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  • 1.
    Aktaa, Suleman
    et al.
    Univ Leeds, Leeds Inst Cardiovasc & Metab Med, Leeds, W Yorkshire, England.;Univ Leeds, Leeds Inst Data Analyt, Leeds, W Yorkshire, England.;Leeds Teaching Hosp NHS Trust, Dept Cardiol, Leeds, W Yorkshire, England.
    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.
    Cleland, John G. F.
    Univ Glasgow, Glasgow Royal Infirm, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.;Univ Glasgow, Glasgow Royal Infirm, Glasgow Clin Trials Unit, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland.;Imperial Coll London, Natl Heart & Lung Inst, London, England.
    Coats, Andrew
    Univ Warwick, Coventry, W Midlands, England.;European Soc Cardiol, Heart Failure Assoc, Brussels, Belgium.
    Lund, Lars H.
    Karolinska Inst, Dept Med, Unit Cardiol, Stockholm, Sweden.;Karolinska Univ Hosp, Heart & Vasc Theme, Stockholm, Sweden.
    McDonagh, Theresa
    Kings Coll Hosp London, Dept Cardiol, Denmark Hill, London, England.;Kings Coll London, British Heart Fdn, Ctr Excellence, Sch Cardiovasc Med & Sci, London, England.
    Rosano, Giuseppe
    St Georges Hosp NHS Trust Univ London, Cardiovasc Clin Acad Grp, London, England.;IRCCS San Raffaele Pisana, Rome, Italy.
    Seferovic, Petar
    Univ Belgrade, Serbian Acad Sci & Arts, Fac Med, Heart Failure Ctr,Med Ctr, Belgrade, Serbia.
    Vasko, Peter
    Univ Hosp, Dept Cardiol, Linköping, Sweden.;SWEDEHEART Swedish Web Syst Enhancement & Dev Evi, Växjö, Sweden.;SwedeHF Swedish Heart Failure Registry, Växjö, Sweden.
    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. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Maggioni, Aldo P.
    Natl Assoc Hosp Cardiologists Res Ctr ANMCO, Florence, Italy.
    Casadei, Barbara
    Univ Oxford, NIHR Oxford Biomed Res Ctr, Div Cardiovasc Med, Oxford, England.
    Gale, Chris P.
    Univ Leeds, Leeds Inst Cardiovasc & Metab Med, Leeds, W Yorkshire, England.;Univ Leeds, Leeds Inst Data Analyt, Leeds, W Yorkshire, England.;Leeds Teaching Hosp NHS Trust, Dept Cardiol, Leeds, W Yorkshire, England.
    Data standards for heart failure: the European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart)2022In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 43, no 23, p. 2185-+Article in journal (Refereed)
    Abstract [en]

    Standardized data definitions are essential for assessing the quality of care and patient outcomes in observational studies and randomized controlled trials. The European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart) project of the European Society of Cardiology (ESC) aims to create contemporary pan-European data standards for cardiovascular diseases, including heart failure (HF). We followed the EuroHeart methodology for cardiovascular data standard development. A Working Group including experts in HF registries, representatives from the Heart Failure Association of the ESC, and the EuroHeart was formed. Using Embase and Medline (2016-21), we conducted a systematic review of the literature on data standards, registries, and trials to identify variables pertinent to HF. A modified Delphi method was used to reach a consensus on the final set of variables. For each variable, the Working Group developed data definitions and agreed on whether it was mandatory (Level 1) or additional (Level 2). In total, 84 Level 1 and 79 Level 2 variables were selected for nine domains of HF care. These variables were reviewed by an international Reference Group with the Level 1 variables providing the dataset for registration of patients with HF on the EuroHeart IT platform. By means of a structured process and interaction with international stakeholders, harmonized data standards for HF have been developed. In the context of the EuroHeart, this will facilitate quality improvement, international observational research, registry-based randomized trials, and post-marketing surveillance of devices and pharmacotherapies across Europe.

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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, J.
    et al.
    Duke Clin Res Inst, Durham, NC USA..
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lopes, R. D.
    Duke Clin Res Inst, Durham, NC USA..
    Hijazi, Ziad
    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 Univ, Dept Med Sci, Cardiol, Uppsala, Sweden.;Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden..
    Hohnloser, S. H.
    Goethe Univ Frankfurt, Div Cardiac Electrophysiol, D-60054 Frankfurt, Germany..
    Ezekowitz, J.
    Univ Alberta, Edmonton, AB, Canada..
    Halvorsen, S.
    Oslo Univ Hosp, Dept Cardiol, Oslo, Norway..
    Hanna, M.
    Bristol Myers Squibb Co, Princeton, NJ USA..
    Granger, C. B.
    Duke Clin Res Inst, Durham, NC USA..
    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.
    Stroke and bleeding outcomes with apixaban versus warfarin in patients with high creatinine, low body weight or high age receiving standard dose apixaban for stroke prevention in atrial fibrillation2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no Suppl. 1, p. 345-345Article in journal (Other academic)
  • 5. Alexander, John H
    et al.
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lopes, Renato D
    Hijazi, Ziad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hohnloser, Stefan H
    Ezekowitz, Justin A
    Halvorsen, Sigrun
    Hanna, Michael
    Commerford, Patrick
    Ruzyllo, Witold
    Huber, Kurt
    Al-Khatib, Sana M
    Granger, Christopher B
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Apixaban 5 mg Twice Daily and Clinical Outcomes in Patients With Atrial Fibrillation and Advanced Age, Low Body Weight, or High Creatinine: A Secondary Analysis of a Randomized Clinical Trial2016In: JAMA cardiology, ISSN 2380-6583, E-ISSN 2380-6591, Vol. 1, no 6, p. 673-681Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE: In the Apixaban for Reduction of Stroke and Other Thromboembolic Complications in Atrial Fibrillation (ARISTOTLE) trial, the standard dose of apixaban was 5 mg twice daily; patients with at least 2 dose-reduction criteria-80 years or older, weight 60 kg or less, and creatinine level 1.5 mg/dL or higher-received a reduced dose of apixaban of 2.5 mg twice daily. Little is known about patients with 1 dose-reduction criterion who received the 5 mg twice daily dose of apixaban.

    OBJECTIVE: To determine the frequency of 1 dose-reduction criterion and whether the effects of the 5 mg twice daily dose of apixaban on stroke or systemic embolism and bleeding varied among patients with 1 or no dose-reduction criteria.

    DESIGN, SETTING, AND PARTICIPANTS: Among 18 201 patients in the ARISTOTLE trial, 17 322 were included in this analysis. Annualized event rates of stroke or systemic embolism and major bleeding and hazard ratios (HRs) and 95% CIs were evaluated. Interactions between the effects of apixaban vs warfarin and the presence of 1 or no dose-reduction criteria were assessed. The first patient was enrolled in the ARISTOTLE trial on December 19, 2006, and follow-up was completed on January 30, 2011. Data were analyzed from January 2015 to May 30, 2016.

    MAIN OUTCOMES AND MEASURES: Analysis of major bleeding included events during study drug treatment. Analysis of stroke or systemic embolism was based on intention to treat.

    RESULTS: Of the patients with 1 or no dose-reduction criteria assigned to receive the 5 mg twice daily dose of apixaban or warfarin, 3966 had 1 dose-reduction criterion; these patients had higher rates of stroke or systemic embolism (HR, 1.47; 95% CI, 1.20-1.81) and major bleeding (HR, 1.89; 95% CI, 1.62-2.20) compared with those with no dose-reduction criteria (n = 13 356). The benefit of the 5 mg twice daily dose of apixaban (n = 8665) compared with warfarin (n = 8657) on stroke or systemic embolism in patients with 1 dose-reduction criterion (HR, 0.94; 95% CI, 0.66-1.32) and no dose-reduction criterion (HR, 0.77; 95% CI, 0.62-0.97) were similar (P for interaction = .36). Similarly, the benefit of 5 mg twice daily dose of apixaban compared with warfarin on major bleeding in patients with 1 dose-reduction criterion (HR, 0.68; 95% CI, 0.53-0.87) and no dose-reduction criterion (HR, 0.72; 95% CI, 0.60-0.86) were similar (P for interaction = .71). Similar patterns were seen for each dose-reduction criterion and across the spectrum of age, body weight, creatinine level, and creatinine clearance.

    CONCLUSIONS AND RELEVANCE: Patients with atrial fibrillation and isolated advanced age, low body weight, or renal dysfunction have a higher risk of stroke or systemic embolism and major bleeding but show consistent benefits with the 5 mg twice daily dose of apixaban vs warfarin compared with patients without these characteristics. The 5 mg twice daily dose of apixaban is safe, efficacious, and appropriate for patients with only 1 dose-reduction criterion.

    TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00412984.

  • 6. Alexander, John H.
    et al.
    Becker, Richard C.
    Bhatt, Deepak L.
    Cools, Frank
    Crea, Filippo
    Dellborg, Mikael
    Fox, Keith A. A.
    Goodman, Shaun G.
    Harrington, Robert A.
    Huber, Kurt
    Husted, Steen
    Lewis, Basil S.
    Lopez-Sendon, Jose
    Mohan, Puneet
    Montalescot, Gilles
    Ruda, Mikhail
    Ruzyllo, Witold
    Verheugt, Freek
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Apixaban, an oral, direct, selective factor Xa inhibitor, in combination with antiplatelet therapy after acute coronary syndrome: results of the Apixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) trial2009In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 119, no 22, p. 2877-2885Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: After an acute coronary syndrome, patients remain at risk of recurrent events. Apixaban, an oral direct factor Xa inhibitor, is a novel anticoagulant that may reduce these events but also poses a risk of bleeding. METHODS AND RESULTS: Apixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) was a phase 2, double-blind, placebo-controlled, dose-ranging study. Patients (n=1715) with recent ST-elevation or non-ST-elevation acute coronary syndrome were randomized to 6 months of placebo (n=611) or 1 of 4 doses of apixaban: 2.5 mg twice daily (n=317), 10 mg once daily (n=318), 10 mg twice daily (n=248), or 20 mg once daily (n=221). Nearly all patients received aspirin; 76% received clopidogrel. The primary outcome was International Society of Thrombosis and Hemostasis major or clinically relevant nonmajor bleeding. A secondary outcome was cardiovascular death, myocardial infarction, severe recurrent ischemia, or ischemic stroke. At the recommendation of the Data Monitoring Committee, the 2 higher-dose apixaban arms were discontinued because of excess total bleeding. Compared with placebo, apixaban 2.5 mg twice daily (hazard ratio, 1.78; 95% confidence interval, 0.91 to 3.48; P=0.09) and 10 mg once daily (hazard ratio, 2.45; 95% confidence interval, 1.31 to 4.61; P=0.005) resulted in a dose-dependent increase in major or clinically relevant nonmajor bleeding. Apixaban 2.5 mg twice daily (hazard ratio, 0.73; 95% confidence interval, 0.44 to 1.19; P=0.21) and 10 mg once daily (hazard ratio, 0.61; 95% confidence interval, 0.35 to 1.04; P=0.07) resulted in lower rates of ischemic events compared with placebo. The increase in bleeding was more pronounced and the reduction in ischemic events was less evident in patients taking aspirin plus clopidogrel than in those taking aspirin alone. CONCLUSIONS: We observed a dose-related increase in bleeding and a trend toward a reduction in ischemic events with the addition of apixaban to antiplatelet therapy in patients with recent acute coronary syndrome. The safety and efficacy of apixaban may vary depending on background antiplatelet therapy. Further testing of apixaban in patients at risk of recurrent ischemic events is warranted.

  • 7. Alexander, John H.
    et al.
    Levy, Elliott
    Lawrence, Jack
    Hanna, Michael
    Waclawski, Anthony P.
    Wang, Junyuan
    Califf, Robert M.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Granger, Christopher B.
    Documentation of study medication dispensing in a prospective large randomized clinical trial: Experiences from the ARISTOTLE Trial2013In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 166, no 3, p. 559-+Article in journal (Refereed)
    Abstract [en]

    Background In ARISTOTLE, apixaban resulted in a 21% reduction in stroke, a 31% reduction in major bleeding, and an 11% reduction in death. However, approval of apixaban was delayed to investigate a statement in the clinical study report that "7.3% of subjects in the apixaban group and 1.2% of subjects in the warfarin group received, at some point during the study, a container of the wrong type." Methods Rates of study medication dispensing error were characterized through reviews of study medication container tear-off labels in 6,520 participants from randomly selected study sites. The potential effect of dispensing errors on study outcomes was statistically simulated in sensitivity analyses in the overall population. Results The rate of medication dispensing error resulting in treatment error was 0.04%. Rates of participants receiving at least 1 incorrect container were 1.04% (34/3,273) in the apixaban group and 0.77% (25/3,247) in the warfarin group. Most of the originally reported errors were data entry errors in which the correct medication container was dispensed but the wrong container number was entered into the case report form. Sensitivity simulations in the overall trial population showed no meaningful effect of medication dispensing error on the main efficacy and safety outcomes. Conclusions Rates of medication dispensing error were low and balanced between treatment groups. The initially reported dispensing error rate was the result of data recording and data management errors and not true medication dispensing errors. These analyses confirm the previously reported results of ARISTOTLE.

  • 8. 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.

  • 9. Alexander, John H.
    et al.
    Lopes, Renato D.
    Thomas, Laine
    Alings, Marco
    Atar, Dan
    Aylward, Philip
    Goto, Shinya
    Hanna, Michael
    Huber, Kurt
    Husted, Steen
    Lewis, Basil S.
    McMurray, John J. V.
    Pais, Prem
    Pouleur, Hubert
    Steg, Philippe Gabriel
    Verheugt, Freek W. A.
    Wojdyla, Daniel M.
    Granger, Christopher B.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Apixaban vs. warfarin with concomitant aspirin in patients with atrial fibrillation: insights from the ARISTOTLE trial2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, no 4, p. 224-232Article in journal (Refereed)
    Abstract [en]

    Aims We assessed the effect of concomitant aspirin use on the efficacy and safety of apixaban compared with warfarin in patients with atrial fibrillation (AF). Methods and results In ARISTOTLE, 18 201 patients were randomized to apixaban 5 mg twice daily or warfarin. Concomitant aspirin use was left to the discretion of the treating physician. In this predefined analysis, simple and marginal structured models were used to adjust for baseline and time-dependent confounders associated with aspirin use. Outcome measures included stroke or systemic embolism, ischaemic stroke, myocardial infarction, mortality, major bleeding, haemorrhagic stroke, major or clinically relevant non-major bleeding, and any bleeding. On Day 1, 4434 (24%) patients were taking aspirin. Irrespective of concomitant aspirin use, apixaban reduced stroke or systemic embolism [with aspirin: apixaban 1.12% vs. warfarin 1.91, hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.39-0.85 vs. without aspirin: apixaban 1.11% vs. warfarin 1.32%, HR 0.84, 95% CI 0.66-1.07; P interaction = 0.10] and caused less major bleeding than warfarin (with aspirin: apixaban 3.10 vs. warfarin 3.92%, HR 0.77, 95% CI 0.60-0.99 vs. without aspirin: apixaban 1.82% vs. warfarin 2.78, HR without aspirin 0.65, 95% CI 0.55-0.78; P interaction = 0.29). Similar results were seen in the subgroups of patients with and without arterial vascular disease. Conclusion Apixaban had similar beneficial effects on stroke or systemic embolism and major bleeding compared with warfarin, irrespective of concomitant aspirin use.

  • 10. Alexander, John H.
    et al.
    Lopes, Renato D.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Apixaban after Acute Coronary Syndrome REPLY2011In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 365, no 19, p. 1844-1845Article in journal (Refereed)
  • 11. Alexander, Karen P
    et al.
    Brouwer, Marc A
    Mulder, Hillary
    Vinereanu, Dragos
    Lopes, Renato D
    Proietti, Marco
    Al-Khatib, Sana M
    Hijazi, Ziad
    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.
    Halvorsen, Sigrun
    Hylek, Elaine M
    Verheugt, Freek W A
    Alexander, John H
    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.
    Granger, Christopher B
    Outcomes of apixaban versus warfarin in patients with atrial fibrillation and multi-morbidity: Insights from the ARISTOTLE trial2019In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 208, p. 123-131, article id S0002-8703(18)30296-5Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Patients with atrial fibrillation (AF) often have multi-morbidity, defined as ≥3 comorbid conditions. Multi-morbidity is associated with polypharmacy, adverse events, and frailty potentially altering response to anticoagulation. We sought to describe the prevalence of multi-morbidity among older patients with AF and determine the association between multi-morbidity, clinical outcomes, and the efficacy and safety of apixaban compared with warfarin.

    METHODS: In this post-hoc subgroup analysis of the ARISTOTLE trial, we studied enrolled patients age ≥ 55 years (n = 16,800). Patients were categorized by the number of comorbid conditions at baseline: no multi-morbidity (0-2 comorbid conditions), moderate multi-morbidity (3-5 comorbid conditions), and high multi-morbidity (≥6 comorbid conditions). Association between multi-morbidity and clinical outcomes were analyzed by treatment with a median follow-up of 1.8 (1.3-2.3) years.

    RESULTS: Multi-morbidity was present in 64% (n = 10,713) of patients; 51% (n = 8491) had moderate multi-morbidity, 13% (n = 2222) had high multi-morbidity, and 36% (n = 6087) had no multi-morbidity. Compared with the no multi-morbidity group, the high multi-morbidity group was older (74 vs 69 years), took twice as many medications (10 vs 5), and had higher CHA2DS2-VASc scores (4.9 vs 2.7) (all P < .001). Adjusted rates per 100 patient-years for stroke/systemic embolism, death, and major bleeding increased with multi-morbidity (Reference no multi-morbidity; moderate multi-morbidity 1.42 [1.24-1.64] and high multi-morbidity 1.92 [1.59-2.31]), with no interaction in relation to efficacy or safety of apixaban.

    CONCLUSIONS: Multi-morbidity is prevalent among the population with AF; efficacy and safety of apixaban is preserved in this subgroup supporting extension of trial results to the most complex AF patients.

  • 12. Al-Faleh, Hussam
    et al.
    Fu, Yuling
    Wagner, Galen
    Goodman, Shaun
    Sgarbossa, Elena
    Granger, Christopher
    Van de Werf, Frans
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Armstrong, Paul W.
    Unraveling the spectrum of left bundle branch block in acute myocardial infarction: insights from the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT 2 and 3) trials2006In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 151, no 1, p. 10-5Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Left bundle branch block (LBBB) complicates the diagnosis of acute myocardial infarction (AMI). The Sgarbossa criteria were developed from GUSTO I to surmount this diagnostic challenge but have not been prospectively validated in a large population with presumed AMI. We evaluated their utility in the diagnosis and risk stratification of AMI patients in ASSENT 2 & 3. METHODS: Baseline electrocardiograms (ECG) of LBBB patients were scored using Sgarbossa's criteria (0-10) by 2 readers blinded to the CK/CK-MB data and clinical outcomes; 267 (1.2%) patients had LBBB on their baseline ECG. RESULTS: Among 253 LBBB patients with available peak CK/CK-MB data, 158 (62.5%) had peak CK/CK-MB levels > 2x ULN, thereby qualifying for the diagnosis of AMI. A Sgarbossa score of 3 was shown in 48.7% of LBBB patients with elevated CK/CK-MB versus in 12.6% of those without a CK/CK-MB rise (P < .001). Patients with higher Sgarbossa scores, ie, 3, had a higher mortality compared with those with a score < 3, (23.5% vs 7.7% at 30 days P < .001; and 33.7% vs 20.2% at 1 year, P < .001, respectively). CONCLUSIONS: Our findings validate the utility of Sgarbossa criteria for diagnosing AMI in the setting of LBBB. These criteria provide a simple and practical diagnostic approach to risk stratify this diagnostically challenging high-risk group and optimize risk-benefit of acute therapy.

  • 13. Alfredsson, Joakim
    et al.
    Clayton, Tim
    Damman, Peter
    Fox, Keith A. A.
    Fredriksson, Mats
    Lagerqvist, Bo
    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, 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.
    de Winter, Robbert J.
    Swahn, Eva
    Impact of an invasive strategy on 5 years outcome in men and women with non-ST-segment elevation acute coronary syndromes2014In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 168, no 4, p. 522-529Article in journal (Refereed)
    Abstract [en]

    Background A routine invasive (RI) strategy in non-ST-segment elevation acute coronary syndromes (NSTE ACS) has been associated with better outcome compared with a selective invasive (SI) strategy in men, but results in women have yielded disparate results. The aim of this study was to assess gender differences in long-term outcome with an SI compared with an RI strategy in NSTE ACS. Methods Individual patient data were obtained from the FRISC II trial, ICTUS trial, and RITA 3 trial for a collaborative meta-analysis. Results Men treated with an RI strategy had significantly lower rate of the primary outcome 5-year cardiovascular (CV) death/myocardial infarction (MI) compared with men treated with an SI strategy (15.6% vs 19.8%, P = .001); risk-adjusted hazards ratio (HR) 0.73 (95% CI 0.63-0.86). In contrast, there was little impact of an RI compared with an SI strategy on the primary outcome among women (16.5% vs 15.1%, P = .324); risk-adjusted HR 1.13 (95% CI 0.89-1.43), interaction P = .01. For the individual components of the primary outcome, a similar pattern was seen with lower rate of MI (adjusted HR 0.69, 95% CI 0.57-0.83) and CV death (adjusted HR 0.71, 95% CI 0.56-0.89) in men but without obvious difference in women in MI (adjusted HR 1.13, 95% CI 0.85-1.50) or CV death (adjusted HR 0.97, 95% CI 0.68-1.39). Conclusions In this meta-analysis comparing an SI and RI strategy, benefit from an RI strategy during long-term follow-up was confirmed in men. Conversely, in women, there was no evidence of benefit.

  • 14. Alfredsson, Joakim
    et al.
    Lindbäck, Johan
    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.
    Swahn, Eva
    Similar outcome with an invasive strategy in men and women with non-ST-elevation acute coronary syndromes: From the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART)2011In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 32, no 24, p. 3128-3136Article in journal (Refereed)
    Abstract [en]

    Aims

    To assess gender differences in outcome with an early invasive or non-invasive strategy in patients with non-ST-elevation acute coronary syndromes (NSTE ACS).

    Methods and results

    We included 46 455 patients [14 819 women (32%) and 31 636 men (68%)] from the SWEDEHEART register, with NSTE ACS, between 2000 and 2006, and followed them for 1 year. In the non-invasive strategy arm, the relative risk (RR) of death was (women vs. men) 1.02 [95% confidence interval (CI), 0.94-1.11] and in the invasive strategy arm 1.12 (95% CI, 0.96-1.29). After adjustment for baseline differences between the genders, with propensity score and discharge medication, there was a similar trend towards better outcome among women in both the early non-invasive cohort [RR 0.90 (95% CI, 0.82-0.99)] and the early invasive cohort [RR 0.90 (95% CI, 0.76-1.06)], although it did not reach statistical significance in the early invasive cohort. Results were similar with the combined endpoint death/myocardial infarction. An early invasive treatment was associated with a marked, and similar, mortality reduction in women [RR 0.46 (95% CI, 0.38-0.55)] and men [RR 0.45 (95% CI, 0.40-0.52)], without interaction with gender.

    Conclusion

    In this large cohort of patients with NSTE ACS, reflecting real-life management, women and men had similar and better outcome associated with an invasive strategy.

  • 15. Alfredsson, Joakim
    et al.
    Stenestrand, Ulf
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Swahn, Ewa
    Gender differences in management and outcome in Non-ST-Elevation Acute Coronary Syndrome2007In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 93, no 11, p. 1357-1362Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To study gender differences in management and outcome in patients with non-ST-elevation acute coronary syndrome. DESIGN, SETTING AND PATIENTS: Cohort study of 53 781 consecutive patients (37% women) from the Register of Information and Knowledge about Swedish Heart Intensive care Admissions (RIKS-HIA), with a diagnosis of either unstable angina pectoris or non-ST-elevation myocardial infarction. All patients were admitted to intensive coronary care units in Sweden, between 1998 and 2002, and followed for 1 year. MAIN OUTCOME MEASURES: Treatment intensity and in-hospital, 30-day and 1-year mortality. RESULTS: Women were older (73 vs 69 years, p<0.001) and more likely to have a history of hypertension and diabetes, but less likely to have a history of myocardial infarction or revascularisation. After adjustment, there were no major differences in acute pharmacological treatment or prophylactic medication at discharge. Revascularisation was, however, even after adjustment, performed more often in men (OR 1.15; 95% CI, 1.09 to 1.21). After adjustment, there was no significant difference in in-hospital (OR 1.03; 95% CI, 0.94 to 1.13) or 30-days (OR 1.07; 95% CI, 0.99 to 1.15) mortality, but at 1 year being male was associated with higher mortality (OR 1.12; 95% CI, 1.06 to 1.19). CONCLUSION: Although women are somewhat less intensively treated, especially regarding invasive procedures, after adjustment for differences in background characteristics, they have better long-term outcomes than men.

  • 16.
    Al-Khatib, Sana M.
    et al.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Mulder, Hillary
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Wojdyla, Daniel
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Lopes, Renato D.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Alexander, John H.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Hijazi, Ziad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Goto, Shinya
    Tokai Univ, Sch Med, Isehara, Kanagawa, Japan..
    Granger, Christopher B.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Apixaban Versus Warfarin in Patients With Atrial Fibrillation and Left Ventricular Hypertrophy: Insights From the ARISTOTLE Trial2021In: Circulation: Arrhythmia and Electrophysiology, ISSN 1941-3149, E-ISSN 1941-3084, Vol. 14, no 3, p. 359-361, article id e009614Article in journal (Other academic)
  • 17. Al-Khatib, Sana M.
    et al.
    Thomas, Laine
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lopes, Renato D.
    Gersh, Bernard
    Garcia, David
    Ezekowitz, Justin
    Alings, Marco
    Yang, Hongqui
    Alexander, John H.
    Flaker, Gregory
    Hanna, Michael
    Granger, Christopher B.
    Outcomes of apixaban vs. warfarin by type and duration of atrial fibrillation: results from the ARISTOTLE trial2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no 31, p. 2464-2471Article in journal (Refereed)
    Abstract [en]

    It is uncertain whether the benefit from apixaban varies by type and duration of atrial fibrillation (AF). A total of 18 201 patients with AF [2786 (15.3) with paroxysmal and 15 412 (84.7) with persistent or permanent] were randomized to apixaban or warfarin. In this pre-specified secondary analysis, we compared outcomes and treatment effect of apixaban vs. warfarin by AF type and duration. The primary efficacy endpoint was a composite of ischaemic or haemorrhagic stroke or systemic embolism. The secondary efficacy endpoint was all-cause mortality. There was a consistent reduction in stroke or systemic embolism (P for interaction 0.71), all-cause mortality (P for interaction 0.75), and major bleeding (P for interaction 0.50) with apixaban compared with warfarin for both AF types. Apixaban was superior to warfarin in all studied endpoints, regardless of AF duration at study entry (P for all interactions 0.13). The rate of stroke or systemic embolism was significantly higher in patients with persistent or permanent AF than patients with paroxysmal AF (1.52 vs. 0.98; P 0.003, adjusted P 0.015). There was also a trend towards higher mortality in patients with persistent or permanent AF (3.90 vs. 2.81; P 0.0002, adjusted P 0.066). The risks of stroke, mortality, and major bleeding were lower with apixaban than warfarin regardless of AF type and duration. Although the risk of stroke or systemic embolism was lower in paroxysmal than persistent or permanent AF, apixaban is an attractive alternative to warfarin in patients with AF and at least one other risk factor for stroke, regardless of the type or duration of AF.

  • 18.
    Al-Khatib, Sana M.
    et al.
    Duke Univ, Duke Clin Res Inst, Sch Med, Durham, NC USA..
    Wojdyla, Daniel M.
    Duke Univ, Duke Clin Res Inst, Sch Med, Durham, NC USA..
    Granger, Christopher B.
    Duke Univ, Duke Clin Res Inst, Sch Med, Durham, NC USA..
    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).
    Garcia, David A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Univ Washington, Div Hematol, Seattle, WA 98195 USA..
    Hijazi, Ziad
    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.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Alexander, John H.
    Duke Univ, Duke Clin Res Inst, Sch Med, Durham, NC USA..
    Vinereanu, Dragos
    Univ Med & Pharm Carol Davila, Univ & Emergency Hosp, Bucharest, Romania..
    Flaker, Gregory C.
    Univ Missouri, Div Cardiol, Columbia, MO USA..
    Hylek, Elaine M.
    Boston Univ, Sch Med, Boston, MA USA..
    Lopes, Renato D.
    Duke Univ, Duke Clin Res Inst, Sch Med, Durham, NC USA..
    Duration of Anticoagulation Interruption Before Invasive Procedures and Outcomes in Patients With Atrial Fibrillation: Insights From the ARISTOTLE Trial2022In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 146, no 12, p. 958-960Article in journal (Refereed)
  • 19.
    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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  • 20.
    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.

  • 21. Andersson, T.
    et al.
    Nagy, P.
    Niazi, M.
    Nylander, S.
    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.
    Impact of omeprazole (OME), esomeprazole (ESO) plus /- acetylsalicylic acid (ASA) and lansoprazole (LAN) on the pharmacodynamics (PD) and pharmacokinetics (PK) of clopidogrel in healthy volunteers2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no Suppl 1, p. 343-343Article in journal (Other academic)
  • 22. Andersson, Tommy
    et al.
    Nagy, Peter
    Niazi, Mohammad
    Nylander, Sven
    Galbraith, Hal
    Ranjan, Santosh
    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.
    Effect of Esomeprazole With/Without Acetylsalicylic Acid, Omeprazole and Lansoprazole on Pharmacokinetics and Pharmacodynamics of Clopidogrel in Healthy Volunteers2014In: American Journal of Cardiovascular Drugs, ISSN 1175-3277, E-ISSN 1179-187X, Vol. 14, no 3, p. 217-227Article in journal (Refereed)
    Abstract [en]

    The effect of proton pump inhibitors (PPIs) on the pharmacokinetics and pharmacodynamics of clopidogrel was assessed in two healthy volunteer crossover studies. Study 1: subjects received clopidogrel alone (300-mg loading dose, then 75 mg/day for 28 days) and two of three PPIs (omeprazole 80 mg, esomeprazole 40 mg or lansoprazole 60 mg) plus clopidogrel for 29 days in three treatment periods (randomized treatment sequence assignment). Study 2: subjects received clopidogrel alone (75 mg/day for 9 days) and clopidogrel alone for 4 days followed by clopidogrel plus fixed-combination esomeprazole 20 mg/low-dose acetylsalicylic acid (ASA) 81 mg for 5 days in two treatment periods (randomized treatment sequence assignment). Pharmacokinetic effects were estimated by measuring active metabolite of clopidogrel, and pharmacodynamic effects by inhibition of adenosine diphosphate (ADP)-induced platelet aggregation. There was a relative decrease of up to 50 % in exposure to the active metabolite of clopidogrel with the different PPIs (study 1), and close to 40 % with esomeprazole/low-dose ASA (study 2), compared with clopidogrel alone. There was an absolute decrease of up to 17 % in inhibition of ADP-induced platelet aggregation with co-administration of different PPIs, compared with clopidogrel alone; however, no differences in platelet inhibition were observed during co-administration with the esomeprazole/low-dose ASA fixed-dose combination. Omeprazole, esomeprazole and lansoprazole decreased systemic exposure to the active metabolite of clopidogrel in healthy volunteers, leading to modest decreases in its antiplatelet effect. However, no apparent differences in platelet inhibition were observed when esomeprazole was co-administered with low-dose ASA as a fixed-dose combination.

  • 23. Andreotti, Felicita
    et al.
    Rocca, Bianca
    Husted, Steen
    Ajjan, Ramzi A
    Ten Berg, Jurrien
    Cattaneo, Marco
    Collet, Jean-Philippe
    De Caterina, Raffaele
    Fox, Keith A A
    Halvorsen, Sigrun
    Huber, Kurt
    Hylek, Elaine M
    Lip, Gregory Y H
    Montalescot, Gilles
    Morais, Joao
    Patrono, Carlo
    Verheugt, Freek W A
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Weiss, Thomas W
    Storey, Robert F
    Antithrombotic therapy in the elderly: expert position paper of the European Society of Cardiology Working Group on Thrombosis2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no 46, p. 3238-+Article in journal (Refereed)
  • 24. Armaganijan, Luciana
    et al.
    Lopes, Renato
    Huang, Zhen
    Tricoci, Pierluigi
    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.
    Van de Werf, Frans
    Armstrong, Paul W.
    Aylward, Philip E.
    White, Harvey D.
    Moliterno, David J.
    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.
    Chen, Edmond
    Harrington, Robert A.
    Strony, John
    Mahaffey, Kenneth W.
    Efficacy and Safety of Vorapaxar in Elderly Patients With Non-ST-Segment Elevation Acute Coronary Syndrome: Insights From the TRACER Trial2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 22Article in journal (Other academic)
  • 25.
    Armaganijan, Luciana V.
    et al.
    Brazilian Clin Res Inst, Sao Paulo, Brazil..
    Alexander, Karen P.
    Duke Clin Res Inst, Durham, NC USA..
    Huang, Zhen
    Duke Clin Res Inst, Durham, NC USA..
    Tricoci, Pierluigi
    Duke Clin Res Inst, Durham, NC USA..
    Held, Claes
    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.
    Van de Werf, Frans
    Univ Hosp Leuven, Dept Cardiol, Leuven, Belgium..
    Armstrong, Paul W.
    Univ Alberta, Edmonton, AB, Canada..
    Aylward, Philip E.
    Flinders Univ & Med Ctr, South Australian Hlth & Med Res Inst, Adelaide, SA, Australia..
    White, Harvey D.
    Green Lane Cardiovasc Serv, Auckland, New Zealand..
    Moliterno, David J.
    Gill Heart Inst, Lexington, KY USA.;Univ Kentucky, Lexington, KY USA..
    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.
    Chen, Edmond
    Bayer HealthCare Pharmaceut Inc, Whippany, NJ USA..
    Harrington, Robert A.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    Strony, John
    Johnson & Johnson, New Brunswick, NJ USA..
    Mahaffey, Kenneth W.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    Lopes, Renato D.
    Duke Clin Res Inst, Durham, NC USA..
    Effect of age on efficacy and safety of vorapaxar in patients with non-ST-segment elevation acute coronary syndrome: Insights from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial2016In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 178, p. 176-184Article in journal (Refereed)
    Abstract [en]

    Background Antithrombotic therapy plays an important role in the treatment of non-ST-segment elevation acute coronary syndromes (NSTE ACS) but is associated with bleeding risk. Advanced age may modify the relationship between efficacy and safety. Methods Efficacy and safety of vorapaxar (a protease-activated receptor 1 antagonist) was analyzed across ages as a continuous and a categorical variable in the 12,944 patients with NSTE ACS enrolled in the TRACER trial. To evaluate the effect of age, Cox regression models were developed to estimate hazard ratios (HRs) with the adjustment of other baseline characteristics and randomized treatment for the primary efficacy composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization, and the primary safety composite of moderate or severe Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding. Results The median age of the population was 64 years (25th, 75th percentiles = 58, 71). Also, 1,791 patients (13.8%) were <= 54 years of age, 4,968 (38.4%) were between 55 and 64 years, 3,979 (30.7%) were between 65 and 74 years, and 2,206 (17.1%) were 75 years or older. Older patients had higher rates of hypertension, renal insufficiency, and previous stroke and worse Killip class. The oldest age group (>= 75 years) had substantially higher 2-year rates of the composite ischemic end point and moderate or severe GUSTO bleeding compared with the youngest age group (<= 54 years). The relationships between treatment assignment (vorapaxar vs placebo) and efficacy outcomes did not vary by age. For the primary efficacy end point, the HRs (95% CIs) comparing vorapaxar and placebo in the 4 age groups were as follows: 1.12 (0.88-1.43), 0.88 (0.76-1.02), 0.89 (0.76-1.04), and 0.88 (0.74-1.06), respectively (P value for interaction = .435). Similar to what was observed for efficacy outcomes, we did not observe any interaction between vorapaxar and age on bleeding outcomes. For the composite of moderate or severe bleeding according to the GUSTO classification, the HRs (95% CIs) comparing vorapaxar and placebo in the 4 age groups were 1.73 (0.89-3.34), 1.39 (1.04-1.86), 1.10 (0.85-1.42), and 1.73 (1.29-2.33), respectively (P value for interaction = .574). Conclusion Older patients had a greater risk for ischemic and bleeding events; however, the efficacy and safety of vorapaxar in NSTE ACS were not significantly influenced by age.

  • 26. Armstrong, Paul W.
    et al.
    Chang, Wei-Ching
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Goldstein, Patrick
    Granger, Christopher B.
    Bogaerts, Kris
    Danays, Thierry
    Van de Werf, Frans
    Efficacy and safety of unfractionated heparin versus enoxaparin: a pooled analysis of ASSENT-3 and -3 PLUS data2006In: CMJA. Canadian Medical Association Journal. Onlineutg. Med tittel: ECMAJ. ISSN 1488-2329, ISSN 0820-3946, E-ISSN 1488-2329, Vol. 174, no 10, p. 1421-1426Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The optimal antithrombotic therapy to accompany tenecteplase in cases of acute ST-segment elevation myocardial infarction (STEMI) remains unclear. We undertook a prespecified pooled analysis of data from the ASSENT-3 and ASSENT-3 PLUS trials. METHODS: We created a combined database of the 2040 and 818 patients who received enoxaparin in ASSENT-3 and ASSENT-3 PLUS, respectively, and compared them with the 2038 and 821 patients who received unfractionated heparin. RESULTS: The efficacy end point (a composite of 30-day mortality, reinfarction or refractory ischemia) was 12.2% with enoxaparin versus 16.0% with unfractionated heparin (p < 0.001); the combined end point of efficacy plus safety (a composite of 30-day mortality, reinfarction, refractory ischemia, intracranial hemorrhage [ICH] or major systemic bleeding) was 15.0% versus 18.0%, respectively (p = 0.003) [corrected] The 1049 patients urgently revascularized had greater benefit from enoxaparin (15.4% v. 10.1%, p = 0.013), yet the excess in major systemic bleeding evident with enoxaparin (3.3% v. 2.4%, p = 0.01) was largely confined to the 3492 patients without or before revascularization. Although ICH rates in the groups were similar (1.3% v. 0.9%, p = 0.26), an excess of ICH occurred among those administered enoxaparin during the ASSENT-3 PLUS trial (6.7% v. 0.8%, p = 0.013), especially among women over 75 years of age. INTERPRETATION: These data demonstrated the benefit of enoxaparin used in conjunction with tenecteplase, but raised caution about its prehospital use to treat STEMI in elderly women.

  • 27. 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.

  • 28. Armstrong, Paul W
    et al.
    Wagner, Galen
    Goodman, Shaun G
    Van de Werf, Frans
    Granger, Christopher
    Wallentin, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Fu, Yuling
    ST segment resolution in ASSENT 3: insights into the role of three different treatment strategies for acute myocardial infarction.2003In: Eur Heart J, ISSN 0195-668X, Vol. 24, no 16, p. 1515-22Article in journal (Refereed)
  • 29. 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. 

  • 30.
    Arnetz, Judith E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Winblad, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research.
    Höglund, Anna T.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Spångberg, Kalle
    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.
    Wang, Yun
    Ager, Joel
    Arnetz, Bengt B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Is patient involvement during hospitalization for acute myocardial infarction associated with post-discharge treatment outcome?: an exploratory study2010In: Health Expectations, ISSN 1369-6513, E-ISSN 1369-7625, Vol. 13, no 3, p. 298-311Article in journal (Refereed)
    Abstract [en]

    Objective To investigate whether patient involvement during hospitalization for acute myocardial infarction (MI) was associated with health and behavioural outcomes 6–10 weeks after hospital discharge.

    Background Patient involvement has been associated with improved health outcomes in chronic disease, but less research has focused on the effects of patient involvement in acute conditions, such as MI.

    Design Self-administered questionnaire study. Questionnaire results were run against medical outcome data in a national database of cardiac patients.

    Setting and participants Cardiac patients (n = 591) on their first follow-up visit after hospitalization for MI at 11 Swedish hospitals.

    Main outcome measures Patient ratings of three questionnaire scales related to involvement; cardiovascular symptoms, medication compliance, participation in cardiac rehabilitation, and achievement of secondary preventive goals.

    Results More positive patient ratings of involvement were significantly associated with fewer cardiovascular symptoms 6–10 weeks after hospital discharge. In contrast, patients who attended cardiac rehabilitation and achieved the goals for smoking cessation and systolic blood pressure were significantly less satisfied with their involvement. No association was found between involvement ratings and medication compliance.

    Conclusion This study represents a first attempt to examine associations between patient involvement in the acute phase of illness and short-term health outcomes. Some significant associations between involvement and health and behavioural outcomes after acute MI were found. However, higher involvement ratings were not consistently associated with more desirable outcomes, and involvement during hospitalization was not associated with MI patient health and behaviour 6–10 weeks after hospital discharge to the extent hypothesized.

  • 31. 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.

  • 32.
    Attelind, Sofia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Hallberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Wadelius, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Hamberg, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    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, Coagulation and inflammation science.
    Granger, Christopher B.
    Duke Med, Duke Clin Res Inst, Durham, NC USA..
    Lopes, Renato D.
    Duke Med, Duke Clin Res Inst, Durham, NC USA..
    Alexander, John H.
    Duke Med, Duke Clin Res Inst, Durham, NC USA..
    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).
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Genetic determinants of apixaban plasma levels and their relationship to bleeding and thromboembolic events2022In: Frontiers in Genetics, E-ISSN 1664-8021, Vol. 13, article id 982955Article in journal (Refereed)
    Abstract [en]

    Apixaban is a direct oral anticoagulant, a factor Xa inhibitor, used for the prevention of ischemic stroke in patients with atrial fibrillation. Despite using recommended dosing a few patients might still experience bleeding or lack of efficacy that might be related to inappropriate drug exposure. We conducted a genome-wide association study using data from 1,325 participants in the pivotal phase three trial of apixaban with the aim to identify genetic factors affecting the pharmacokinetics of apixaban. A candidate gene analysis was also performed for pre-specified variants in ABCB1, ABCG2, CYP3A4, CYP3A5, and SULT1A1, with a subsequent analysis of all available polymorphisms within the candidate genes. Significant findings were further evaluated to assess a potential association with clinical outcome such as bleeding or thromboembolic events. No variant was consistently associated with an altered apixaban exposure on a genome-wide level. The candidate gene analyses showed a statistically significant association with a well-known variant in the drug transporter gene ABCG2 (c.421G > T, rs2231142). Patients carrying this variant had a higher exposure to apixaban [area under the curve (AUC), beta = 151 (95% CI 59-243), p = 0.001]. On average, heterozygotes displayed a 5% increase of AUC and homozygotes a 17% increase of AUC, compared with homozygotes for the wild-type allele. Bleeding or thromboembolic events were not significantly associated with ABCG2 rs2231142. This large genome-wide study demonstrates that genetic variation in the drug transporter gene ABCG2 is associated with the pharmacokinetics of apixaban. However, the influence of this finding on drug exposure was small, and further studies are needed to better understand whether it is of relevance for ischemic and bleeding events.

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  • 33.
    Aulin, Julia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hijazi, Ziad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Gersh, B. J.
    Hanna, M.
    Horowitz, J. D.
    Hylek, E. M.
    Lopes, R. D.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science. 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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Interleukin-6 and C-reactive protein and risk for cardiovascular events and death in anticoagulated patients with atrial fibrillation2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, p. 1115-1116Article in journal (Refereed)
  • 34.
    Aulin, Julia
    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.
    Hijazi, Ziad
    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).
    Alexander, John H.
    Duke Clin Res Inst, Duke Hlth, Durham, NC USA..
    Gersh, Bernard J.
    Mayo Clin, Coll Med & Sci, Rochester, MN USA..
    Granger, Christopher B.
    Duke Clin Res Inst, Duke Hlth, Durham, NC USA..
    Hanna, Michael
    Bristol Myers Squibb, Princeton, NJ USA..
    Horowitz, John
    Univ Adelaide, Basil Hetzel Inst, Adelaide, SA, Australia..
    Lopes, Renato D.
    Duke Clin Res Inst, Duke Hlth, Durham, NC USA..
    McMurray, John J. V.
    Univ Glasgow, BHF Cardiovasc Res Ctr, Glasgow, Scotland..
    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, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    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).
    Biomarkers and heart failure events in patients with atrial fibrillation in the ARISTOTLE trial evaluated by a multi-state model2022In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 251, p. 13-24Article in journal (Refereed)
    Abstract [en]

    Background

    Atrial fibrillation (AF) and heart failure (HF) often coexist. We investigated the prognostic impact of biomarkers on the development of HF and death in patients with AF and different left ventricular systolic function considering the influence of competing events.

    Methods

    The study included 11,818 patients with AF from the ARISTOTLE trial who at entry had information on history of HF, an estimate of left ventricular function and plasma samples for determination of biomarkers representing cardiorenal dysfunction (NT-proBNP, troponin T, cystatin C) and inflammation (GDF-15, IL-6, CRP). Patients were categorized into: (I) HF with reduced ejection fraction (HFrEF, n = 2,048), (II) HF with preserved ejection fraction (HFpEF, n = 2,520), and (III) No HF (n = 7,250). Biomarker associations with HF hospitalization and death were analyzed using a multi-state model accounting also for repeated events.

    Results

    Baseline levels of NT-proBNP, troponin T, cystatin C, GDF-15, IL-6, and CRP were highest in HFrEF and lowest in No HF. During median 1.9 years follow-up, 546 patients were hospitalized at least once for HF and 819 died. Higher levels of all investigated biomarkers were associated with both outcomes (all P < .0001), with highest event rates in HFrEF and lowest in No HF. The associations remained after adjustments and were more pronounced for first than for recurrent events.

    Conclusions

    In anticoagulated patients with AF, biomarkers indicating cardiorenal dysfunction and inflammation improve the identification of patients at risk of developing HF or worsening of already existing HF. These biomarkers might be useful for targeting novel HF therapies in patients with AF.

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  • 35.
    Aulin, Julia
    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, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Hijazi, Ziad
    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.
    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.
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Alexander, John H
    Connolly, Stuart J
    Ezekowitz, Michael D
    Gersh, Bernard J
    Granger, Christopher B
    Horowitz, John
    Hylek, Elaine M
    Lopes, Renato D
    Yusuf, Salim
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Oldgren, Jonas
    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.
    Serial measurement of interleukin-6 and risk of mortality in anticoagulated patients with atrial fibrillation: Insights from ARISTOTLE and RE-LY trials.2020In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 18, no 9, p. 2287-2295Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The inflammatory biomarker interleukin-6 (IL-6) is associated with mortality in atrial fibrillation (AF).

    OBJECTIVE: To investigate if repeated IL-6 measurements improve the prognostication for stroke or systemic embolism, major bleeding, and mortality in anticoagulated patients with AF.

    METHODS: IL-6 levels by ELISA were measured at study entry and at 2 months in 4830 patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial with 1.8 years median follow-up. In the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial, IL-6 was measured at study entry, 3, 6, and 12 months in 2559 patients with 2.0 years median follow-up. Associations between a second IL-6 measurement and outcomes, adjusted for baseline IL-6, clinical variables, and other cardiovascular biomarkers, were analyzed by Cox regression.

    RESULTS: Median IL-6 levels were 2.0 ng/L (interquartile range [IQR] 1.30-3.20) and 2.10 ng/L (IQR 1.40-3.40) at the two time-points in ARISTOTLE, and, in RE-LY, 2.5 ng/L (IQR 1.6-4.3), 2.5 ng/L (IQR 1.6-4.2), 2.4 ng/L (IQR 1.6, 3.9), and 2.4 ng/L (IQR 1.5, 3.9), respectively. IL-6 was associated with mortality; hazard ratios per 50% higher IL-6 at 2 or 3 months, respectively, were 1.32 (95% confidence interval, 1.23-1.41; P < .0001) in ARISTOTLE, and 1.11 (1.01-1.22, P = .0290) in RE-LY; with improved C index from 0.74 to 0.76 in ARISTOTLE, but not in the smaller RE-LY cohort. There were no consistent associations with second IL-6 and stroke or systemic embolism, or major bleeding.

    CONCLUSIONS: Persistent systemic inflammatory activity, assessed by repeated IL-6 measurements, is associated with mortality independent of established clinical risk factors and other strong cardiovascular biomarkers in anticoagulated patients with AF.

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  • 36.
    Aulin, Julia
    et al.
    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, Coagulation and inflammation science.
    Hijazi, Ziad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ezekowitz, Michael D.
    Lankenau Inst Med Res, Wynnewood, PA USA.;Ctr Heart, Wynnewood, PA USA..
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Connolly, Stuart J.
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    Huber, Kurt
    Dept Internal Med Cardiol & Emergency Med 3, Vienna, Austria..
    Reilly, Paul A.
    Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA..
    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.
    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.
    Interleukin-6 and C-reactive protein and risk for death and cardiovascular events in patients with atrial fibrillation2015In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 170, no 6, p. 1151-1160Article in journal (Refereed)
    Abstract [en]

    Background Inflammation has been associated with cardiovascular disease and the burden of atrial fibrillation (AF). In this study we evaluate inflammatory biomarkers and future cardiovascular events in AF patients in the RE-LY study. Methods Interleukin-6 (IL-6), C-reactive protein (CRP) (n = 6,187), and fibrinogen (n = 4,893) were analyzed at randomization; outcomes were evaluated by Cox models and C-statistics. Results Adjusted for clinical risk factors IL-6 was independently associated with stroke or systemic embolism (P =.0041), major bleedings (P =.0001), vascular death (P<.0001), and a composite thromboembolic outcome (ischemic stroke, systemic embolism, myocardial infarction, pulmonary embolism and vascular death) (P<.0001). CRP was independently related to myocardial infarction (P =.0047), vascular death (P =.0004), and the composite thromboembolic outcome (P =.0001). When further adjusted for cardiac (troponin andN-terminal fragment B-type natriuretic peptide [NT-proBNP]) and renal (cystatin-C) biomarkers on top of clinical risk factors IL-6 remained significantly related to vascular death (P<.0001), major bleeding (P<.0170) and the composite thromboembolic outcome (P<.0001), and CRP to myocardial infarction (.0104). Fibrinogen was not associated with any outcome. C-index for stroke or systemic embolism increased from 0.615 to 0.642 (P =.0017) when adding IL-6 to the clinically used CHA(2)DS(2)-VASc risk score with net reclassification improvement of 28%. Conclusion In patients with AF, IL-6 is related to higher risk of stroke and major bleeding, and both markers are related to higher risk of vascular death and the composite of thromboembolic events independent of clinical risk factors. Adjustment for cardiovascular biomarkers attenuated the prognostic value, although IL-6 remained related to mortality, the composite of thromboembolic events, and major bleeding, and CRP to myocardial infarction.

  • 37. Aviles, Ronnier J
    et al.
    Askari, Arman T
    Lindahl, Bertil
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Wallentin, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Jia, Gang
    Ohman, E Magnus
    Mahaffey, Kenneth W
    Newby, L Kristin
    Califf, Robert M
    Simoons, Maarten L
    Topol, Eric J
    Berger, Peter
    Lauer, Michael S
    Troponin T levels in patients with acute coronary syndromes, with or without renal dysfunction.2002In: N Engl J Med, ISSN 1533-4406, Vol. 346, no 26, p. 2047-52Article in journal (Refereed)
  • 38. Bagai, Akshay
    et al.
    Huang, Zhen
    Lokhnygina, Yuliya
    Harrington, Robert A.
    Armstrong, Paul W.
    Strony, John
    Chen, Edmond
    White, Harvey D.
    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.
    Van de Werf, Frans
    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.
    Tricoci, Pierluigi
    Mahaffey, Kenneth W.
    Differential Prognostic Implications of Peak Troponin Level in Acute Coronary Syndrome Treated With and Without Revascularization2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 22Article in journal (Other academic)
  • 39. Bagai, Akshay
    et al.
    Huang, Zhen
    Lokhnygina, Yuliya
    Harrington, Robert A
    Armstrong, Paul W
    Strony, John
    White, Harvey D
    Leonardi, Sergio
    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.
    Van de Werf, Frans
    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.
    Tricoci, Pierluigi
    Mahaffey, Kenneth W
    Magnitude of troponin elevation and long-term clinical outcomes in acute coronary syndrome patients treated with and without revascularization.2015In: Circulation. Cardiovascular Interventions, ISSN 1941-7640, E-ISSN 1941-7632, Vol. 8, no 6, article id e002314Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In patients with non-ST-segment-elevation acute coronary syndrome (NSTE ACS), elevated troponin levels identify patients at high risk for adverse outcomes; however, it is unknown whether the magnitude of troponin elevation during hospitalization remains predictive of subsequent events in patients undergoing coronary revascularization.

    METHODS AND RESULTS: We studied 12 635 patients with NSTE ACS in the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) study with at least 1 troponin measurement during index hospitalization. Cox proportional hazards regression was used to examine the relationship between peak troponin level (standardized as the ratio of peak troponin value measured during hospitalization and local laboratory upper reference limit [URL]) and revascularization on all-cause mortality at 2 years. Revascularization (percutaneous coronary intervention or coronary artery bypass graft) was performed during index hospitalization in 8586 patients (68.0%); revascularized patients had higher peak troponin ratios (median, 23 versus 9.5× URL). Among patients that did not undergo revascularization, the mortality rate at 2 years increased in a curvilinear fashion with increasing levels of peak troponin. In contrast, the mortality rate at 2 years remained constant irrespective of peak troponin levels among revascularized patients (P for interaction=0.004). This relationship was unchanged after multivariable adjustment.

    CONCLUSIONS: There is a differential relationship between the magnitude of troponin elevation and long-term mortality in ACS patients treated with and without revascularization. Although prognostically important in patients treated without revascularization, the prognostic implications of peak troponin level seem to be minimal in revascularized patients.

  • 40.
    Bahit, M. C.
    et al.
    INECO Neurociencias, Rosario, Santa Fe, Argentina..
    Lopes, R. D.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    Wojdyla, D. M.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    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.
    Hanna, M.
    Bristol Myers Squibb Co, Princeton, NJ USA..
    Vinereanu, D.
    Univ Med & Pharm Carol Davila, Bucharest, Romania..
    Goto, S.
    Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan..
    Alexander, J. H.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    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.
    Granger, C. B.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    Less non-major bleeding with apixaban versus warfarin among patients with atrial fibrillation: insights from the ARISTOTLE trial2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no Suppl. 1, p. 338-339Article in journal (Other academic)
  • 41.
    Bahit, M. Cecilia
    et al.
    INECO Neurociencias Orono, Rosario, Santa Fe, Argentina.
    Granger, Christopher B.
    Duke Clin Res Inst, 200 West Morris St, Durham, NC 27701 USA.
    Alexander, John H.
    Duke Clin Res Inst, 200 West Morris St, Durham, NC 27701 USA.
    Mulder, Hillary
    Duke Clin Res Inst, 200 West Morris St, Durham, NC 27701 USA.
    Wojdyla, Daniel M.
    Duke Clin Res Inst, 200 West Morris St, Durham, NC 27701 USA.
    Hanna, Michael
    Bristol Myers Squibb, Princeton, NJ USA.
    Goto, Shinya
    Tokai Univ, Sch Med, Isehara, Kanagawa, Japan.
    Xavier, Denis
    St Johns Med Coll, Bangalore, Karnataka, India.
    Verheugt, Freek W. A.
    OLVG, Dept Cardiol, Amsterdam, Netherlands.
    Lanas, Fernando
    Univ La Frontera, Temuco, Chile.
    Hijazi, Ziad
    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.
    Lopes, Renato D.
    Duke Clin Res Inst, 200 West Morris St, Durham, NC 27701 USA.
    Regional variation in clinical characteristics and outcomes in patients with atrial fibrillation: Findings from the ARISTOTLE trial2020In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 302, p. 53-58Article in journal (Refereed)
    Abstract [en]

    Background: Variation in patient characteristics and practice patterns may influence outcomes at a regional level.

    Methods: We assessed differences in demographics, practice patterns, outcomes, and the effect of apixaban compared with warfarin in ARISTOTLE (n = 18,201) by prespecified regions: North America, Latin America, Europe, and Asia Pacific. The primary outcomes were stroke/systemic embolism and major bleeding.

    Results: Compared with other regions, patients from Asia Pacific were younger, more women were enrolled in Latin America. Coronary artery disease was more prevalent in Europe and Asia Pacific had the highest rate of prior stroke and renal impairment. Over 50% of patients in North America were taking >= 9 drugs at randomization, compared with 10% in Latin America. North America had the highest rates of temporary study drug discontinuation and procedures. Time in therapeutic range (INR 2.0-3.0) on warfarin was highest in North America and lowest in Asia Pacific. After adjustment and compared with Europe, patients in Asia Pacific had 2-fold higher risk of stroke/systemic embolism and 3-fold higher risk of intracranial hemorrhage. Patients in Latin America had 2-fold increased risk of all-cause death compared with Europe. The benefits of apixaban compared with war-farin were consistent across regions; there was a pronounced reduction in major bleeding in patients from Asia Pacific compared with other regions (p-interaction = 0.03).

    Conclusions: Patients with AF enrolled in prespecified regions in ARISTOTLE had differences in clinical baseline characteristics and practice patterns. After adjustment, patients in Asia Pacific and Latin America had worse outcomes than patients from other regions. The relative benefits of apixaban compared with warfarin were consistent across regions with an even greater treatment effect in the reduction of bleeding in patients from Asia Pacific. 

  • 42.
    Bahit, M. Cecilia
    et al.
    INECO, Neurociencias Orono Rosario, Santa Fe, NM, Argentina..
    Lopes, Renato D.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Wojdyla, Daniel M.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hanna, Michael
    Bristol Myers Squibb, Princeton, NJ USA..
    Vinereanu, Dragos
    Univ Med & Pharm Carol Davila, Bucharest, Romania..
    Hylek, Elaine M.
    Boston Univ, Med Ctr, Boston, MA USA..
    Verheugt, Freek
    Onze Lieve Vrouwe Gasthuis OLVG, Heartctr, Amsterdam, Netherlands..
    Goto, Shinya
    Tokai Univ, Sch Med, Isehara, Kanagawa, Japan..
    Alexander, John H.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Granger, Christopher B.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Non-major bleeding with apixaban versus warfarin in patients with atrial fibrillation2017In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 103, no 8, p. 623-628Article in journal (Refereed)
    Abstract [en]

    Objective We describe the incidence, location and management of non-major bleeding, and assess the association between non-major bleeding and clinical outcomes in patients with atrial fibrillation (AF) receiving anticoagulation therapy enrolled in Apixaban for Reduction in Stroke and other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE). Methods We included patients who received >= 1 dose of study drug (n= 18 140). Non-major bleeding was defined as the first bleeding event considered to be clinically relevant non-major (CRNM) or minor bleeding, and not preceded by a major bleeding event. Results Non-major bleeding was three times more common than major bleeding (12.1% vs 3.8%). Like major bleeding, non-major bleeding was less frequent with apixaban (6.4 per 100 patient-years) than warfarin (9.4 per 100 patient-years) (adjusted HR 0.69, 95% CI 0.63 to 0.75). The most frequent sites of non-major bleeding were haematuria (16.4%), epistaxis (14.8%), gastrointestinal (13.3%), haematoma (11.5%) and bruising/ecchymosis (10.1%). Medical or surgical intervention was similar among patients with non-major bleeding on warfarin versus apixaban (24.7% vs 24.5%). A change in antithrombotic therapy (58.6% vs 50.0%) and permanent study drug discontinuation (5.1% (61) vs 3.6% (30), p=0.10) was numerically higher with warfarin than apixaban. CRNM bleeding was independently associated with an increased risk of overall death (adjusted HR 1.70, 95% CI 1.32 to 2.18) and subsequent major bleeding (adjusted HR 2.18, 95% CI 1.56 to 3.04). Conclusions In ARISTOTLE, non-major bleeding was common and substantially less frequent with apixaban than with warfarin. CRNM bleeding was independently associated with a higher risk of death and subsequent major bleeding. Our results highlight the importance of any severity of bleeding in patients with AF treated with anticoagulation therapy and suggest that non-major bleeding, including minor bleeding, might not be minor.

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  • 43. Bahit, Maria Cecilia
    et al.
    Granger, Christopher B
    Wallentin, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Persistence of the prothrombotic state after acute coronary syndromes: implications for treatment.2002In: Am Heart J, ISSN 1097-6744, Vol. 143, no 2, p. 205-16Article in journal (Refereed)
  • 44. 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)
  • 45. Bassand, Jean-Pierre
    et al.
    Afzal, Rizwan
    Eikelboom, John
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Peters, Ron
    Budaj, Andrzej
    Fox, Keith A. A.
    Joyner, Campbell D.
    Chrolavicius, Susan
    Granger, Christopher B.
    Mehta, Shamir
    Yusuf, Salim
    Relationship between baseline haemoglobin and major bleeding complications in acute coronary syndromes2010In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 31, no 1, p. 50-58Article in journal (Refereed)
    Abstract [en]

    AIMS: In patients with acute coronary syndromes (ACS), the negative impact of baseline haemoglobin levels on ischaemic events, particularly death, is well established, but the association with bleeding risk is less well studied. The aim of this study was to assess the impact of baseline haemoglobin levels on major bleeding complications. METHODS AND RESULTS: Pooled analysis of OASIS 5 and 6 data involving 32 170 patients with ACS with and without ST-segment elevation was performed. The association between baseline haemoglobin and major bleeding or ischaemic events was examined using multiple regression model. MAIN OUTCOME MEASURES: were 30-day rates of major bleeding, death, and death/myocardial infarction (MI) analysed according to baseline haemoglobin levels. Baseline haemoglobin level independently predicted the risk of overall, procedure-related, and non-procedure-related major bleedings at 30 days [odds ratio (OR) 0.94, 95% CI 0.90-0.98; OR 0.94, 95% CI 0.90-0.99; and OR 0.89, 95% CI 0.83-0.95, respectively, per 1 g/dL haemoglobin increment above 10 g/dL]. In addition, a curvilinear relationship between baseline haemoglobin levels and death at 30 days was observed with a 6% decrease in the risk for every 1 g/dL haemoglobin increment above 10 g/dL up to 15.9 g/dL (OR 0.94, 95% CI 0.90-0.98) and a 19% increase above this value (OR 1.19, 95% CI, 0.98-1.43). A similar relationship for the composite outcome of death/MI was observed. CONCLUSION: A low baseline haemoglobin level is an independent predictor of the risk of major bleeding in ACS as well as of the risk of death and death and MI. Among other predictors of bleeding risk, baseline haemoglobin should be taken into account in patients presenting with ACS. Clinical trial registration: ClinicalTrials.gov number, NCT00139815. http://clinicaltrials.gov/ct2/show/NCT00139815?term=NCT00139815&rank=1.

  • 46. Bassand, Jean-Pierre
    et al.
    Hamm, Christian W
    Ardissino, Diego
    Boersma, Eric
    Budaj, Andrzej
    Fernández-Avilés, Francisco
    Fox, Keith A A
    Hasdai, David
    Ohman, E Magnus
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Wijns, William
    Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes2007In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 28, no 13, p. 1598-1660Article in journal (Refereed)
  • 47. Bassand, Jean-Pierre
    et al.
    Hamm, Christian W
    Ardissino, Diego
    Boersma, Eric
    Budaj, Andrzej
    Fernández-Avilés, Francisco
    Fox, Keith Aa
    Hasdai, David
    Ohman, E Magnus
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wijns, William
    Guía de Práctica Clínica para el diagnóstico y tratamiento del síndrome coronario agudo sin elevación del segmento ST2007In: Revista Española de Cardiología, ISSN 0300-8932, E-ISSN 1579-2242, Vol. 60, no 10, p. 1070-1080Article in journal (Refereed)
    Abstract [es]

    El contenido de estas Guías de Práctica Clínica de la Sociedad Europea de Cardiología (ESC) ha sido publicado para uso exclusivamente personal y educativo. No está autorizado su uso comercial. No se permite la traducción o reproducción en ningún formato de las Guías de la ESC ni de ninguna de sus partes sin un permiso escrito de la ESC. El permiso puede obtenerse enviando una solicitud por escrito a Oxford University Press, la editorial del European Heart Journal, y parte autorizada para gestionar esos permisos en representación de la ESC.

     

  • 48.
    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.
    Aktaa, Suleman
    Camm, A. John
    Costa, Francisco
    Di Biase, Luigi
    Duncker, David
    Fauchier, Laurent
    Fragakis, Nikolaos
    Frost, Lars
    Hijazi, Ziad
    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.
    Juhlin, Tord
    Merino, José L.
    Mont, Lluis
    Nielsen, Jens C.
    Oldgren, Jonas
    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.
    Polewczyk, Anna
    Potpara, Tatjana
    Sacher, Frederic
    Sommer, Philipp
    Tilz, Roland
    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 atrial fibrillation/flutter and catheter ablation: The European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart)2023In: European Heart Journal - Quality of Care and Clinical Outcomes, ISSN 2058-5225, E-ISSN 2058-1742, Vol. 9, no 6, p. 609-620Article in journal (Refereed)
    Abstract [en]

    AIMS: Standardized data definitions are essential for monitoring and assessment of care and outcomes in observational studies and randomized controlled trials (RCTs). The European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart) project of the European Society of Cardiology aimed to develop contemporary data standards for atrial fibrillation/flutter (AF/AFL) and catheter ablation.

    METHODS AND RESULTS: We used the EuroHeart methodology for development of data standards and formed a Working Group comprising 23 experts in AF/AFL and catheter ablation registries, as well as representatives from the European Heart Rhythm Association and EuroHeart. We conducted a systematic literature review of AF/AFL and catheter ablation registries and data standard documents to generate candidate variables. We used a modified Delphi method to reach consensus on a final variable set. For each variable, the Working Group developed permissible values and definitions, and agreed as to whether the variable was mandatory (Level 1) or additional (Level 2). In total, 70 Level 1 and 92 Level 2 variables were selected and reviewed by a wider Reference Group of 42 experts from 24 countries. The Level 1 variables were implemented into the EuroHeart IT platform as the basis for continuous registration of individual patient data.

    CONCLUSION: By means of a structured process and working with international stakeholders, harmonized data standards for AF/AFL and catheter ablation for AF/AFL were developed. In context of the EuroHeart project, this will facilitate country-level quality of care improvement, international observational research, registry-based RCTs and post-marketing surveillance of devices and pharmacotherapies.

    Download full text (pdf)
    fulltext
  • 49.
    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.
    Aktaa, Suleman
    Univ Leeds, Leeds Inst Cardiovasc & Metab Med, Leeds, W Yorkshire, England.;Univ Leeds, Leeds Inst Data Analyt, Leeds, W Yorkshire, England.;Leeds Teaching Hosp NHS Trust, Dept Cardiol, Leeds, W 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, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Maggioni, Aldo P.
    Italian Assoc Hosp Cardiologists Res Ctr ANMCO, Florence, Italy..
    Ludman, Peter
    Univ Birmingham, Inst Cardiovasc Sci, Birmingham, W Midlands, England..
    Erlinge, David
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    Casadei, Barbara
    Univ Oxford, NIHR Oxford Biomed Res Ctr, Div Cardiovasc Med, Oxford, England..
    Gale, Chris P.
    Univ Leeds, Leeds Inst Cardiovasc & Metab Med, Leeds, W Yorkshire, England.;Univ Leeds, Leeds Inst Data Analyt, Leeds, W Yorkshire, England.;Leeds Teaching Hosp NHS Trust, Dept Cardiol, Leeds, W Yorkshire, England..
    Data standards for acute coronary syndrome and percutaneous coronary intervention: the European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart)2022In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 43, no 24, p. 2269-2285Article in journal (Refereed)
    Abstract [en]

    Standardized data definitions are essential for monitoring and benchmarking the quality of care and patient outcomes in observational studies and randomized controlled trials. There are no contemporary pan-European data standards for the acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI). The European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart) project of the European Society of Cardiology (ESC) aimed to develop such data standards for ACS and PCI. Following a systematic review of the literature on ACS and PCI data standards and evaluation of contemporary ACS and PCI registries, we undertook a modified Delphi process involving clinical and registry experts from 11 European countries, as well as representatives from relevant ESC Associations, including the European Association of Percutaneous Cardiovascular Interventions (EAPCI) and Acute CardioVascular Care (ACVC). This resulted in final sets of 68 and 84 'mandatory' variables and several catalogues of optional variables for ACS and PCI, respectively. Data definitions were provided for these variables, which have been programmed as the basis for continuous registration of individual patient data in the online EuroHeart IT platform. By means of a structured process and the interaction with major stakeholders, internationally harmonized data standards for ACS and PCI have been developed. In the context of the EuroHeart project, this will facilitate country-level quality of care improvement, international observational research, registry-based randomized trials, and post-marketing surveillance of devices and pharmacotherapies.

    Download full text (pdf)
    fulltext
  • 50.
    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.
    Aktaa, Suleman
    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.
    Maggioni, Aldo P
    Wilkinson, Chris
    Casadei, Barbara
    Gale, Chris P
    Methodology for the development of international clinical data standards for common cardiovascular conditions: European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart)2021In: European Heart Journal - Quality of Care and Clinical Outcomes, ISSN 2058-5225, E-ISSN 2058-1742, Vol. 9, no 2, p. 161-168, article id qcab052Article in journal (Refereed)
    Abstract [en]

    AIMS: Data standards are consensual specifications for the representation of data arising from different sources. If provided with internationally harmonised variables, permissible values, and clinical definitions they have the potential to enable reliable between and within country analysis of care and outcomes. The European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart) is a European Society of Cardiology (ESC) project that allows participating countries to collect patient data to undertake quality improvement, observational studies, drug and device surveillance, and registry-based randomised controlled trials for cardiovascular conditions. This document describes the methodology for development of harmonised data standards for EuroHeart.

    METHODS AND RESULTS: We adopted a five-step process for the development of harmonised data standards. The process includes: (1) identification of clinical domains for data standard development by evaluating specific cardiovascular conditions with high prevalence and opportunities for quality improvement; (2) construction of data standard specifications by systematic review of the literature; (3) selection of variables by a domain specific Working Group using a modified Delphi method; (4) validation of data standards by a domain specific Reference Group; and (5) implementation of the developed data standards into an IT platform.

    CONCLUSION: This document describes the approach adopted by EuroHeart for the development of clinical data standards for cardiovascular disease. The methodology has been developed and is used by EuroHeart to create a suite of international data standards for cardiovascular diseases. The EuroHeart data standards may be used to systematically capture individual patient data about clinical care and for research.

    Download full text (pdf)
    fulltext
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