uu.seUppsala University Publications
Change search
Refine search result
123 1 - 50 of 114
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1. 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.

  • 2. 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 trial.2018In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, 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.

  • 3. 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.

  • 4. 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.

  • 5.
    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.

  • 6.
    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.

  • 7. Bingisser, Roland
    et al.
    Cairns, Charles B.
    Christ, Michael
    Collinson, Paul
    Hausfater, Pierre
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Mair, Johannes
    Price, Christopher
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Measurement of natriuretic peptides at the point of care in the emergency and ambulatory setting: Current status and future perspectives2013In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 166, no 4, p. 614-+Article in journal (Refereed)
    Abstract [en]

    The measurement of natriuretic peptides (NPs), B-type NP or N-terminal pro-B-type NP, can be an important tool in the diagnosis of acute heart failure in patients presenting to an Emergency Department (ED) with acute dyspnea, according to international guidelines. Studies and subsequent meta-analyses are mixed on the absolute value of routine NP assessment of ED patients. However, levels of NPs are likely to be used also to guide treatment and to assess risk of adverse outcomes in other patients at risk of developing heart failure, including those with pulmonary embolism or diabetes, or receiving chemotherapy. Natriuretic peptide levels, like other biomarkers, can now be measured at the point of care (POC). We have reviewed the current status of NP measurement together with the potential contribution of POC measurement of NPs to clinical care delivery in the emergency and other settings. Several POC systems for measuring NP levels are now available: these produce test results within 15 minutes and appear sufficiently sensitive and robust to be used routinely in diagnostic evaluations. Point-of-care systems could be used to assess NP levels in the ED and community outpatient settings to monitor the risk of acute heart failure. Furthermore, the use of protocol-driven POC testing of NP within the time frame of a patient consultation in the ED may facilitate and accelerate the throughput and disposition of at-risk patients. Appropriately designed clinical trials will be needed to confirm these potential benefits. It is also important that processes of care delivery are redesigned to take full advantage of the faster turnaround times provided by POC technology.

  • 8.
    Björklund, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stenestrand, Ulf
    Swahn, Eva
    Dellborg, Mikael
    Pehrsson, Kenneth
    Van De Werf, Frans
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Outcome of ST-elevation myocardial infarction treated with thrombolysis in the unselected population is vastly different from samples of eligible patients in a large-scale clinical trial2004In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 148, no 4, p. 566-573Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Patients in clinical trials of fibrinolytic agents have been shown to be younger, less often female, and to have lower risk characteristics and a better outcome compared with unselected patients with ST-elevation myocardial infarction. However, a direct comparison of patients treated with fibrinolytic agents and not enrolled versus those enrolled in a trial, including a large number of patients, has not been performed.

    METHODS:

    Prospective data from the Swedish Register of Cardiac Intensive Care on patients admitted with acute myocardial infarction treated with thrombolytic agents in 60 Swedish hospitals were linked to data on trial participants in the ASsessment of Safety and Efficacy of a New Thrombolytic (ASSENT)-2 trial of fibrinolytic agents. Baseline characteristics, treatments, and long-term outcome were evaluated in 729 trial participants (A2), 2048 nonparticipants at trial hospitals (non-A2), and 964 nonparticipants at other hospitals (non-A2-Hosp).

    RESULTS:

    Nontrial patients compared with A2 patients were older and had higher risk characteristics and more early complications, although the treatments were similar. Patients at highest risk of death were the least likely to be enrolled in the trial. The 1-year mortality rate was 8.8% versus 20.3% and 19.0% (P <.001 for both) among A2 compared with non-A2 and non-A2-Hosp patients, respectively. After adjustment for a number of risk factors, the 1-year mortality rate was still twice as high in nontrial compared with A2 patients.

    CONCLUSIONS:

    The adjusted 1-year mortality rate was twice as high in patients treated with fibrinolytic agents and not enrolled in a clinical trial compared with those enrolled. One major reason for the difference in outcome appeared to be the selection of less critically ill patients to the trial.

  • 9. Brilakis, Emmanouil S.
    et al.
    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.
    Meier, Bernhard
    Cools, Frank
    Claeys, Marc J.
    Cornel, Jan H.
    Aylward, Philip
    Lewis, Basil S.
    Weaver, Douglas
    Brandrup-Wognsen, Gunnar
    Stevens, Susanna R.
    Himmelmann, Anders
    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.
    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.
    Effect of ticagrelor on the outcomes of patients with prior coronary artery bypass graft surgery: Insights from the PLATelet inhibition and patient outcomes (PLATO) trial2013In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 166, no 3, p. 474-480Article in journal (Refereed)
    Abstract [en]

    Background Patients with prior coronary artery bypass graft surgery (CABG) who present with an acute coronary syndrome have a high risk for recurrent events. Whether intensive antiplatelet therapy with ticagrelor might be beneficial compared with clopidogrel is unknown. In this substudy of the PLATO trial, we studied the effects of randomized treatment dependent on history of CABG. Methods Patients participating in PLATO were classified according to whether they had undergone prior CABG. The trial's primary and secondary end points were compared using Cox proportional hazards regression. Results Of the 18,613 study patients, 1,133 (6.1%) had prior CABG. Prior-CABG patients had more high-risk characteristics at study entry and a 2-fold increase in clinical events during follow-up, but less major bleeding. The primary end point (composite of cardiovascular death, myocardial infarction, and stroke) was reduced to a similar extent by ticagrelor among patients with (19.6% vs 21.4%; adjusted hazard ratio [HR], 0.91 [0.67, 1.24]) and without (9.2% vs 11.0%; adjusted HR, 0.86 [0.77, 0.96]; P-interaction = .73) prior CABG. Major bleeding was similar with ticagrelor versus clopidogrel among patients with (8.1% vs 8.7%; adjusted HR, 0.89 [0.55, 1.47]) and without (11.8% vs 11.4%; HR, 1.08 [0.98, 1.20]; P-interaction =.46) prior CABG. Conclusions Prior-CABG patients presenting with acute coronary syndrome are a high-risk cohort for death and recurrent cardiovascular events but have a lower risk for major bleeding. Similar to the results in no-prior-CABG patients, ticagrelor was associated with a reduction in ischemic events without an increase in major bleeding.

  • 10.
    Calais, Fredrik
    et al.
    Univ Orebro, Fac Hlth, Dept Cardiol, S-70362 Orebro, Sweden..
    Lagerqvist, Bo
    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.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    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.
    Frobert, Ole
    Univ Orebro, Fac Hlth, Dept Cardiol, S-70362 Orebro, Sweden..
    Thrombus aspiration in patients with large anterior myocardial infarction: A Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia trial substudy2016In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 172, p. 129-134Article in journal (Refereed)
    Abstract [en]

    Background The TASTE trial did not demonstrate clinical benefit of thrombus aspiration (TA). High-risk patients might benefit from TA. Methods The TASTE trial was a multicenter, randomized, controlled, open-label trial obtaining end points from national registries. Patients (n = 7,244) with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) were randomly assigned 1: 1 to TA and PCI or to PCI alone. We assessed the 1-year clinical effect of TA in a subgroup with potentially large anterior STEMI: mid or proximal left anterior descending coronary artery infarct lesion, thrombolysis in myocardial infarction 0 to 2 flow, and symptom onset to PCI time = 5 hours. In this substudy, patient eligibility criteria corresponded to that of the INFUSE-AMI study. Results In total, 1,826 patients fulfilled inclusion criteria. All-cause mortality at 1 year of patients randomized to TA did not differ from those randomized to PCI only (hazard ratio [HR] 1.05, 95% CI 0.74-1.49, P = .77). Rates of rehospitalization for myocardial infarction, heart failure, and stent thrombosis did not differ between groups (HR 0.87, 95% CI 0.51-1.46, P = .59; HR 1.10 95% CI 0.77-1.58, P = .58; and HR 0.75, 95% CI 0.30-1.86, P = .53, respectively). This was also the case for the combined end point of all-cause mortality and rehospitalization for myocardial infarction, heart failure, or stent thrombosis (HR 1.00, 95% CI 0.79-1.26, P = .99). Conclusion In patients with STEMI and large area of myocardium at risk, TA did not affect outcome within 1 year.

  • 11.
    Carlhed, Rickard
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bojestig, Mats
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindström, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Peterson, Anette
    Åberg, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Improved adherence to Swedish national guidelines for acute myocardial infarction: the Quality Improvement in Coronary Care (QUICC) study2006In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 152, no 6, p. 1175-1181Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The adherence to evidence-based treatment guidelines for acute myocardial infarction (AMI) is still suboptimal. Therefore, we designed a study to evaluate the effects of a collaborative quality improvement (QI) intervention on the adherence to AMI guidelines. The intervention used a national web-based quality registry to generate local and regular real-time performance feedback. METHODS: A 12-month baseline measurement of the adherence rates was retrospectively collected, comprising the period July 1, 2001, through June 30, 2002. During the intervention period of November 1, 2002, through April 30, 2003, multidisciplinary teams from 19 nonrandomized intervention hospitals were subjected to a multifaceted QI-oriented intervention. Another 19 hospitals, unaware of their status as controls, were matched to the intervention hospitals. During the postintervention measurement period of May 1, 2003, through April 30, 2004, a total of 6726 consecutive patients were included at the intervention (n = 3786) and control (n = 2940) hospitals. The outcome measures comprised 5 Swedish national guideline-derived quality indicators, compared between baseline and postintervention levels in the control and QUICC intervention hospitals. RESULTS: In the control and QI intervention hospitals, the mean absolute increase of patients receiving angiotensin-converting enzyme inhibitors was 1.4% vs 12.6% (P = .002), lipid-lowering therapy 2.3% vs 7.2% (P = .065), clopidogrel 26.3% vs 41.2% (P = .010), heparin/low-molecular weight heparin 5.3% vs 16.3% (P = .010), and coronary angiography 6.2% vs 16.8% (P = .027), respectively. The number of QI intervention hospitals reaching a treatment level of at least 70% in 4 or 5 of the 5 indicators was 15 and 5, respectively. In the control group, no hospital reached 70% or more in just 4 of the 5 indicators. CONCLUSIONS: By combining a systematic and multidisciplinary QI collaborative with a web-based national quality registry with functionality allowing real-time performance feedback, major improvements in the adherence to national AMI guidelines can be achieved.

  • 12. Cornel, Jan H.
    et al.
    Becker, Richard C.
    Goodman, Shaun G.
    Husted, Steen
    Katus, Hugo
    Santoso, Anwar
    Steg, Gabriel
    Storey, Robert F.
    Vintila, Marius
    Sun, Jie L.
    Horrow, Jay
    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.
    Harrington, Robert
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Prior smoking status, clinical outcomes, and the comparison of ticagrelor with clopidogrel in acute coronary syndromes-Insights from the PLATelet inhibition and patient Outcomes (PLATO) trial2012In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 164, no 3, p. 334-342Article in journal (Refereed)
    Abstract [en]

    Background Habitual smoking has been associated with increased platelet reactivity, increased risk of thrombotic complications and greater efficacy of clopidogrel therapy over placebo. In the PLATO trial, ticagrelor compared to clopidogrel in patients with acute coronary syndromes (ACS) reduced the primary composite end point of vascular death, myocardial infarction and stroke, without increasing overall rates of major bleeding. We evaluated the results in relation to smoking habits.

    Methods Interactions between habitual smokers (n = 6678) and in ex/nonsmokers (n = 11,932) and the effects of randomized treatments on ischemic and bleeding outcomes were evaluated by Cox regression analyses.

    Results Habitual smokers had an overall lower risk profile and more often ST-elevation ACS. After adjustment for baseline imbalances, habitual smoking was associated with a higher incidence of definite stent thrombosis (adjusted HR, 1.44 [95% CI, 1.07-1.94]); there were no significant associations with other ischemic or bleeding end points. The effects of ticagrelor compared to clopidogrel were consistent for all outcomes regardless of smoking status. Thus, there was a similar reduction in the primary composite end point for habitual smokers (adjusted HR, 0.83 [95% CI, 0.68-1.00]) and ex/nonsmokers (adjusted HR, 0.89 [95% CI, 0.79-1.00]) (interaction P = .50), and in definite stent thrombosis for habitual smokers (adjusted HR, 0.59 [0.39-0.91]) and ex/nonsmokers (adjusted HR, 0.69 [95% CI, 0.45-1.07]) (interaction P = .61).

    Conclusions In patients hospitalized with ACS, habitual smoking is associated with a greater risk of subsequent stent thrombosis. The reduction of vascular death, myocardial infarction, stroke, and stent thrombosis by ticagrelor compared to clopidogrel is consistent regardless of smoking habits.

  • 13. Cornel, Jan 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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Stevens, Susanna R.
    Neely, Megan L.
    Liaw, Danny
    Miller, Julie
    Mohan, Puneet
    Amerena, John
    Raev, Dimitar
    Huo, Yong
    Urina-Triana, Miguel
    Cazorla, Alex Gallegos
    Vinereanu, Dragos
    Fridrich, Viliam
    Harrington, Robert A.
    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.
    Alexander, John H.
    Anticoagulant therapy and outcomes in patients with prior or acute heart failure and acute coronary syndromes: Insights from the APixaban for PRevention of Acute ISchemic Events 2 trial2015In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 169, no 4, p. 531-538Article in journal (Refereed)
    Abstract [en]

    Background Clinical outcomes and the effects of oral anticoagulants among patients with acute coronary syndrome (ACS) and either a history of or acute heart failure (HF) are largely unknown. We aimed to assess the relationship between prior HF or acute HF complicating an index ACS event and subsequent clinical outcomes and the efficacy and safety of apixaban compared with placebo in these populations. Methods High-risk patients were randomly assigned post-ACS to apixaban 5.0 mg or placebo twice daily. Median follow-up was 8 (4-12) months. The primary outcome was cardiovascular death, myocardial infarction, or stroke. The main safety outcome was thrombolysis in myocardial infarction major bleeding. Results Heart failure was reported in 2,995 patients (41%), either as prior HF (2,076 [28%]) or acute HF (2,028 [27%]). Patients with HF had a very high baseline risk and were more often managed medically. Heart failure was associated with a higher rate of the primary outcome (prior HF: adjusted hazard ratio [HR] 1.73, 95% CI 1.42-2.10, P < .0001, acute HF: adjusted HR 1.65, 95% CI 1.35-2.01, P < .0001) and cardiovascular death (prior HF: HR 2.54, 95% CI 1.82-3.54, acute HF: adjusted HR 2.52, 95% CI 1.82-3.50). Patients with acute HF also had significantly higher rates of thrombolysis in myocardial infarction major bleeding (prior HF: adjusted HR 1.22, 95% CI 0.65-2.27, P = .54, acute HF: adjusted HR 1.78, 95% CI 1.03-3.08, P = .04). There was no statistical evidence of a differential effect of apixaban on clinical events or bleeding in patients with or without prior HF; however, among patients with acute HF, there were numerically fewer events with apixaban than placebo (14.8 vs 19.3, HR 0.76, 95% CI 0.57-1.01, interaction P = .13), a trend that was not seen in patients with prior HF or no HF. Conclusions In high-risk patients post-ACS, both prior and acute HFs are associated with an increased risk of subsequent clinical events. Apixaban did not significantly reduce clinical events and increased bleeding in patients with and without HF; however, there was a tendency toward fewer clinical events with apixaban in patients with acute HF.

  • 14.
    De Caterina, Raffaele
    et al.
    Univ G DAnnunzio, Inst Cardiol, Chieti, Italy.;Univ G DAnnunzio, Ctr Excellence Aging, Chieti, Italy..
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alexander, John H.
    Duke Med, Duke Clin Res Inst, Durham, NC USA..
    Al-Khatib, Sana M.
    Duke Med, Duke Clin Res Inst, Durham, NC USA..
    Bahit, M. Cecilia
    INECO Neurociencias Orono, Rosario, Santa Fe, Argentina..
    Goto, Shinya
    Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan..
    Hanna, Michael
    Bristol Myers Squibb Co, Princeton, NJ 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, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    Hohnloser, Stefan
    Goethe Univ Frankfurt, Frankfurt, Germany..
    Hylek, Elaine M.
    Boston Univ, Med Ctr, Boston, MA 02215 USA..
    Lanas, Fernando
    Univ La Frontera, Temuco, Chile..
    Lopes, Renato D.
    Duke Med, Duke Clin Res Inst, Durham, NC USA..
    Lopez-Sendon, Jose
    Hosp Univ La Paz, IdiPaz Madrid, Madrid, Spain..
    Renda, Giulia
    Univ G DAnnunzio, Inst Cardiol, Chieti, Italy.;Univ G DAnnunzio, Ctr Excellence Aging, Chieti, Italy..
    Horowitz, John
    Queen Elizabeth Hosp, Adelaide, SA, Australia..
    Granger, Christopher B.
    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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    History of bleeding and outcomes with apixaban versus warfarin in patients with atrial fibrillation in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial2016In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 175, p. 175-183Article in journal (Refereed)
    Abstract [en]

    Aims History of bleeding strongly influences decisions for anticoagulation in atrial fibrillation (AF). We analyzed outcomes in relation to history of bleeding and randomization in ARISTOTLE trial patients. Methods and results The on-treatment safety population included 18,140 patients receiving at least 1 dose of study drug (apixaban) or warfarin. Centrally adjudicated outcomes in relation to bleeding history were analyzed using a Cox proportional hazards model adjusted for randomized treatment and established risk factors. Efficacy end points were analyzed on the randomized (intention to treat) population. A bleeding history was reported at baseline in 3,033 patients (16.7%), who more often were male, with a history of prior stroke/transient ischemic attack/systemic embolism and diabetes; higher CHADS2 scores, age, and body weight; and lower creatinine clearance and mean systolic blood pressure. Major (but not intracranial) bleeding occurred more frequently in patients with versus without a history of bleeding (adjusted hazard ratio 1.35, 95% CI 1.14-1.61). There were no significant interactions between bleeding history and treatment for stroke/systemic embolism, hemorrhagic stroke, death, or major bleeding, with fewer outcomes with apixaban versus warfarin for all of these outcomes independent of the presence/absence of a bleeding history. Conclusion In patients with AF in a randomized clinical trial of oral anticoagulants, a history of bleeding is associated with several risk factors for stroke and portends a higher risk of major-but not intracranial-bleeding, during anticoagulation. However, the beneficial effects of apixaban over warfarin for stroke, hemorrhagic stroke, death, or major bleeding remains consistent regardless of history of bleeding.

  • 15. Diderholm, Erik
    et al.
    Andrén, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Frostfeldt, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Genberg, Margareta
    Jernberg, Tomas
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Venge, Per
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    The prognostic and therapeutic implications of increased troponin T levels and ST depression in unstable coronary artery disease: the FRISC II invasive troponin T electrocardiogram substudy2002In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 143, no 5, p. 760-767Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In unstable coronary artery disease, both increased troponin T level and occurrence of ST-segment depression are associated with a worse prognosis. In the Fast Revascularisation in InStability in Coronary disease trial II invasive study, we evaluated whether the troponin T level, alone and combined with ST depression, identified more severe coronary artery disease or a greater efficacy of an early invasive strategy.

    METHODS: In the study, 2457 patients with unstable coronary artery disease were randomized to early invasive or noninvasive strategy. Troponin T value and admission electrocardiogram results were available in 2286 patients.

    RESULTS: In the noninvasive cohort, death or myocardial infarction occurred in 16.6% with troponin T level > or =0.03 microg/L versus 8.5% with troponin T level < 0.03 microg/L (P <.001). In the invasive group, 49% of patients with both ST depression and troponin T level > or =0.03 microg/L had 3-vessel or left main disease compared with 17% if neither finding was present (P <.001). The invasive strategy reduced death/myocardial infarction at 12 months in the cohort with both ST depression and troponin T level > or =0.03 microg/L from 22.1% to 13.2% (risk ratio, 0.60; 95% confidence interval, 0.43 to 0.82; P =.001). In the cohort with either ST depression or troponin T level > or =0.03 microg/L or neither of these findings, the absolute gain of the invasive strategy was smaller and more uncertain.

    CONCLUSION: Patients with unstable coronary artery disease with the combination of troponin T level > or =0.03 microg/L and ST depression have a poor prognosis and, in half of the cases, 3-vessel or left main disease. In these patients, an early invasive strategy will substantially reduce death/myocardial infarction.

  • 16.
    Ducrocq, Gregory
    et al.
    FACT, Paris, France.;Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, Paris, France.;Univ Paris Diderot, Sorbonne Paris Cite, Paris, France.;INSERM, Unite 1148, Paris, France..
    Schulte, Phillip J.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.;Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA..
    Budaj, Andrzej
    Grochowski Hosp, Postgrad Med Sch, Warsaw, Poland..
    Cornel, Jan H.
    Noordwest Ziekenhuisgrp, Dept Cardiol, Alkmaar, Netherlands..
    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.
    Himmelmann, Anders
    AstraZeneca Res & Dev, Gothenburg, Sweden..
    Hunted, Steen
    Hosp Unit Wwst, Med Dept, Herning Holstebro, Denmark..
    Storey, Robert F.
    Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England..
    Cannon, Christopher P.
    Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.;Baim Inst Clin Res Boston, Boston, MA USA..
    Becker, Richard C.
    Univ Cincinnati, Coll Med, Heart Lung & Vasc Inst, Div Cardiovasc Hlth & Dis, Cincinnati, OH USA..
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Katus, Hugo A.
    Univ Klinikum Heidelberg, Med Klin, Heidelberg, Germany..
    Lopes, Renato D.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA..
    Sorbets, Enunanuel
    FACT, Paris, France.;Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, Paris, France.;INSERM, Unite 1148, Paris, France.;Hop Avicenne, AP HP, Bobigny, France.;Univ Paris 13, Bobigny, France..
    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.
    Steg, Philippe Gabriel
    FACT, Paris, France.;Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, Paris, France.;Univ Paris Diderot, Sorbonne Paris Cite, Paris, France.;INSERM, Unite 1148, Paris, France.;NHLI Imperial Coll, Royal Brampton Hosp, ICMS, London, England..
    Balancing the risk of spontaneous ischemic and major bleeding events in acute coronary syndromes2017In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 186, p. 91-99Article in journal (Refereed)
    Abstract [en]

    Background: Evaluation of antithrombotic treatments for acute coronary syndromes (ACS) requires balancing ischemic and bleeding risks to assess net benefit. We sought to compare the relative effects of ischemic and bleeding events on mortality.

    Methods: In the PLATelet inhibition and patient Outcomes (PLATO) trial, we compared spontaneous ischemic events (myocardial infarction or stroke) with spontaneous major bleeding events (PLATO major, Thrombolysis In Myocardial Infarction [TIMI] major, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries [GUSTO] severe) with respect to risk of mortality using time-dependent Cox proportional hazards models. The comparison was performed using ratio of hazard ratios for mortality increase after ischemic vs bleeding events.

    Results: A total of 822 patients (4.4%) had >= 1 spontaneous ischemic event; 485 patients (2.6%), >= 1 spontaneous PLATO major bleed, 282 (1.5%), >= 1 spontaneous TIMI major bleed; and 207 (1.1%), >= 1 spontaneous severe GUSTO bleed. In patients who had both events, bleeding occurred first in most patients. Regardless of classification, major bleeding events were associated with increased short- and long-term mortality that were not significantly different from the increase associated with spontaneous ischemic events: ratio of hazard ratios (95% Cls) for short- and long-term mortality after spontaneous ischemic vs bleeding events: 1.46 (0.98-2.19) and 0.92 (0.52-1.62) (PLATO major); 1.26 (0.80-1.96) and 1.19 (0.58-2.24) (TIMI major), 0.72 (0.47-1.10) and 0.83 (0.38-1.79) (GUSTO severe) (all P > 0.05)

    Conclusions: In patients with ACS on dual antiplatelet therapy, spontaneous major bleeding events seem "prognostically equivalent" to spontaneous ischemic complications. This result allows quantitative comparisons between both actual and predicted bleeding and ischemic risks. Our findings help to better define net clinical benefit of antithrombotic treatments and more accurately estimate mortality after ischemic and bleeding events in patients with ACS.

  • 17.
    Dunder, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lithell, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Evaluation of a scoring scheme, including proinsulin and the apolipoprotein B/apolipoprotein A1 ratio, for the risk of acute coronary events in middle-aged men: Uppsala Longitudinal Study of Adult Men (ULSAM)2004In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 148, no 4, p. 596-601Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In recent years, the importance of circulating levels of proinsulin and apolipoproteins as risk factors for myocardial infarction (MI) has been highlighted. The aims of the current study were to investigate whether introduction of these new markers of coronary risk could improve the performance of a risk prediction score and to compare this new score with traditional scoring schemes, such as the Framingham Study and the Prospective Cardiovascular Munster (PROCAM) Study schemes.

    METHODS: From 1970 to 1973 all 50-year-old men in Uppsala, Sweden, were invited to participate in a health survey aimed at identifying risk factors for cardiovascular disease (the Uppsala Longitudinal Study of Adult Men [ULSAM] cohort). The current study investigated metabolic characteristics at baseline and the incidence of fatal and nonfatal MI (n = 251) during 28.7 years of follow-up in 1108 men who were free of coronary heart disease at baseline.

    RESULTS: The risk prediction score was derived from one half of the population sample from the ULSAM cohort and included systolic blood pressure, smoking, family history of MI, serum proinsulin, and the ratio between apolipoprotein B and apolipoprotein A1. The score was highly predictive for future MI (hazard ratio, 1.77 for a 1 SD increase; 95% CI, 1.49 to 2.10, P <.0001) in the other half of the population that was not used for generating the score. The ULSAM score performed slightly better than the Framingham and PROCAM scores (evaluated as areas under the receiver operating curves; Framingham, 61%; PROCAM, 63%; ULSAM, 66%; P =.08).

    CONCLUSIONS: A risk prediction score for MI including proinsulin and the ratio between apolipoprotein B and apolipoprotein A1 was developed in middle-aged men. This score was highly predictive for future fatal and nonfatal MI and proved to be at least as good as the Framingham and the PROCAM scores, being based on traditional risk factors.

  • 18.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Al-Shakarchi, Jinan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    High-sensitive cardiac troponin T and its relations to cardiovascular risk factors, morbidity, and mortality in elderly men2013In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 166, no 3, p. 541-+Article in journal (Refereed)
    Abstract [en]

    Background Cardiac troponin is emerging as risk indicator in community-dwelling populations. In this study, we investigated the associations of cardiac troponin T (cTnT) to cardiovascular (CV) disease and outcome in elderly men. Methods Cardiac troponin T was measured using a high-sensitive assay in 940 men aged 71 years participating in the Uppsala Longitudinal Study of Adult Men. We assessed both the cross-sectional associations of cTnT to CV risk factors and morbidities including cancer and the longitudinal associations to outcomes over 10 years of follow-up. Results Cardiac troponin T levels were measurable in 872 subjects (92.8%). In the cross-sectional analyses, cTnT was associated to CV risk factors (diabetes, smoking, and obesity), renal dysfunction, CV disease including atrial fibrillation and coronary artery disease, and biomarkers of inflammation and left ventricular dysfunction. In the longitudinal analyses, cTnT independently predicted total mortality and CV events including stroke. The standardized adjusted hazard ratio regarding the composite CV end point was 1.5 (95% CI 1.3-1.8), P < .001, for men with prevalent CV disease and 1.2 (95% CI 1.0-1.4), P = .02, for men without. Cardiac troponin T improved discrimination metrics for all outcomes in the total population. This was mainly driven by the prognostic value of cTnT in subjects with prevalent CV disease. Conclusions In community-dwelling men, cTnT levels are associated to CV risk factors and morbidities and predict both fatal and nonfatal CV events. The relations to outcome are mainly seen in men with prevalent CV disease indicating that the prognostic value of cTnT in subjects free from CV disease is limited.

  • 19.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Armstrong, Paul W.
    Califf, Robert M.
    Simoons, Maarten L.
    Venge, Per
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    ST2 and mortality in non-ST-segment elevation acute coronary syndrome2010In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 159, no 5, p. 788-794Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: ST2 is a member of the interleukin-1 receptor family that is up-regulated in conditions associated with increased myocardial strain. ST2 has been shown to be independently predictive of adverse outcome in heart failure and ST-segment elevation myocardial infarction, but its prognostic value in non-ST-elevation acute coronary syndrome (NSTE-ACS) has not been established. METHODS: We measured ST2 at randomization and after 24, 48, and 72 hours in 403 NSTE-ACS patients from the GUSTO IV study, and studied its kinetics and its associations to clinical baseline factors and 1-year mortality. RESULTS: Median ST2 levels decreased from 28.4 U/mL at randomization to 21.8 U/mL at 72 hours (P < .001). Peak levels were noted 6 to 17 hours after symptom onset. Randomization ST2 levels were independently associated to N-terminal pro-B-type natriuretic peptide but otherwise exhibited only weak relations to cardiovascular risk factors and comorbidities, and biomarkers of myocardial necrosis or inflammation. ST2 was related to 1-year mortality independently of clinical risk indicators (odds ratio 2.3 [95% CI 1.1-4.6], P = .03) but lost its predictive value after additional adjustment for prognostic biomarkers, in particular N-terminal pro-B-type natriuretic peptide. CONCLUSIONS: ST2 levels are elevated early in NSTE-ACS and predict 1-year mortality. Our data indicate that ST2 represents an interesting novel pathophysiologic pathway in the setting of ischemia-related myocardial dysfunction. However, future prospective evaluations in larger populations are needed before the clinical utility of ST2 can be determined.

  • 20.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jernberg, T.
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    High-sensitivity cardiac troponin T, left ventricular function, and outcome in non-ST elevation acute coronary syndrome2018In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 197, p. 70-76Article in journal (Refereed)
    Abstract [en]

    Background Cardiac troponin (cTn) levels reflect infarct size and depressed left ventricular ejection fraction (LVEF) in patients with non-ST elevation acute coronary syndrome (NSTE-ACS). However, there is very limited information on whether cTn measured with a high-sensitivity (hs) assay would provide incremental prognostic information to the LVEF in NSTE-ACS patients. Methods This was a registry-based study (SWEDEHEART registry) investigating 20,652 NSTE-ACS patients with available information on hs-cTnT (highest level recorded during the hospitalization) and the LVEF estimated using echocardiography. All patients had been followed for 1 year. Results Hs-cTnT levels independently predicted major cardiovascular events (MACE) in cohorts with normal, slightly depressed, moderately depressed, and severely depressed LVEF. The adjusted hazard ratios in these cohorts were 1.18 (95% CI 1.13-1.23), 1.12 (95% CI 1.06-1.18), 1.12 (95% CI 1.06-1.19), and 1.21 (95% CI 1.13-1.30), respectively. Hs-cTnT levels were particularly predictive for cardiovascular mortality and readmission for heart failure. Excluding patients with previous cardiac disease did not affect the overall interrelations of hs-cTnT and LVEF with MACE. Conclusions Hs-cTnT levels provide incremental prognostic value independent of the LVEF in patients with NSTE-ACS. Hs-cTnT is particularly predictive for MACE in patients with severely depressed LVEF but also in those with a normal LVEF. Accordingly, a normal LVEF should not be used as an argument not to target patients to thorough workup.

  • 21.
    Eggers, Kai M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Cardiac troponin I levels in patients with non-ST-elevation acute coronary syndrome: the importance of gender2014In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 168, no 3, p. 317-324.e1Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Measurement of high-sensitivity cardiac troponin levels is increasingly used in non-ST-elevation acute coronary syndrome (NSTE-ACS). However, studies investigating the distribution and prognostic implications of high-sensitivity troponin levels in men and women separately are currently lacking.

    METHODS: Cardiac troponin I (cTnI) levels were determined using a high-sensitivity assay (Abbott Laboratories, Abbott Park, IL) in 1,677 male and 1,073 female NSTE-ACS patients participating in the GUSTO IV study. The prognostic associations of cTnI to outcome (30-day composite end point of recurrent myocardial infarction and 1-year mortality) were assessed in multivariable models, using cTnI both as a continuous variable and dichotomized at different sets of single and gender-specific 99th percentiles.

    RESULTS: Median cTnI levels were 947 and 175 ng/L in men and women, respectively (P < .001). The adjusted odds ratios for cTnI (ln) were similar in men and women. The adjusted odds ratios for cTnI above the tested 99th percentiles levels in contrast were twice as high in women compared with men. This was a consequence of differences in the cTnI distribution and risk gradients across cTnI levels, in particular due to lower event rates in women without cTnI elevation. Gender-specific cutoffs did not improve risk prediction.

    CONCLUSIONS: Despite overall lower levels, cTnI above the tested 99th percentiles exhibited stronger prognostic information in women with NSTE-ACS compared with men. This likely reflects differences in the pathophysiology and the clinical presentation in NSTE-ACS. Our data, thus, emphasize that women with symptoms of unstable coronary artery disease encompass a broader risk panorama than men.

  • 22.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Kempf, Tibor
    Venge, Per
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wollert, Kai C.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Improving long-term risk prediction in patients with acute chest pain: The Global Registry of Acute Coronary Events (GRACE) risk score is enhanced by selected nonnecrosis biomarkers2010In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 160, no 1, p. 88-94Article in journal (Refereed)
    Abstract [en]

    Background The Global Registry of Acute Coronary Events (GRACE) risk score is widely recommended for risk assessment in patients with acute coronary syndrome. However, there is limited knowledge regarding the utility of this score for long-term risk prediction in unselected patients with acute chest pain and whether it might be improved by the integration of nonnecrosis biomarkers. Methods We calculated the GRACE risk score in 453 chest pain patients and assessed its value for risk assessment together with the additive prognostic information obtained from N-terminal pro-B-type natriuretic peptide, C-reactive protein, growth differentiation factor-15 (GDF-15), and cystatin C. Results After a median follow-up of 5.8 years, 92 patients (20.7%) had died. The GRACE risk score was significantly higher in patients who died (median 146 vs 93, P < .001) and provided a c-statistic regarding mortality of 0.78. A significant increase of the c-statistic was achieved only after addition of GDF-15 (c-statistic 0.81, P = .003) and, to a minor extent, after addition of cystatin C (c-statistic 0.81, P = .035). Assessment of the integrated discriminative improvement yielded similar results. N-terminal pro-B-type natriuretic peptide had only limited incremental prognostic value, and C-reactive protein was not predictive for outcome. Conclusion The GRACE risk score allows for the prediction of mortality in chest pain patients even after almost 6 years of follow-up. However, its predictive value could be further enhanced by the addition of selected nonnecrosis biomarkers, in particular GDF-15 or cystatin C. (Am Heart J 2010; 160: 88-94.)

  • 23.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Venge, Per
    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.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Pathophysiologic mechanisms of persistent cardiac troponin I elevation in stabilized patients after an episode of acute coronary syndrome2008In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 156, no 3, p. 588-594Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Recently, a high prevalence of small persistent cardiac troponin I (cTnI) elevations has been reported in patients who had been stabilized after a recent episode of acute coronary syndrome (ACS). We now have studied the associations of persistently elevated cTnI levels to cardiac performance, inflammation, coagulation, coronary status, and treatment strategy in these patients. METHODS AND RESULTS: Cardiac troponin I was determined at 6 weeks, 3 months, and 6 months after randomization in 898 stabilized ACS patients from the FRagmin and Fast Revascularization during InStability in Coronary artery disease (FRISC) II trial and using the high-sensitive Access AccuTnI assay (Beckman Coulter, Fullerton, CA). All patients were followed up for at least 5 years. Persistent cTnI elevation >0.01 microg/L at the 3 measurement instances was detected in 233 patients (26%). N-terminal pro-brain natriuretic peptide (NT-proBNP) at 6 months (OR 2.5, 95% CI 2.0-3.1), male sex (OR 2.2, 95% CI 1.4-3.7), and randomization to an early invasive strategy (OR 1.8, 95% CI 1.2-2.7) independently predicted persistently elevated cTnI levels. Persistently cTnI-positive patients in the invasive cohort had significantly lower NT-proBNP levels compared to noninvasively treated patients, indicating that the mechanisms causing cTnI elevation in this group may be prognostically less harmful. No independent associations were found for markers of inflammation or coagulation. CONCLUSION: Persistent cTnI elevation occurs frequently late after an ACS. The NT-proBNP level at 6 months was the strongest predictor for elevated cTnI levels that thus appear to be predominantly related to impaired left ventricular function.

  • 24.
    Eggers, Kai
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nordenskjöld, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Diagnostic value of serial measurement of cardiac markers in patients with chest pain: limited value of adding myoglobin to troponin I for exclusion of myocardial infarction2004In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 148, no 4, p. 574-581Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Despite improved laboratory assays for cardiac markers and a revised standard for definition of myocardial infarction (AMI), early detection of coronary ischemia in unselected patients with chest pain remains a difficult challenge.

    METHODS:

    Rapid measurements of troponin I (TnI), creatine kinase MB (CK-MB), and myoglobin were performed in 197 consecutive patients with chest pain and a nondiagnostic electrocardiogram for AMI. The early diagnostic performances of these markers and different multimarker strategies were evaluated and compared. Diagnosis of AMI was based on European Society of Cardiology/American College of Cardiology criteria.

    RESULTS:

    At a given specificity of 95%, TnI yielded the highest sensitivity of all markers at all time points. A TnI cutoff corresponding to the 10% coefficient of variation (0.1 microg/L) demonstrated a cumulative sensitivity of 93% with a corresponding specificity of 81% at 2 hours. The sensitivity was considerably higher compared to CK-MB and myoglobin, even considering patients with a short delay until admission. Using the 99th percentile of TnI results as a cutoff (0.07 microg/L) produced a cumulative sensitivity of 98% at 2 hours, but its usefulness was limited due to low specificities. Multimarker strategies including TnI and/or myoglobin did not provide a superior overall diagnostic performance compared to TnI using the 0.1 microg/L cutoff.

    CONCLUSION:

    A TnI cutoff corresponding to the 10% coefficient of variation was most appropriate for early diagnosis of AMI. A lower TnI cutoff may be useful for very early exclusion of AMI. CK-MB and in particular myoglobin did not offer additional diagnostic value.

  • 25.
    Elfwen, Ludvig
    et al.
    Karolinska Inst, Soder Sjukhuset, Dept Clin Sci & Educ, Solna, Sweden.
    Lagedal, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    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.
    Jonsson, Martin
    Karolinska Inst, Ctr Resuscitat Sci, Dept Med, Solna, Sweden.
    Jensen, Ulf
    Karolinska Inst, Soder Sjukhuset, Dept Clin Sci & Educ, Solna, Sweden.
    Ringh, Mattias
    Karolinska Inst, Ctr Resuscitat Sci, Dept Med, Solna, Sweden.
    Claesson, Andreas
    Karolinska Inst, Ctr Resuscitat Sci, Dept Med, Solna, Sweden.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Herlitz, Johan
    Univ Boras, Ctr Prehosp Res Western Sweden, Boras, Sweden;Univ Boras, Sch Hlth Sci, Boras, Sweden;Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nordberg, Per
    Karolinska Inst, Ctr Resuscitat Sci, Dept Med, Solna, Sweden.
    Coronary angiography in out-of-hospital cardiac arrest without ST elevation on ECG-Short- and long-term survival2018In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 200, p. 90-95Article in journal (Refereed)
    Abstract [en]

    Background: The potential benefit of early coronary angiography in out-of-hospital cardiac arrest (OHCA) patients without ST elevation on ECG is unclear. The aim of this study was to evaluate the association between early coronary angiography and survival in these patients.

    Methods: Nationwide observational study between 2008 and 2013. Included were patients admitted to hospital after witnessed OHCA, with shockable rhythm, age 18 to 80 years and unconscious. Patients with ST-elevation on ECG were excluded. Patients that underwent early CAG (within 24 hours) were compared with no early CAG (later during the hospital stay or not at all). Outcomes were survival at 30 days, 1 year, and 3 years. Multivariate analysis included pre-hospital factors, comorbidity and ECG-findings.

    Results: In total, 799 OHCA patients fulfilled the inclusion criteria, of which 275 (34%) received early CAG versus 524 (66%) with no early CAG. In the early CAG group, the proportion of patients with an occluded coronary artery was 27% and 70% had at least one significant coronary stenosis (defined as narrowing of coronary lumen diameter of >= 50%). The 30-day survival rate was 65% in early CAG group versus 52% with no early CAG (P < .001). The adjusted OR was 1.42 (95% CI 1.00-2.02). The one-year survival rate was 62% in the early CAG group versus 48% in the no early CAG group with the adjusted hazard ratio of 1.35 (95% CI 1.04-1.77).

    Conclusion: In this population of bystander-witnessed cases of out-of-hospital cardiac arrest with shockable rhythm and ECG without ST elevation, early coronary angiography may be associated with improved short and long term survival.

  • 26.
    Erlinge, David
    et al.
    Lund Univ, Dept Cardiol, Clin Sci, Lund, Sweden..
    Koul, Sasha
    Lund Univ, Dept Cardiol, Clin Sci, Lund, Sweden..
    Eriksson, Peter
    Umea Univ, Dept Cardiol, Umea, Sweden..
    Schersten, Fredrik
    Lund Univ, Dept Cardiol, Clin Sci, Lund, Sweden..
    Omerovic, Elmir
    Sahlgrenska Univ, Dept Cardiol, Gothenburg, Sweden..
    Linder, Rikard
    Karolinska Univ, Dept Cardiol, Stockholm, Sweden..
    Ostlund, Olof Petter
    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.
    Frobert, Ole
    Univ Orebro, Dept Cardiol, Fac Hlth, SE-70182 Orebro, Sweden..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bivalirudin versus heparin in non-ST and ST-segment elevation myocardial infarction-a registry-based randomized clinical trial in the SWEDEHEART registry (the VALIDATE-SWEDEHEART trial)2016In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 175, p. 36-46Article in journal (Refereed)
    Abstract [en]

    Background The optimal anticoagulant for patients with acute coronary syndrome treated with percutaneous coronary intervention (PCI) has not been validated in current practice of radial approach and pretreatment with potent P2Y12 inhibitors. Several studies have indicated increased bleeding rate and, in some instances, even increased mortality by the routine use of heparin and glycoprotein IIb/IIIa inhibitors compared to bivalirudin. Direct comparison of bivalirudin versus heparin alone has yielded contradictory results depending on study designs. Methods/design The VALIDATE-SWEDEHEART trial is a multicenter, prospective, randomized, registry-based, controlled, and open-label clinical trial in patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI undergoing PCI pretreated with ticagrelor, prasugrel, or cangrelor. We hypothesize that bivalirudin is superior to heparin alone in reducing death, myocardial infarction, and major bleeding events at 180 days (primary end point). The trial will enroll 3,000 patients with STEMI and 3,000 patients with non-STEMI undergoing PCI. The trial will use a hybrid registry-based randomized clinical trial design where inclusion, randomization, and baseline data collection are performed using The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registry. The primary composite end point (death, myocardial infarction, or major bleeding events at 180 days) will be identified through active screening after 7 and 180 days and adjudicated by a blinded central end point committee. Secondary end points and long-term outcomes will be recorded from national registries. Conclusion The VALIDATE-SWEDEHEART trial is founded on a nationwide clinical registry and uses a hybrid registry-based randomized clinical trial (RRCT) design methodology to evaluate efficacy and safety of bivalirudin as compared to heparin alone for acute coronary syndrome, in a large population receiving contemporary recommended therapies including predominantly radial invasive approach and pretreatment with potent P2Y12 inhibitors.

  • 27. Ezekowitz, Michael D.
    et al.
    Connolly, Stuart
    Parekh, Amit
    Reilly, Paul A.
    Varrone, Jeanne
    Wang, Susan
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Themeles, Ellison
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Yusuf, Salim
    Rationale and design of RE-LY: randomized evaluation of long-term anticoagulant therapy, warfarin, compared with dabigatran2009In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 157, no 5, p. 805-810Article in journal (Refereed)
    Abstract [en]

    Vitamin K antagonists (VKAs) are effective for stroke prevention in patients with atrial fibrillation (AF) but are difficult to use. Dabigatran etexilate is a prodrug that is rapidly converted to the active direct thrombin inhibitor dabigatran. It is administered in a fixed dose without laboratory monitoring and is being compared with warfarin (international normalized ratio 2-3) in the RE-LY trial. Two doses of dabigatran (110 and 150 mg BID) are being evaluated. RE-LY is a phase 3, prospective, randomized, open-label multinational (44 countries) trial of patients with nonvalvular AF and at least 1 risk factor for stroke. Recruitment concluded with a total of 18,113 patients. Patients who were VKA-naive and experienced are included in balanced proportions. The primary outcome is stroke (including hemorrhagic) or systemic embolism. Safety outcomes are bleeding, liver function abnormalities, and other adverse events. Adjudication of end points is blinded to drug assignment. The trial is expected to accrue a minimum of 450 events with a minimum 1-year of follow-up. RE-LY is the largest AF stroke prevention trial yet undertaken. It is unique because it includes equal numbers of VKA-experienced and naive patients and evaluates 2 different dosages of dabigatran, which may allow tailoring of dosing to individual patient needs. The worldwide site distribution and broad range of stroke risk further increase the general applicability of the trial. Results are expected in 2009.

  • 28.
    Ezekowitz, Michael D.
    et al.
    Thomas Jefferson Univ, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA.;Lankenau Med Ctr, Wynnewood, PA USA..
    Pollack, Charles V.
    Thomas Jefferson Univ, Philadelphia, PA 19107 USA..
    Sanders, Paul
    Pfizer, London, England..
    Halperin, Jonathan L.
    Icahn Sch Med Mt Sinai, New York, NY 10029 USA..
    Spahr, Judith
    Lankenau Inst Med Res, Wynnewood, PA USA..
    Cater, Nilo
    Pfizer, New York, NY USA..
    Petkun, William
    Bristol Myers Squibb Inc, Princeton, NJ USA..
    Breazna, Andrei
    Pfizer, New York, NY USA..
    Kirchhof, Paulus
    Univ Birmingham, SWBH UHB NHS Trusts, Inst Cardiovasc Sci, Birmingham, W Midlands, England.;Univ Hosp Munster, Dept Cardiol & Angiol, Munster, Germany..
    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.
    Apixaban compared with parenteral heparin and/or vitamin K antagonist in patients with nonvalvular atrial fibrillation undergoing cardioversion: Rationale and design of the EMANATE trial2016In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 179, p. 59-68Article in journal (Refereed)
    Abstract [en]

    Background: Stroke prevention in anticoagulation-nafve patients with atrial fibrillation undergoing cardioversion has not been systematically studied.

    Objective: To determine outcomes in anticoagulation-naive patients (defined as those receiving an anticoagulant for <48 hours during the index episode of atrial fibrillation) scheduled for cardioversion.

    Methods: This is a randomized, prospective, open-label, real-world study comparing apixaban to heparin plus warfarin. Early image-guided cardioversion is encouraged. For apixaban, the usual dose is 5 mg BID with a dose reduction to 2.5 mg BID if 2 of the following are present: age >80 years, weight <60 kg, or serum creatinine >1.5 mg/dL. If cardioversion is immediate, a single starting dose of 10 mg (or 5 mg if the dose is down-titrated) of apixaban is administered. Cardioversion may be attempted up to 90 days after randomization. Patients are followed up for 30 days after cardioversion or 90 days postrandomization if cardioversion is not performed within that timeframe. Outcomes are stroke, systemic embolization, major bleeds, clinically relevant nonmajor bleeding, and death, all adjudication-blinded.

    Statistics: The warfarin-naive cohort from the ARISTOTLE study was considered the closest data set to the patients being recruited into this study. The predicted incidence of stroke, systemic embolism, and major bleeding within 30 days after randomization was approximately 0.75%. To adequately power for a noninferiority trial, approximately 48,000 participants would be needed, a number in excess of feasibility. The figure of 1,500 patients was considered clinically meaningful and achievable.

  • 29. Flather, Marcus D.
    et al.
    Babalis, Daphne
    Booth, Jean
    Bardaji, Alfredo
    Machecourt, Jacques
    Opolski, Grzegorz
    Ottani, Filippo
    Bueno, Hector
    Banya, Winston
    Brady, Anthony R.
    Bojestig, Mats
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Cluster-randomized trial to evaluate the effects of a quality improvement program on management of non-ST-elevation acute coronary syndromes: The European Quality Improvement Programme for Acute Coronary Syndromes (EQUIP-ACS)2011In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 162, no 4, p. 700-707.e1Article in journal (Refereed)
    Abstract [en]

    Background Registries have shown that quality of care for acute coronary syndromes (ACS) often falls below the standards recommended in professional guidelines. Quality improvement (QI) is a strategy to improve standards of clinical care for patients, but the efficacy of QI for ACS has not been tested in randomized trials. Methods We undertook a prospective, cluster-randomized, multicenter, multinational study to evaluate the efficacy of a QI program for ACS. Participating centers collected data on consecutive admissions for non-ST-elevation ACS for 4 months before the QI intervention and 3 months after. Thirty-eight hospitals in France, Italy, Poland, Spain, and the United Kingdom were randomized to receive the QI program or not, 19 in each group. We measured 8 in-hospital quality indicators (risk stratification, coronary angiography, anticoagulation, beta-blockers, statins, angiotensin-converting enzyme inhibitors, and clopidogrel loading and maintenance) before and after the intervention and compared composite changes between the QI and non-QI groups. Results A total of 2604 patients were enrolled. The absolute overall change in use of quality indicators in the QI group was 8.5% compared with 0.8% in the non-QI group (odds ratio for achieving a quality indicator in QI versus non-QI 1.66, 95% CI 1.43-1.94; P < .001). The main changes were observed in the use of risk stratification and clopidogrel loading dose. Conclusions The QI strategy resulted in a significant improvement in the quality indicators measured. This type of QI intervention can lead to useful changes in health care practice for ACS in a wide range of settings.

  • 30.
    Frigoli, Enrico
    et al.
    Univ Bern, Clin Trials Unit, Bern, Switzerland.
    Smits, Pieter
    Maasstad Hosp, Dept Cardiol, Rotterdam, Netherlands.
    Vranckx, Pascal
    Jessa Ziekenhuis, Hartcentrum Hasselt, Dept Cardiol & Crit Care Med, Hasselt, Belgium;Hasselt Univ, Fac Med & Life Sci, Hasselt, Belgium.
    Ozaki, Yokio
    Fujita Hlth Univ, Sch Med, Dept Cardiol, Toyoake, Aichi, Japan.
    Tijssen, Jan
    Univ Amsterdam, Acad Med Ctr, AMC Heartctr, Amsterdam, Netherlands.
    Juni, Peter
    Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, Appl Hlth Res Ctr, Toronto, ON, Canada.
    Morice, Marie-Claude
    CERC, Massy, France.
    Onuma, Yoshinobu
    Erasmus MC, Thorax Ctr, Rotterdam, Netherlands.
    Windecker, Stephan
    Bern Univ Hosp, Dept Cardiol, Bern, Switzerland.
    Frenk, Andre
    Bern Univ Hosp, Dept Cardiol, Bern, Switzerland.
    Spaulding, Christian
    Paris Descartes Univ, Hop Europeen Georges Pompidou, AP HP, INSERM,U 970,Sudden Death Expert Ctr,Cardiol Dept, Paris, France.
    Chevalier, Bernard
    Ramsay Gen Sante, Intervent Cardiol Dept, Inst Cardiovasc Paris Sud, Massy, France.
    Barbato, Emanuele
    Cardiovasc Res Ctr Aalst, Aalst, Belgium;Univ Federico II Naples, Dept Adv Biomed Sci, Div Cardiol, Naples, Italy.
    Tonino, Pim
    Catharina Hosp, Dept Cardiol, Eindhoven, Netherlands.
    Hildick-Smith, David
    Brighton & Sussex Univ Hosp NHSTrust, Brighton, E Sussex, England.
    Roffi, Marco
    Geneva Univ Hosp, Div Cardiol, Geneva, Switzerland.
    Kornowski, Ran
    Tel Aviv Univ, Sackler Sch Med, Rabin Med Ctr, Tel Aviv, Israel.
    Schultz, Carl
    Univ Western Australia, Royal Perth Hosp Campus, Dept Cardiol, Perth, WA, Australia.
    Lesiak, Maciej
    Univ Med Sci, Dept Cardiol 1, Poznan, Poland.
    Iniguez, Andres
    Hosp Alvaro Cunqueiro, Vigo, Spain.
    Colombo, Antonio
    IRCCS San Raffaele Sci Inst, Unit Cardiovasc Intervent, Milan, Italy.
    Alasnag, Mirvat
    King Fahad Armed Forces Hosp, Dept Cardiol, Jeddah, Saudi Arabia.
    Mullasari, Ajit
    Madras Med Mission, Chennai, Tamil Nadu, India.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Stankovic, Goran
    Univ Belgrade, Clin Ctr Serbia, Dept Cardiol, Belgrade, Serbia;Univ Belgrade, Fac Med, Belgrade, Serbia.
    Ong, Paul J. L.
    Tan Tock Seng Hosp, Singapore, Singapore.
    Rodriguez, Alfredo E.
    Otamendi Hosp, Buenos Aires Sch Med, Cardiac Unit, Cardiovasc Res Ctr CECI, Buenos Aires, DF, Argentina.
    Mahfoud, Felix
    Saarland Univ Hosp, Homburg, Germany.
    Bartunek, Jozef
    Bern Univ Hosp, Dept Cardiol, Bern, Switzerland.
    Moschovitis, Aris
    Bern Univ Hosp, Dept Cardiol, Bern, Switzerland.
    Laanmets, Peep
    North Estonia Med Ctr Fdn, Tallinn, Estonia.
    Leonardi, Sergio
    Fdn IRCCS Policlin San Matteo, Pavia, Italy.
    Heg, Dik
    Univ Bern, Clin Trials Unit, Bern, Switzerland.
    Sunnaker, Mikael
    Univ Bern, Clin Trials Unit, Bern, Switzerland.
    Valgimigli, Marco
    Bern Univ Hosp, Dept Cardiol, Bern, Switzerland.
    Design and rationale of the Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Standard DAPT Regimen (MASTER DAPT) Study2019In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 209, p. 97-105Article in journal (Refereed)
    Abstract [en]

    Background The optimal duration of antiplatelet therapy in high-bleeding risk (HBR) patients with coronary artery disease treated with newer-generation drug-eluting bioresorbable polymer-coated stents remains unclear. Design MASTER DAPT (clinicaltrial.gov NCT03023020) is an investigator-initiated, open-label, multicenter, randomized controlled trial comparing an abbreviated versus a standard duration of antiplatelet therapy after bioresorbable polymer-coated Ultimaster (TANSEI) sirolimus-eluting stent implantation in approximately 4,300 HBR patients recruited from >= 100 interventional cardiology centers globally. After a mandatory 30-day dual-antiplatelet therapy (DAPT) run-in phase, patients are randomized to (a) a single antiplatelet regimen until study completion or up to 5 months in patients with clinically indicated oral anticoagulation (experimental 1-month DAPT group) or (b) continue DAPT for at least 5 months in patients without or 2 in patients with concomitant indication to oral anticoagulation, followed by a single antiplatelet regimen (standard antipkitelet regimen). With a final sample size of 4,300 patients, this study is powered to assess the noninferiority of the abbreviated antiplatelet regimen with respect to the net adverse clinical and major adverse cardiac and cerebral events composite end points and if satisfied for the superiority of abbreviated as compared to standard antiplatelet therapy duration in terms of major or clinically relevant nonmajor bleeding. Study end points will be adjudicated by a blinded Clinical Events Committee. Conclusions The MASTER DAPT study is the first randomized controlled trial aiming at ascertaining the optimal duration of antiplatelet therapy in HBR patients treated with sirolimus-eluting bioresorbable polymer-coated stent implantation.

  • 31.
    Fröbert, Ole
    et al.
    Orebro Univ, Fac Hlth, Dept Cardiol, S-70185 Orebro, Sweden..
    Götberg, Matthias
    Univ Hosp Lund, Dept Cardiol, Lund, Sweden..
    Angerås, Oskar
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Jonasson, Lena
    Univ Hosp Linkoping, Dept Cardiol, Linkoping, Sweden..
    Erlinge, David
    Univ Hosp Lund, Dept Cardiol, Lund, Sweden..
    Engstrom, Thomas
    Univ Copenhagen, Dept Cardiol, Rigshosp, Copenhagen, Denmark..
    Persson, Jonas
    Karolinska Inst, Danderyd Univ Hosp, Dept Clin Sci, Stockholm, Sweden..
    Jensen, Svend E.
    Aalborg Univ Hosp, Dept Cardiol, Aalborg, Denmark..
    Omerovic, Elmir
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, 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.
    Nilsson, Johan
    Umea Univ, Dept Publ Hlth & Clin Med, Heart Ctr, Cardiol, Umea, Sweden..
    Kåregren, Amra
    Vesteras Cty Hosp, Dept Cardiol, Vasteras, Sweden..
    Moer, Rasmus
    Feiring Clin, Feiring, Norway..
    Yang, Cao
    Orebro Univ, Sch Med Sci, Clin Epidemiol & Biostat, Orebro, Sweden.;Karolinska Inst, Inst Evironmentol Med, Unit Biostat, Stockholm, Sweden..
    Agus, David B.
    Univ Southern Calif, Lawrence J Ellison Inst Transformat Med, Los Angeles, CA 90089 USA..
    Erglis, Andrejs
    Pauls Stradins Clin Univ Hosp, Latvian Ctr Cardiol, Riga, Latvia..
    Jensen, Lisette O.
    Odense Univ Hosp, Dept Cardiol, Odense, Denmark..
    Jakobsen, Lars
    Aarhus Univ Hosp, Dept Cardiol, Aarhus, Denmark..
    Christiansen, Evald H.
    Aarhus Univ Hosp, Dept Cardiol, Aarhus, Denmark..
    Pernow, John
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Cardiol Unit, Stockholm, Sweden..
    Design and rationale for the Influenza vaccination After Myocardial Infarction (IAMI) trial. A registry-based randomized clinical trial2017In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 189, p. 94-102Article in journal (Refereed)
    Abstract [en]

    Background: Registry studies and case-control studies have demonstrated that the risk of acute myocardial infarction (AMI) is increased following influenza infection. Small randomized trials, underpowered for clinical end points, indicate that future cardiovascular events can be reduced following influenza vaccination in patients with established cardiovascular disease. Influenza vaccination is recommended by international guidelines for patients with cardiovascular disease, but uptake is varying and vaccination is rarely prioritized during hospitalization for AMI.

    Methods/design: The Influenza vaccination After Myocardial Infarction (IAMI) trial is a double-blind, multicenter, prospective, registry-based, randomized, placebo-controlled, clinical trial. A total of 4,400 patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI undergoing coronary angiography will randomly be assigned either to in-hospital influenza vaccination or to placebo. Baseline information is collected from national heart disease registries, and follow-up will be performed using both registries and a structured telephone interview. The primary end point is a composite of time to all cause death, a new AMI, or stent thrombosis at 1 year.

    Implications: The IAMI trial is the largest randomized trial to date to evaluate the effect of in-hospital influenza vaccination on death and cardiovascular outcomes in patients with STEMI or non-STEMI. The trial is expected to provide highly relevant clinical data on the efficacy of influenza vaccine as secondary prevention after AMI.

  • 32. Fröbert, Ole
    et al.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Gudnason, Thorarinn
    Thuesen, Leif
    Svensson, Roger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Olivecrona, Göran K.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia (TASTE trial). A multicenter, prospective, randomized, controlled clinical registry trial based on the Swedish angiography and angioplasty registry (SCAAR) platform. Study design and rationale2010In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 160, no 6, p. 1042-1048Article in journal (Refereed)
    Abstract [en]

    Background In ST-elevation myocardial infarction (STEMI), distal embolization of thrombus material often precludes restoration of normal coronary artery flow. Small-scaled studies have demonstrated that intracoronary thrombus aspiration improves flow and myocardial perfusion, but only one larger randomized single-center study has suggested a survival benefit. Thrombus aspiration is widely used in clinical practice and is recommended by international guidelines despite limited evidence. Methods/design The Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia is a multicenter, prospective, randomized, controlled, clinical open-label trial based on the Swedish angiography and angioplasty registry (SCAAR) platform with blinded evaluation of end points. A total of 5,000 patients with STEMI undergoing primary percutaneous coronary intervention (PCI) will randomly be assigned either to conventional PCI or to thrombus aspiration followed by PCI. SCAAR will be used as the platform for randomization, allowing a broad population of all-comers in the registry network to be enrolled. All follow-up will also be done in SCAAR and other national registries. The primary end point is time to all-cause death at 30 days. Discussion The Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia trial is the largest trial to date to evaluate the effect of thrombus aspiration on death following PCI in patients with STEMI. We propose the term randomized clinical registry trial to describe the novel entity of using an online national registry as platform for case records, randomization, and follow-up.

  • 33. Fröbert, Ole
    et al.
    Scherstén, Fredrik
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Carlsson, Jörg
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Long-term safety and efficacy of drug-eluting and bare metal stents in saphenous vein grafts2012In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 164, no 1, p. 87-93Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Long-term safety and efficacy data of drug-eluting stents (DESs) in saphenous vein grafts (SVGs) are lacking. This study sought to compare the clinical outcomes of DES versus bare metal stents (BMS) in SVGs.

    METHODS:

    We studied all stent implantations in SVGs in Sweden during 74 months between 2005 and 2011 registered in the Swedish Coronary Angiography and Angioplasty Registry. We evaluated outcome in patients who received DES compared with those who received BMS after adjustments for differences in clinical, vessel, and lesion characteristics.

    RESULTS:

    Mean follow-up time was 3 years and 4 months. A total of 4,576 stents, implanted at 3,063 procedures, were included in the analysis of which 2,499 stents (54.6 %) were BMS and 2,077 (45.4%) were DES. The outcome analysis was based on 190 stent thromboses, 898 restenoses, and 523 deaths. The incidence of stent thrombosis did not differ between groups. When adjusted for baseline characteristics, including a propensity score for receiving DES, the incidence of restenosis was significantly lower with DES as compared with BMS (risk ratio 0.83, 95% CI 0.70-0.97, P = .019). There was a difference in mortality in the crude analysis between DES and BMS, and after multivariable adjustment, this difference remained statistically significant (risk ratio 0.80, CI 0.65-0.99, P = .038).

    CONCLUSIONS:

    The use of DES compared with BMS in SVGs was associated with a significantly lower adjusted incidence of restenosis and death in this large, national, all-encompassing propensity adjusted observational study.

  • 34. Garcia, David A.
    et al.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lopes, Renato D.
    Thomas, Laine
    Alexander, John H.
    Hylek, Elaine M.
    Ansell, Jack
    Hanna, Michael
    Lanas, Fernando
    Flaker, Greg
    Commerford, Patrick
    Xavier, Denis
    Vinereanu, Dragos
    Yang, Hongqiu
    Granger, Christopher B.
    Apixaban versus warfarin in patients with atrial fibrillation according to prior warfarin use: Results from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial2013In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 166, no 3, p. 549-558Article in journal (Refereed)
    Abstract [en]

    Background Patients with atrial fibrillation who are vitamin K antagonist (VKA)-naive may have a higher risk of thrombosis and/or bleeding than VKA-experienced patients. Methods and results Using data from ARISTOTLE, we assessed baseline characteristics and the treatment effect of apixaban versus warfarin in the VKA-naive and VKA-experienced cohorts. We compared rates of study drug discontinuation and time-in-therapeutic range. Overall, 7,800 (43%) were VKA naive, and 10,401 were VKA experienced. At baseline, both groups were similar with respect to age and congestive heart failure, hypertension, age, diabetes, stroke score (CHADS(2)). Fewer VKA-naive patients had a history of prior stroke (18% vs 21%) or prior bleeding (10% vs 22%) and were more often female (39% vs 33%). The effect of apixaban on the primary efficacy and safety outcomes was similar in VKA-naive (stroke/systemic embolism: hazard ratio [ HR] 0.86, 95% CI 0.67-1.11 and major bleeding: HR 0.73, 95% CI 0.59-0.91) and VKA-experienced populations (stroke/systemic embolism: HR 0.73, 95% CI 0.57-0.95, P value for interaction = 0.39 and major bleeding: HR 0.66, 95% CI 0.55-0.80, P value for interaction = 0.50). Permanent study drug discontinuation was numerically less likely in patients receiving apixaban whether they were VKA naive (HR for discontinuation: 0.87, 95% CI 0.79-0.95) or VKA experienced (HR for discontinuation: 0.93, 95% CI 0.85-1.02). Among patients receiving warfarin, the mean/median times in therapeutic range were lower in the VKA-naive group (VKA-naive: 57.5/61.4, VKA-experienced: 66.0/69.1, P < .001). Conclusion The treatment effects of apixaban (vs warfarin) were not modified by VKA naivety. The rates of stroke/systemic embolism and major bleeding were numerically lower among the patients assigned to apixaban, irrespective of prior VKA use.

  • 35. Giraldez, Roberto R.
    et al.
    Clare, Robert M.
    Lopes, Renato D.
    Dalby, Anthony J.
    Prabhakaran, Dorairaj
    Brogan, Gerard X., Jr.
    Giugliano, Robert P.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Tanguay, Jean-Francois
    Pollack, Charles V., Jr.
    Harrington, Robert A.
    Braunwald, Eugene
    Newby, L. Kristin
    Prevalence and clinical outcomes of undiagnosed diabetes mellitus and prediabetes among patients with high-risk non-ST-segment elevation acute coronary syndrome2013In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 165, no 6, p. 918-925.e2Article in journal (Refereed)
    Abstract [en]

    Background We examined the prevalence of undiagnosed diabetes or prediabetes and associations with ischemic outcomes among non-ST-segment elevation acute coronary syndrome (ACS) patients. Methods We categorized 8795 EARLY ACS trial patients into one of the following groups: "known diabetes" (n = 2860 [32.5%]; reported on the case report form), "undiagnosed diabetes" (n = 1069 [12.2%]; no diabetes history and fasting glucose >= 126 mg/dL or hemoglobin A(1c) >= 6.5%), "prediabetes" (n = 947 [10.8%]; fasting glucose >= 110 to <126 mg/dL, or " normal" (n = 3919 [44.5%]). Adjusted associations of known diabetes, undiagnosed diabetes, and prediabetes (versus normal) with 30-day and 1-year outcomes were determined. Results Undiagnosed diabetes was associated with greater 30-day death or myocardial infarction (MI) (ORadj 1.28, 95% CI 1.05-1.57), driven primarily by greater 30-day mortality (ORadj 1.65, 95% CI 1.09-2.48). Known diabetic patients had 30-day death or MI outcomes similar to those of normal patients, but 30-day mortality was higher (ORadj 1.40, 95% CI 1.01-1.93). Prediabetic patients had 30-day death or MI outcomes similar to those of normal patients. One-year mortality was greater among known diabetic patients (HRadj 1.38, 95% CI 1.13-1.67) but not among those with undiagnosed diabetes or prediabetes. Conclusions Undiagnosed diabetes and prediabetes were common among high-risk non-ST-segment elevation ACS patients. Routine screening for undiagnosed diabetes may be useful since these patients seem to have worse short-term outcomes and deserve consideration of alternative management strategies.

  • 36.
    Gotberg, Matthias
    et al.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, S-22185 Lund, Sweden..
    Christiansen, Evald H.
    Aarhus Univ Hosp, Dept Cardiol, Skejby, Denmark..
    Gudmundsdottir, Ingibjorg
    Reykjavik Univ Hosp, Dept Cardiol, Reykjavik, Iceland..
    Sandhall, Lennart
    Helsingborg Cty Hosp, Dept Radiol, Helsingborg, Sweden..
    Omerovic, Elmir
    Sahlgrenska Univ, Dept Cardiol, Gothenburg, 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.
    Erlinge, David
    Lund Univ, Skane Univ Hosp, Dept Cardiol, S-22185 Lund, Sweden..
    Frobert, Ole
    Univ Orebro, Fac Hlth, Dept Cardiol, SE-70182 Orebro, Sweden..
    Instantaneous Wave-Free Ratio versus Fractional Flow Reserve guided intervention (iFR-SWEDEHEART): Rationale and design of a multicenter, prospective, registry-based randomized clinical trial2015In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 170, no 5, p. 945-950Article in journal (Refereed)
    Abstract [en]

    Background Instantaneous wave-free ratio (iFR) is a new hemodynamic resting index for assessment of coronary artery stenosis severity. iFR uses high frequency sampling to calculate a gradient across a coronary lesion during a period of diastole. The index has been tested against fractional flow reserve (FFR) and found to have an overall classification agreement of 80% to 85%. Whether the level of disagreement is clinically relevant is unknown. Clinical outcome data on iFR are scarce. This study is a registry-based randomized clinical trial, which is a novel strategy using health quality registries as on-line platforms for randomization, case record forms, and follow-up. Design/Methods iFR-SWEDEHEART is a multicenter, prospective, randomized, controlled, clinical open-label clinical trial. Two thousand patients with stable angina or acute coronary syndrome and an indication for physiology-guided assessment of one or more coronary stenoses will be randomized 1: 1 to either iFR- or FFR-guided intervention. The randomization will be conducted online in the Swedish web-based system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies (SWEDEHEART) registry. The trial has a non-inferiority design, with a primary combined end point of all-cause death, non-fatal myocardial infarction, and unplanned revascularization at 12 months. End points will be identified through national registries and undergo central blind adjudication to ensure data quality. Discussion The iFR-SWEDEHEART trial is an registry-based randomized clinical trial evaluating the safety and efficacy of the diagnostic method iFR compared to FFR.

  • 37. Goto, Shinya
    et al.
    Zhu, Jun
    Liu, Lisheng
    Oh, Byung-Hee
    Wojdyla, Daniel M.
    Aylward, Philip
    Bahit, M. Cecilia
    Gersh, Bernard J.
    Hanna, Michael
    Horowitz, John
    Lopes, Renato D.
    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.
    Xavier, Denis
    Alexander, John H.
    Efficacy and Safety of Apixaban Compared with Warfarin for Stroke Prevention in Patients with Atrial Fibrillation from East Asia: A Subanalysis of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial2014In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 168, no 3, p. 303-309Article in journal (Refereed)
    Abstract [en]

    Background The perceived risk of serious bleeding is an obstacle to the use of oral anticoagulation in East Asia. The efficacy and safety of apixaban in East Asian patients with atrial fibrillation are unknown. Methods ARISTOTLE included 18,201 patients with nonvalvular atrial fibrillation randomized to apixaban 5 mg twice daily or warfarin. The efficacy and safety of apixaban and warfarin among patients recruited from East Asia (n = 1,993) were compared with those recruited from outside East Asia (n = 16,208). Results Compared with warfarin, apixaban resulted in a consistent reduction in stroke or systemic embolism in East Asian (hazard ratio [HR] 0.74, 95% CI 0.50-1.10) and non-East Asian (HR 0.81, 95% CI 0.66-0.99) patients (interaction P = .70). Consistent benefits of apixaban over warfarin were also seen for major bleeding in East Asian (HR 0.53, 95% CI 0.35-0.80) and non-East Asian (HR 0.72, 95% CI 0.62-0.83) patients (interaction P = .17). There was a greater reduction in major or clinically relevant nonmajor bleeding with apixaban compared with warfarin in East Asian (HR 0.49, 95% CI 0.35-0.67) than in non-East Asian (HR 0.71, 95% CI 0.63-0.79) patients (interaction P = .03). Numerically higher rates of intracranial bleeding were seen in East Asian patients with warfarin but not with apixaban. Conclusions Apixaban resulted in similar reductions in stroke or systemic embolism and major bleeding and greater reductions in major or clinically relevant nonmajor bleeding in patients from East Asia. Warfarin is associated with more intracranial bleeding, particularly in patients from East Asia.

  • 38. Granger, CB
    et al.
    Lopes, RD
    Hanna, Michael
    Ansell, Jack
    Hylek, Elaine M
    Alexander, John H
    Thomas, Laine
    Wang, J
    Bahit, M Cecilia
    Verheugt, Freek
    Lawrence, Jack
    Xavier, Denis
    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.
    Clinical events after transitioning from apixaban versus warfarin to warfarin at the end of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial2015In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 169, no 1, p. 25-30Article in journal (Refereed)
    Abstract [en]

    Background We sought to assess the occurrence of events after blinded study drug discontinuation and transition to open-label vitamin K antagonist (VKA) in ARISTOTLE.

    Methods At the end of ARISTOTLE, blinded study drug was stopped, and open-label VKA was recommended. For patients completing the trial on blinded study drug, a 2-day bridging period with apixaban or apixaban placebo was recommended (while beginning open-label VKA). Outcomes were assessed during the 30 days after stopping blinded study drug.

    Results Of the 6,809 patients in the apixaban group and 6,588 in the warfarin group who completed the trial on study drug, there were 21 strokes or systemic emboli (4.02%/year) and 26 major bleeding (4.97%/year) events in the apixaban group (transitioning to VKA) and 5 strokes or systemic emboli (0.99%/year) and 10 major bleeding (1.97%/year) events in the warfarin group (continuing on VKA), with most of the imbalance between groups being after the first week. Similar results were seen in the first 30 days of the trial where warfarin-naive patients starting warfarin had a higher rate of stroke or systemic emboli (5.41%/year) than warfarin-experienced patients (1.42%/year), a pattern not seen when starting apixaban. No similar increase in events with apixaban versus warfarin was seen during temporary or permanent study drug discontinuation during the trial.

    Conclusions The excess in thrombotic and bleeding events in the apixaban group after study drug discontinuation appears to be related to an increased risk associated with the initiation of a VKA rather than a direct effect of apixaban. Whether >= 2 days of apixaban bridging improves outcomes during VKA transition is unknown and deserves further evaluation.

  • 39.
    Grimfjärd, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Vasteras Hosp, Uppsala, Sweden..
    Erlinge, David
    Lund Univ, Skane Univ Hosp, Lund, Sweden..
    Koul, Sasha
    Lund Univ, Skane Univ Hosp, Lund, Sweden..
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, 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.
    Low real-world early stent thrombosis rates in ST-elevation myocardial infarction patients and the use of bivalirudin, heparin alone or glycoprotein IIb/IIIa inhibitor treatment: A nationwide Swedish registry report2016In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 176, p. 78-82Article in journal (Refereed)
    Abstract [en]

    Background In recent studies of primary percutaneous coronary intervention (PCI), bivalirudin compared with heparin has been associated with increased risk of stent thrombosis (ST). Our aim was to describe incidence and outcome of definite, early ST in a large contemporary primary PCI population divided in antithrombotic therapy subgroups. Methods and Results A prospective, observational cohort study of all 31,258 ST-elevation myocardial infarction patients who received a stent in Sweden from January 2007 to July 2014 in the SWEDEHEART registry was conducted. Patients were divided into 3 groups: bivalirudin, heparin alone, or glycoprotein IIb/IIIa inhibitor treated. Primary outcome measure was incidence of definite early ST (within 30 days of PCI). Secondary outcomes included all-cause mortality. Incidence of early ST was low, regardless of bivalirudin, heparin alone, or glycoprotein IIb/IIIa inhibitor treatment (0.84%, 0.94%, and 0.83%, respectively). All-cause mortality at 1 year was 20.7% for all ST patients (n = 265), compared with 9.1% in those without ST (n = 31,286; P < .001). Patients with ST days 2-30 had numerically higher all-cause mortality at 1 year compared with patients with ST days 0-1 (23% vs 16%, P =.20). Conclusion In this real-world observational study of 31,258 ST-elevation myocardial infarction patients, the incidence of early ST was low, regardless of antithrombotic treatment strategy. Early ST was associated with increased mortality. Numerically higher all-cause mortality at 1 year was noted with ST days 2-30 compared with ST days 0-1 post-PCI.

  • 40.
    Gudnadottir, Gudny Stella
    et al.
    Landspitali Univ Hosp, Reykjavik, Iceland.;Univ Iceland, Dept Cardiol, Reykjavik, Iceland.;Univ Iceland, Cardiovasc Res Ctr, Reykjavik, Iceland.;Sahlgrens Univ Hosp, Dept Geriatr, Gothenburg, Sweden..
    Andersen, Karl
    Landspitali Univ Hosp, Reykjavik, Iceland.;Univ Iceland, Dept Cardiol, Reykjavik, Iceland.;Univ Iceland, Cardiovasc Res Ctr, Reykjavik, Iceland..
    Thrainsdottir, Inga Sigurros
    Landspitali Univ Hosp, Reykjavik, Iceland.;Univ Iceland, Dept Cardiol, Reykjavik, Iceland.;Univ Iceland, Cardiovasc Res Ctr, Reykjavik, Iceland..
    James, Stefan Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Gudnason, Thorarinn
    Landspitali Univ Hosp, Reykjavik, Iceland.;Univ Iceland, Dept Cardiol, Reykjavik, Iceland.;Univ Iceland, Cardiovasc Res Ctr, Reykjavik, Iceland..
    Gender differences in coronary angiography, subsequent interventions, and outcomes among patients with acute coronary syndromes2017In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 191, p. 65-74Article in journal (Refereed)
    Abstract [en]

    Background The objective was to investigate whether gender disparities are found in referrals of patients with acute coronary syndromes to percutaneous coronary interventions (PCIs) or coronary artery bypass grafting (CABG) and, furthermore, to study gender differences in complications and mortality. Methods All consecutive coronary angiographies (CAs) and PCIs performed in Sweden and Iceland are prospectively registered in the Swedish Coronary Angiography and Angioplasty Registry. For the present analysis, data of patients with acute coronary syndromes, enrolled in 2007-2011, were used to analyze gender differences in revascularization, in-hospital complications, and 30-day mortality. Results A total of 106,881 CAs were performed during the study period. In patients with significant coronary artery disease, the adjusted odds ratio (OR) for women to undergo PCI compared with men was 0.95 (95% CI 0.92-0.99) and 0.81 (0.76-0.87) for referrals to CABG. In patients with 1-vessel disease, women were less likely to undergo PCI than men, but women with 2- or 3-vessel or left main stem disease were more likely to undergo PCI. All in-hospital complications after CA followed by PCI were more frequent among women (adjusted OR 1.58 [1.47-1.70]). There was no gender difference in adjusted 30-day mortality after PCI (1.02 [0.92-1.12]) and after CABG (0.97 [0.72-1.31]). Conclusions After CA showing 1-vessel disease, women as compared with men were less likely to undergo PCI. In the group with 2- or 3-vessel disease or left main stem stenosis, women were more likely to undergo PCI but less likely to undergo CABG. However, there was no gender difference in 30-day mortality.

  • 41.
    Gudnadottir, Gudny Stella
    et al.
    Sahlgrens Univ Hosp, Dept Geriatr, Gothenburg, Sweden;Landspitali Univ Hosp, Dept Cardiol, Reykjavik, Iceland;Landspitali Univ Hosp, Cardiovas Res Ctr, Reykjavik, Iceland;Univ Iceland, Sch Hlth Sci, Reykjavik, Iceland.
    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.
    Andersen, Karl
    Landspitali Univ Hosp, Dept Cardiol, Reykjavik, Iceland;Landspitali Univ Hosp, Cardiovas Res Ctr, Reykjavik, Iceland;Univ Iceland, Sch Hlth Sci, Reykjavik, Iceland.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Thrainsdottir, Inga Sigurros
    Landspitali Univ Hosp, Dept Cardiol, Reykjavik, Iceland;Landspitali Univ Hosp, Cardiovas Res Ctr, Reykjavik, Iceland.
    Ravn-Fischer, Annica
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Pfizer AB, Sollentuna, Sweden.
    Gudnason, Thorarinn
    Landspitali Univ Hosp, Dept Cardiol, Reykjavik, Iceland;Landspitali Univ Hosp, Cardiovas Res Ctr, Reykjavik, Iceland;Univ Iceland, Sch Hlth Sci, Reykjavik, Iceland.
    Outcomes after STEMI in old multimorbid patients with complex health needs and the effect of invasive management2019In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 211, p. 11-21Article in journal (Refereed)
    Abstract [en]

    Background: The aim of this study was to assess one-year outcomes of invasive and non-invasive strategies in ST-elevation myocardial infarction (STEMI) among multimorbid older people with complex health needs.

    Methods: We included patients, registered between 2006 and 2013 in the SWEDEHEART registry, who were 70 years old or older with STEMI, had multimorbidily and complex health needs and were discharged alive. The one-year outcomes of patients who underwent invasive strategy (examined with coronary angiography <= 14 days) were compared to those who did not. The primary event was a composite of all-cause death, admission due to new acute coronary syndrome, stroke or transient ischemic attack.

    Results: We identified patients, and 1089 were managed invasively and 570 non-invasively. The mean age was 79 years and 83 years in the 2 groups, respectively. After multivariable adjustment for baseline differences between the groups, including propensity scores, the primary event occurred in 31% of patients in the invasive group and 55% in the non-invasive group, adjusted hazard ratio (95% confidence intervals): 0.67 (0.54-0.83). One-year mortality was 18% in the invasive group and 45% in the non-invasive group, adjusted hazard ratio 0.51 (0.39-0.65).

    Conclusions: Multimorbid older people with complex health needs and STEMI had high rates of new ischemic events and death. In this cohort of older, high risk STEMI patients, an invasive strategy was associated with lower event rates. Randomized studies are needed to clarify whether these high risk patients who might benefit from invasive care are being managed too conservatively.

  • 42. Guimarães, Patrícia O
    et al.
    Leonardi, Sergio
    Huang, Zhen
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    de Werf, Frans Van
    Aylward, Philip E
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Harrington, Robert A
    Moliterno, David J
    Armstrong, Paul W
    White, Harvey D
    Alexander, Karen P
    Lopes, Renato D
    Mahaffey, Kenneth W
    Tricoci, Pierluigi
    Clinical features and outcomes of patients with type 2 myocardial infarction: Insights from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial2018In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 196, p. 28-35Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Type 2 myocardial infarction (MI) is characterized by an imbalance between myocardial blood supply and demand, leading to myocardial ischemia without coronary plaque rupture, but its diagnosis is challenging.

    METHODS: In the TRACER trial, patients with non-ST-segment elevation acute coronary syndromes were included. We aimed to describe provoking factors, cardiac biomarker profiles, treatment patterns, and clinical outcomes of patients with type 2 MIs. MI events during trial follow-up were adjudicated by an independent clinical events classification committee (CEC) and were classified according to the Third Universal Definition of MI. Using available source documents retrieved as part of the CEC process, we performed a retrospective chart abstraction to collect details on the type 2 MIs. Cox regression models were used to explore the association between MI type (type 1 or type 2) and cardiovascular death.

    RESULTS: Overall, 10.3% (n=1327) of TRACER participants had a total of 1579 adjudicated MIs during a median follow-up of 502 days (25th and 75th percentiles [IQR] 349-667). Of all MIs, 5.2% (n=82) were CEC-adjudicated type 2 MIs, occurring in 76 patients. The incidence of type 2 MI was higher in the first month following randomization, after which the distribution became more scattered. The most frequent potential provoking factors for type 2 MIs were tachyarrhythmias (38.2%), anemia/bleeding (21.1%), hypotension/shock (14.5%), and hypertensive emergencies (11.8%). Overall, 36.3% had a troponin increase >10× the upper limit of normal. Coronary angiography was performed in 22.4% (n=17) of patients during hospitalizations due to type 2 MIs. The hazard of cardiovascular death was numerically higher following type 2 MI (vs. no MI, adj. HR 11.82, 95% CI 5.71-24.46; P<.0001) than that of type 1 MI (vs. no MI, adj. HR 8.90, 95% CI 6.93-11.43; P<.0001).

    CONCLUSIONS: Type 2 MIs were more prevalent in the first month after ACS, were characterized by the presence of triggers and infrequent use of an invasive strategy, and were associated with a high risk of death. Further efforts are needed to better define the role and implications of type 2 MI in both clinical practice and research.

  • 43. Harrington, Robert A.
    et al.
    Van de Werf, Frans
    Armstrong, Paul W.
    Aylward, Phil
    Veltri, Enrico
    Mahaffey, Kenneth W.
    Moliterno, David J.
    Strony, John
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    White, Harvey D.
    Diaz, Rafael
    Huber, Kurt
    Nicolau, Jose Carlos
    Carlos Prieto, Juan
    Isaza, Daniel
    Widimsky, Petr
    Grande, Peer
    Nieminen, Markku
    Montalescot, Gilles
    Bode, Christoph
    Wong, Lawrence
    Ofner, Peter
    Lewis, Basil S.
    Ambrosio, Giuseppe
    Valgimigli, Marco
    Ogawa, Hisao
    Yamaguchi, Jun-ichi
    Jukema, J. Wouter
    Cornel, Jan H.
    Nordrehaug, Jan Erik
    Ruzyllo, Witold
    Providencia, Luis
    Tan, Huay-Cheem
    Dalby, Anthony
    Seung-Jung, Park
    Betriu, Amadeo
    Cequier, Angel
    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.
    Pfisterer, Mathias
    Ming-Fong, Chen
    Timurkaynak, Timur
    Storey, Robert F.
    Chen, Edmond
    Hudson, Michael P.
    Lincoff, A. Michael
    Morrow, David A.
    Tricoci, Pierluigi
    Whellan, David
    The Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA.CER) trial: study design and rationale2009In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 158, no 3, p. 327-334Article in journal (Refereed)
    Abstract [en]

    Background The protease-activated receptor 1 (PAR-1), the main platelet receptor for thrombin, represents a novel target for treatment of arterial thrombosis, and SCH 530348 is an orally active, selective, competitive PAR-1 antagonist. We designed TRA.CER to evaluate the efficacy and safety of SCH 530348 compared with placebo in addition to standard of care in patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS) and high-risk features. Trial design TRA.CER is a prospective, randomized, double-blind, multicenter, phase III trial with an original estimated sample size of 10,000 subjects. Our primary objective is to demonstrate that SCH 530348 in addition to standard of care will reduce the incidence of the composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization compared with standard of care alone. Our key secondary objective is to determine whether SCH 530348 will reduce the composite of cardiovascular death, MI, or stroke compared with standard of care alone. Secondary objectives related to safety are the composite of moderate and severe GUSTO bleeding and clinically significant TIMI bleeding. The trial will continue until a predetermined minimum number of centrally adjudicated primary and key secondary end point events have occurred and all subjects have participated in the study for at least I year. The TRA.CER trial is part of the large phase III SCH 530348 development program that includes a concomitant evaluation in secondary prevention. Conclusion TRA.CER will define efficacy and safety of the novel platelet PAR-1 inhibitor SCH 530348 in the treatment of high-risk patients with NSTE ACS in the setting of current treatment strategies.

  • 44. Hedberg, Pär
    et al.
    Lönnberg, Ingemar
    Jonason, Tommy
    Nilsson, Göran
    Pehrsson, Kenneth
    Ringqvist, Ivar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Electrocardiogram and B-type natriuretic peptide as screening tools for left ventricular systolic dysfunction in a population-based sample of 75-year-old men and women2004In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 148, no 3, p. 524-529Article in journal (Refereed)
    Abstract [en]

    Background: Plasma concentration of B-type natriuretic peptide (BNP) has been suggested as a powerful screening tool for left ventricular systolic dysfunction. However, there are reports indicating that the 12-lead electrocardiogram (ECG) could be just as powerful. We aimed to evaluate the 12-lead ECG and BNP as screening tools for left ventricular systolic dysfunction in an elderly, unselected population.

    Methods: In a randomly selected population-based sample of 75-year-old men and women (n = 407), diagnostic characteristics were evaluated for the ECG and plasma concentration of BNP to detect left ventricular systolic dysfunction.

    Results: Sensitivity, specificity, and negative and positive predictive values for the ECG to detect left ventricular systolic dysfunction were 96%, 79%, 100%, and 26%, respectively. The corresponding values for the BNP (cut-off value 28 pg/mL) were 93%, 55%, 99%, and 13%. In participants without major abnormalities in the ECG, left ventricular systolic dysfunction was found in <1% (1/302), irrespective of BNP concentrations. In participants with abnormal ECGs, systolic dysfunction was more prevalent in persons with abnormal BNP concentrations than in those with normal concentrations (35% vs 3%, difference 32%, 95%CI for the difference 16%–44%)

    Conclusions: In 75-year-old subjects both the ECG and the plasma concentration of BNP are highly efficient in excluding left ventricular systolic dysfunction. However, compared with the BNP, the ECG yields a lower number of false positive cases. In screening for left ventricular systolic dysfunction, the BNP has a diagnostic value in addition to the ECG, but only in individuals with abnormal ECGs.

  • 45.
    Held, Claes
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    White, Harvey D
    Stewart, Ralph A H
    Davies, Richard
    Sampson, Shani
    Chiswell, Karen
    Silverstein, Adam
    Lopes, Renato D
    Heldestad, Ulrika
    Budaj, Andrzej
    Mahaffey, Kenneth W
    Wallentin, Lars C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Characterization of cardiovascular clinical events and impact of event adjudication on the treatment effect of darapladib versus placebo in patients with stable coronary heart disease: Insights from the STABILITY trial2018In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 208, p. 65-73, article id S0002-8703(18)30306-5Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Clinical Endpoint Classification (CEC) in clinical trials allows FOR standardized, systematic, blinded, and unbiased adjudication of investigator-reported events. We quantified the agreement rates in the STABILITY trial on 15,828 patients with stable coronary heart disease.

    METHODS: Investigators were instructed to report all potential events. Each reported event was reviewed independently by 2 reviewers according to prespecified processes and prespecified end point definitions. Concordance between reported and adjudicated cardiovascular (CV) events was evaluated, as well as event classification influence on final study results.

    RESULTS: In total, CEC reviewed 7,096 events: 1,064 deaths (696 CV deaths), 958 myocardial infarctions (MI), 433 strokes, 182 transient ischemic attacks, 2,052 coronary revascularizations, 1,407 hospitalizations for unstable angina, and 967 hospitalizations for heart failure. In total, 71.8% events were confirmed by CEC. Concordance was high (>80%) for cause of death and nonfatal MI and lower for hospitalization for unstable angina (25%) and heart failure (50%). For the primary outcome (composite of CV death, MI, and stroke), investigators reported 2,086 events with 82.5% confirmed by CEC. The STABILITY trial treatment effect of darapladib versus placebo on the primary outcome was consistent using investigator-reported events (hazard ratio 0.96 [95% CI 0.87-1.06]) or adjudicated events (hazard ratio 0.94 [95% CI 0.85-1.03]).

    CONCLUSIONS: The primary outcome results of the STABILITY trial were consistent whether using investigator-reported or CEC-adjudicated events. The proportion of investigator-reported events confirmed by CEC varied by type of event. These results should help improve event identification in clinical trials to optimize ascertainment and adjudication.

  • 46.
    Hess, Connie N.
    et al.
    Univ Colorado, Sch Med, Dept Med, Div Cardiol, Aurora, CO USA..
    Clare, Robert M.
    Duke Clin Res Inst, 2400 Pratt St,Rm 031 1 Terrace Level, Durham, NC 27705 USA..
    Neely, Megan L.
    Duke Clin Res Inst, 2400 Pratt St,Rm 031 1 Terrace Level, Durham, NC 27705 USA..
    Tricoci, Pierluigi
    Duke Clin Res Inst, 2400 Pratt St,Rm 031 1 Terrace Level, Durham, NC 27705 USA.;Duke Univ, Sch Med, Dept Med, Div Cardiol, Durham, NC 27706 USA..
    Mahaffey, Kenneth W.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alexander, John H.
    Duke Clin Res Inst, 2400 Pratt St,Rm 031 1 Terrace Level, Durham, NC 27705 USA.;Duke Univ, Sch Med, Dept Med, Div Cardiol, Durham, NC 27706 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.
    Lopes, Renato D.
    Duke Clin Res Inst, 2400 Pratt St,Rm 031 1 Terrace Level, Durham, NC 27705 USA.;Duke Univ, Sch Med, Dept Med, Div Cardiol, Durham, NC 27706 USA..
    Fox, Keith A. A.
    British Heart Fdn, Univ Edinburgh, Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland..
    White, Harvey D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand..
    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.
    Armstrong, Paul W.
    Univ Alberta, Div Cardiol, Edmonton, AB, Canada..
    Harrington, Robert A.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    Ohman, Erik Magnus
    Duke Clin Res Inst, 2400 Pratt St,Rm 031 1 Terrace Level, Durham, NC 27705 USA.;Duke Univ, Sch Med, Dept Med, Div Cardiol, Durham, NC 27706 USA..
    Roe, Matthew T.
    Duke Clin Res Inst, 2400 Pratt St,Rm 031 1 Terrace Level, Durham, NC 27705 USA.;Duke Univ, Sch Med, Dept Med, Div Cardiol, Durham, NC 27706 USA..
    Differential occurrence, profile, and impact of first recurrent cardiovascular events after an acute coronary syndrome2017In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 187, p. 194-203Article in journal (Refereed)
    Abstract [en]

    Objective Acute coronary syndrome (ACS) trials typically use a composite primary outcome (myocardial infarction [MI], stroke, or cardiovascular death), but differential patient characteristics, timing, and consequences associated with individual component end points as first events have not been well studied. We compared patient characteristics and prognostic significance associated with first cardiovascular events in the post-ACS setting for initially stabilized patients. Methods We combined patient-level data from 4 trials of post-ACS antithrombotic therapies (PLATO, APPRAISE-2, TRACER, and TRILOGY ACS) to characterize the timing of and characteristics associated with first cardiovascular events (MI, stroke, or cardiovascular death). Landmark analysis at 7 days after index ACS presentation was used to focus on spontaneous, postdischarge events that were not confounded by in-hospital procedural complications. Using a competing risk framework, we tested for differential associations between prespecified covariates and the occurrence of nonfatal stroke vs MI as the first event, and we examined subsequent events after the first nonfatal event. Results Among 46,694 patients with a median follow-up of 358 (25th, 75th percentiles 262, 486) days, a first ischemic event occurred in 4,307 patients (9.2%) as follows: MI in 5.8% (n = 2,690), stroke in 1.0% (n = 477), and cardiovascular death in 2.4% (n = 1,140). Older age, prior stroke/transient ischemic attack, prior atrial fibrillation, and higher diastolic blood pressure were associated with a significantly greater risk of stroke vs MI, whereas prior percutaneous coronary intervention was associated with a greater risk of MI vs stroke. Second events occurred in 32% of those with a first nonfatal stroke at a median of 13 (3, 59) days after the first event and in 32% of those with a first nonfatal MI at a median of 35 (5, 137) days after the first event. The most common second event was a recurrent MI among those with MI as the first event and cardiovascular death among those with stroke as the first event. Conclusions Approximately 9% of patients experienced a first cardiovascular event in the post-ACS setting during a median follow-up of 1 year. Although the profile and prognostic implications of stroke vs MI as the first nonfatal event differ substantially, approximately one-third of these patients experienced a second event, typically soon after the first event. These findings have implications for improving post-ACS care and influencing the design of future cardiovascular trials.

  • 47.
    Hijazi, Ziad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hohnloser, Stefan H.
    Goethe Univ Frankfurt, Dept Cardiol, Frankfurt, Germany.
    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.
    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.
    Eikelboom, John W.
    Populat Hlth Res Inst, Hamilton, ON, Canada.
    Ezekowitz, Michael D.
    Thomas Jefferson Med Coll, Wynnewood, PA USA;Heart Ctr, Wynnewood, PA USA.
    Reilly, Paul A.
    Boehringer Ingelheim Pharmaceut, Ridgefield, CT USA.
    Yusuf, Salim
    Populat Hlth Res Inst, Hamilton, ON, Canada.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Efficacy and safety of dabigatran compared with warfarin in patients with atrial fibrillation in relation to renal function over time-A RE-LY trial analysis2018In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 198, p. 169-177Article in journal (Refereed)
    Abstract [en]

    Background: Renal function may decline over time, and the efficacy and safety of dabigatran in atrial fibrillation (AF) in relation to renal function changes are unknown.& para;& para;Methods: The RE-LY trial randomized 18,113 patients with AF to 2 doses of dabigatran or warfarin for stroke prevention. Serial creatinine measurements were available in 16,988 patients. The relations between treatment, outcomes, and renal function (Cockcroft-Gault) were investigated using Cox-regression (1) with renal function as a time-dependent covariate and (2) according to worsening renal function (WRF) during follow-up, predefined as a decline in estimated glomerular filtration rate >20% from baseline.& para;& para;Results: During a median follow-up of 1.8 years, 4,106 (24.2%) participants were observed to have WRF, and 12,882 (75.8%) had stable renal function. The risks of all-cause mortality and major bleeding were higher in patients with WRF versus those with stable renal function (hazard ratio [95% CI]: 2.17 [1.81-2.59] and 1.43 [1.19-1.71]. respectively; both P < .0005). The efficacy and safety of dabigatran versus warfarin were similar irrespective of renal function changes over time (interaction P values >= .13 in both models). Dabigatran 110 mg showed a greater relative risk reduction of major bleeding in patients with normal renal function (estimated glomerular filtration rate >80 mL/min) during follow-up (interaction P= .026).& para;& para;Conclusions: In AF, WRF was associated with a higher risk of death and major bleeding. The efficacy and safety profile of dabigatran compared with warfarin was similar irrespective of renal function changes over time. Dabigatran 110 mg showed a greater relative risk reduction of major bleeding in patients with normal renal function during follow-up.

  • 48.
    Hijazi, Ziad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Connolly, Stuart J
    Eikelboom, John W
    Ezekowitz, Michael D
    Reilly, Paul A
    Yusuf, Salim
    Siegbahn, Agneta
    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, 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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Growth-differentiation factor 15 and risk of major bleeding in atrial fibrillation: Insights from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial2017In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 190, p. 94-103, article id S0002-8703(17)30172-2Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate and validate the prognostic value of growth-differentiation factor 15 (GDF-15) beyond clinical characteristics and other biomarkers concerning bleeding and stroke outcomes in patients with atrial fibrillation in the RE-LY trial.

    METHODS: GDF-15 was measured in samples collected at randomization in 8,474 patients with a median follow-up time of 1.9 years. Patients were stratified based on predefined GDF-15 cutoffs: group 1, <1,200 ng/L (the 90th percentile in healthy individuals); group 2, 1,200-1,800; and group 3, >1,800 ng/L (high-risk individuals). Efficacy and safety outcomes were compared across groups of GDF-15 in Cox models adjusted for baseline characteristics, cardiac (N-terminal pro-b-type natriuretic peptide, high-sensitive troponin T), inflammatory (interleukin 6, C-reactive protein) and coagulation (D-dimer) biomarkers, and randomized treatment.

    RESULTS: GDF-15 concentrations were <1,200 ng/L in 2,647 (31.2%), between 1,200 and 1,800 ng/L in 2,704 (31.9%), and >1,800 ng/L in 3,123 (36.9%) participants, respectively. Annual rates of stroke, major bleeding, and mortality increased with higher GDF-15 levels. The prognostic value of GDF-15 was independent of clinical characteristics for these outcomes. In models also adjusted for biomarkers, GDF-15 remained significantly associated with major bleeding (hazard ratio [95% CI] group 3 vs group 1 1.76 [1.28-2.42], P < .0005) and all-cause mortality (hazard ratio 1.72 [1.30-2.29], P < .0005). GDF-15 improved the c index of both the HAS-BLED (0.62-0.69) and ORBIT (0.68-0.71) bleeding risk scores.

    CONCLUSIONS: In patients with atrial fibrillation, GDF-15 is an independent risk indicator for major bleeding and all-cause mortality, but not for stroke. Therefore, GDF-15 seems useful as a specific marker of bleeding in patients with AF on oral anticoagulant treatment.

  • 49.
    Hjort, Marcus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Baron, Tomasz
    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.
    Jernberg, Tomas
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet.
    Tornvall, Per
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet.
    Eggers, Kai M.
    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.
    Prognosis in relation to high-sensitivity cardiac troponin T levels in patients with myocardial infarction and non-obstructive coronary arteries2018In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 200, p. 60-66Article in journal (Refereed)
    Abstract [en]

    Background: Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) is a recently recognized condition where biomarkers and prognosis are less well studied than in MI with obstructive coronary artery disease (MI-CAD). We therefore aimed to investigate the one-year prognostic value of high-sensitivity cardiac troponin T (hs-cTnT) levels in MINOCA in comparison to MI-CAD.

    Methods: In this registry-based cohort study, we used data frompatientswith a discharge diagnosis ofMI, admitted between 2009 and 2013 to Swedish hospitals using the hs-cTnT assay. Only patients without previously known coronary artery disease were considered. Patients with and without coronary stenosis N50% were regarded to haveMI-CAD andMINOCA, respectively. Assessed outcomes included all-cause mortality, cardiovascular (CV) mortality and major CV events (MACE), defined as the composite of CV death or admissions for nonfatal MI, heart failure (HF) or ischemic stroke.

    Results: The study cohort consisted of 1639 MINOCA and 17,304 MI-CAD patients. In adjusted analyses, hs-cTnT (ln) in MINOCA patients predicted all-cause mortality (HR 1.32 [95% CI 1.11-1.56]), CVmortality (HR 2.11 [95% CI 1.51-2.96]) and MACE (HR 1.44 [95% CI 1.20-1.72]). Hs-cTnT (ln) also predicted readmissions for HF (HR 1.51 [95% CI 1.51-2.96]) but not non-fatal MI or stroke. Interaction analyses suggested that hs-cTnT (ln) was at least as prognostic in patients with MINOCA compared to MI-CAD.

    Conclusions: Hs-cTnT levels inMINOCA patients are strong and independent predictors of adverse outcome. Consideration of hs-cTnT levels is important for risk assessment of MINOCA patients.

  • 50. Hofmann, Robin
    et al.
    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.
    Svensson, Leif
    Witt, Nils
    Frick, Mats
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Östlund, Ollie
    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.
    Ekelund, Ulf
    Erlinge, David
    Herlitz, Johan
    Jernberg, Tomas
    DETermination of the role of OXygen in suspected Acute Myocardial Infarction trial2014In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 167, no 3, p. 322-328Article in journal (Refereed)
    Abstract [en]

    Background The use of supplemental oxygen in the setting of suspected acute myocardial infarction (AMI) is recommended in international treatment guidelines and established in prehospital and hospital clinical routine throughout the world. However, to date there is no conclusive evidence from adequately designed and powered trials supporting this practice. Existing data are conflicting and fail to clarify the role of supplemental oxygen in AMI. Methods A total of 6,600 normoxemic (oxygen saturation [SpO2] >= 90%) patients with suspected AMI will be randomly assigned to either supplemental oxygen 6 L/min delivered by Oxymask (MedCore Sweden AB, Kista, Sweden) for 6 to 12 hours in the treatment group or room air in the control group. Patient inclusion and randomization will take place at first medical contact, either before hospital admission or at the emergency department. The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registry will be used for online randomization, allowing inclusion of a broad population of all-comers. Follow-up will be carried out in nationwide health registries and Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies. The primary objective is to evaluate whether oxygen reduces 1-year all-cause mortality. Secondary end points include 30-day mortality, major adverse cardiac events, and health economy. Prespecified subgroups include patients with confirmed AMI and certain risk groups. In a 3-month pilot study, the study concept was found to be safe and feasible. Conclusion The need to clarify the uncertainty of the role of supplemental oxygen therapy in the setting of suspected AMI is urgent. The DETO2X-AMI trial is designed and powered to address this important issue and may have a direct impact on future recommendations.

123 1 - 50 of 114
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf