp, Boston, MA USA.;Yale New Haven Hosp, Yale Ctr Outcomes Res & Evaluat, New Haven, CT USA..
    Erlinge, David
    Lund Univ, Lund, Sweden..
    Valgimigli, Marco
    Univ Bern, Univ Hosp Bern, Bern, Switzerland..
    Kastrati, Adnan
    Tech Univ, Deutsch Herzzentrum Munchen, Munich, Germany.;German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany..
    Han, Yaling
    Gen Hosp Northern Theater Command, Shenyang, Peoples R China..
    Steg, Philippe Gabriel
    Univ Paris Cite, French Alliance Cardiovasc Trials, Inst Natl Sante & Rech Med, Assistance Publ Hop Paris,U1148, Paris, France.;Imperial Coll, Royal Brompton Hosp, London, England..
    Stables, Rod H.
    Liverpool Heart & Chest Hosp, Liverpool, Merseyside, England.;Univ Liverpool, Liverpool, Merseyside, England..
    Mehran, Roxana
    Icahn Sch Med Mt Sinai, Zena & Michael A Wiener Cardiovasc Inst, New York, NY USA.;Cardiovasc Res Fdn, New York, NY USA..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Frigoli, Enrico
    Univ Bern, Univ Hosp Bern, Bern, Switzerland..
    Goldstein, Patrick
    Lille Univ Hosp, Lille, France..
    Li, Yi
    Gen Hosp Northern Theater Command, Shenyang, Peoples R China..
    Shahzad, Adeel
    Liverpool Heart & Chest Hosp, Liverpool, Merseyside, England.;Univ Liverpool, Liverpool, Merseyside, England..
    Schuepke, Stefanie
    Tech Univ, Deutsch Herzzentrum Munchen, Munich, Germany.;German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany..
    Mehdipoor, Ghazaleh
    Montefiore Med Ctr, Div Nucl Med, Dept Radiol, Bronx, NY USA..
    Chen, Shmuel
    New York Presbyterian Hosp, Weill Cornell Cornell Med Ctr, New York, NY USA..
    Redfors, Bjorn
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Crowley, Aaron
    Genesis Res, Hoboken, NJ USA..
    Zhou, Zhipeng
    Cardiovasc Res Fdn, New York, NY USA..
    Stone, Gregg W.
    Icahn Sch Med Mt Sinai, Zena & Michael A Wiener Cardiovasc Inst, New York, NY USA..
    Bivalirudin Versus Heparin During PCI in NSTEMI: Individual Patient Data Meta-Analysis of Large Randomized Trials2023In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 148, no 16, p. 1207-1219Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The benefit:risk profile of bivalirudin versus heparin anticoagulation in patients with non-ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) is uncertain. Study-level meta-analyses lack granularity to provide conclusive answers. We sought to compare the outcomes of bivalirudin and heparin in patients with non-ST-segment-elevation myocardial infarction undergoing PCI.

    METHODS: We performed an individual patient data meta-analysis of patients with non-ST-segment-elevation myocardial infarction in all 5 trials that randomized >= 1000 patients with any myocardial infarction undergoing PCI to bivalirudin versus heparin (MATRIX [Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox], VALIDATE-SWEDEHEART [Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial], ISAR-REACT 4 [Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 4], ACUITY [Acute Catheterization and Urgent Intervention Triage Strategy], and BRIGHT [Bivalirudin in Acute Myocardial Infarction vs Heparin and GPI Plus Heparin Trial]). The primary effectiveness and safety end points were 30-day all-cause mortality and serious bleeding.

    RESULTS: A total of 12155 patients were randomized: 6040 to bivalirudin (52.3% with a post-PCI bivalirudin infusion), and 6115 to heparin (53.2% with planned glycoprotein IIb/IIIa inhibitor use). Thirty-day mortality was not significantly different between bivalirudin and heparin (1.2% versus 1.1%; adjusted odds ratio, 1.24 [95% CI, 0.86-1.79]; P=0.25). Cardiac mortality, reinfarction, and stent thrombosis rates were also not significantly different. Bivalirudin reduced serious bleeding (both access site-related and non-access site-related) compared with heparin (3.3% versus 5.5%; adjusted odds ratio, 0.59; 95% CI, 0.48-0.72; P<0.0001). Outcomes were consistent regardless of use of a post-PCI bivalirudin infusion or routine lycoprotein IIb/IIIa inhibitor use with heparin and during 1-year follow-up.

    CONCLUSIONS: In patients with non-ST-segment-elevation myocardial infarction undergoing PCI, procedural anticoagulation with bivalirudin and heparin did not result in significantly different rates of mortality or ischemic events, including stent thrombosis and reinfarction. Bivalirudin reduced serious bleeding compared with heparin arising both from the access site and nonaccess sites.

  • 50.
    Bikdeli, Behnood
    et al.
    Columbia Univ, Dept Med, NewYork Presbyterian Hosp, Med Ctr,Div Cardiol, New York, NY USA;Yale Univ, Yale Sch Med, Ctr Outcomes Res & Evaluat, New Haven, CT USA;Cardiovasc Res Fdn, Clin Trials Ctr, New York, NY 10019 USA.
    McAndrew, Thomas
    Cardiovasc Res Fdn, Clin Trials Ctr, New York, NY 10019 USA.
    Crowley, Aaron
    Cardiovasc Res Fdn, Clin Trials Ctr, New York, NY 10019 USA.
    Chen, Shmuel
    Columbia Univ, Dept Med, NewYork Presbyterian Hosp, Med Ctr,Div Cardiol, New York, NY USA;Cardiovasc Res Fdn, Clin Trials Ctr, New York, NY 10019 USA.
    Mehdipoor, Ghazaleh
    Cardiovasc Res Fdn, Clin Trials Ctr, New York, NY 10019 USA.
    Redfors, Bjorn
    Columbia Univ, Dept Med, NewYork Presbyterian Hosp, Med Ctr,Div Cardiol, New York, NY USA;Cardiovasc Res Fdn, Clin Trials Ctr, New York, NY 10019 USA;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden.
    Liu, Yangbo
    Cardiovasc Res Fdn, Clin Trials Ctr, New York, NY 10019 USA.
    Zhang, Zixuan
    Cardiovasc Res Fdn, Clin Trials Ctr, New York, NY 10019 USA.
    Liu, Mengdan
    Cardiovasc Res Fdn, Clin Trials Ctr, New York, NY 10019 USA.
    Zhang, Yiran
    Cardiovasc Res Fdn, Clin Trials Ctr, New York, NY 10019 USA.
    Francese, Dominic P.
    Cardiovasc Res Fdn, Clin Trials Ctr, New York, NY 10019 USA.
    Erlinge, David
    Lund Univ, Dept Cardiol, Lund, Sweden.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Han, Yaling
    Gen Hosp Northern Theater Command, Dept Cardiol, Shenyang, Peoples R China.
    Li, Yi
    Gen Hosp Northern Theater Command, Dept Cardiol, Shenyang, Peoples R China.
    Kastrati, Adnan
    Tech Univ, Deutsch Herzzentrum Munchen, Dept Cardiol, Munich, Germany.
    Schuepke, Stefanie
    Tech Univ, Deutsch Herzzentrum Munchen, Dept Cardiol, Munich, Germany.
    Stables, Rod H.
    Liverpool Heart & Chest Hosp, Liverpool, Merseyside, England;Univ Liverpool, Liverpool, Merseyside, England.
    Shahzad, Adeel
    Liverpool Heart & Chest Hosp, Liverpool, Merseyside, England.
    Steg, Philippe Gabriel
    Hop Bichat Claude Bernard, Paris, France;Royal Brompton Hosp, Imperial Coll, London, England.
    Goldstein, Patrick
    Lille Univ Hosp, Lille, France.
    Frigoli, Enrico
    Univ Bern, Bern Univ Hosp, Dept Cardiol, Bern, Switzerland.
    Mehran, Roxana
    Cardiovasc Res Fdn, Clin Trials Ctr, New York, NY 10019 USA;Icahn Sch Med Mt Sinai, Zena & Michael A Wiener Cardiovasc Inst, New York, NY 10029 USA.
    Valgimigli, Marco
    Univ Bern, Bern Univ Hosp, Dept Cardiol, Bern, Switzerland.
    Stone, Gregg W.
    Cardiovasc Res Fdn, Clin Trials Ctr, New York, NY 10019 USA;Icahn Sch Med Mt Sinai, Zena & Michael A Wiener Cardiovasc Inst, New York, NY 10029 USA.
    Individual Patient Data Pooled Analysis of Randomized Trials of Bivalirudin versus Heparin in Acute Myocardial Infarction: Rationale and Methodology2020In: Thrombosis and Haemostasis, ISSN 0340-6245, E-ISSN 2567-689X, Vol. 120, no 2, p. 348-361Article in journal (Refereed)
    Abstract [en]

    Background

    Individual randomized controlled trials (RCTs) of periprocedural anticoagulation with bivalirudin versus heparin during percutaneous coronary intervention (PCI) have reported conflicting results. Study-level meta-analyses lack granularity to adjust for confounders, explore heterogeneity, or identify subgroups that may particularly benefit or be harmed.

    Objective

    To overcome these limitations, we sought to develop an individual patient-data pooled database of RCTs comparing bivalirudin versus heparin.

    Methods

    We conducted a systematic review to identify RCTs in which ≥1,000 patients with acute myocardial infarction (AMI) undergoing PCI were randomized to bivalirudin versus heparin.

    Results

    From 738 identified studies, 8 RCTs met the prespecified criteria. The principal investigators of each study agreed to provide patient-level data. The data were pooled and checked for accuracy against trial publications, with discrepancies addressed by consulting with the trialists. Consensus-based definitions were created to resolve differing antithrombotic, procedural, and outcome definitions. The project required 3.5 years to complete, and the final database includes 27,409 patients (13,346 randomized to bivalirudin and 14,063 randomized to heparin).

    Conclusion

    We have created a large individual patient database of bivalirudin versus heparin RCTs in patients with AMI undergoing PCI. This endeavor may help identify the optimal periprocedural anticoagulation regimen for patient groups with different relative risks of adverse ischemic versus bleeding events, including those with ST-segment and non-ST-segment elevation MI, radial versus femoral access, use of a prolonged bivalirudin infusion or glycoprotein inhibitors, and others. Adherence to standardized techniques and rigorous validation processes should increase confidence in the accuracy and robustness of the results.

    .

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