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  • 1.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Daniela, Mariosa
    Adami, Hans-Olov
    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.
    Ingelsson, Erik
    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, Molecular epidemiology.
    Lagerros, Ylva Trolle
    Nyren, Olof
    Ye, Weimin
    Bellocco, Rino
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Dose–Response Relationship of Total and Leisure Time Physical Activity to Risk of Heart Failure: a prospective cohort study2014In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 7, no 5, p. 16p. 701-708Article in journal (Refereed)
    Abstract [en]

    Background—The nature of the association between levels of physical activity and risk of heart failure is little known. We investigated nonlinear associations of total and leisure time physical activity with risk of heart failure.

    Methods and Results—In 1997, 39 805 persons without heart failure completed a questionnaire of lifestyle factors and medical history. We used Cox regression models to investigate total (adjusting for education and previous myocardial infarction) and direct (multivariable-adjusted) effects of self-reported total and leisure time physical activity on risk of heart failure of any cause and heart failure of nonischemic origin. Heart failure diagnoses were obtained until December 31, 2010. Higher leisure time physical activity was associated with lower risk of heart failure of any cause; hazard ratio of the total effect of leisure time physical activity was for fifth versus first quintile 0.54; 95% confidence interval was 0.44 to 0.66. The direct effect was similar. High total daily physical activity level was associated with lower risk of heart failure, although the effect was less pronounced than for leisure time physical activity (total effect hazard ratio, 0.81; 95% confidence interval, 0.69–0.95; fifth versus first quintile). A similar direct effect observed.

    Conclusions—Leisure time physical activity was inversely related to risk of developing heart failure in a dose–response fashion. This was reflected in a similar but less pronounced association of total physical activity with risk of heart failure. Only part of the effects appeared to be mediated by traditional risk factors.

  • 2.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Farahmand, Bahman
    Ahlbom, Anders
    Held, Claes
    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.
    Ljunghall, Sverker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Risk of arrhythmias in 52 755 long-distance cross-country skiers: a cohort study2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no 47, p. 3624-3631Article in journal (Refereed)
    Abstract [en]

    AIMS:

    We aimed to investigate the association of number of completed races and finishing time with risk of arrhythmias among participants of Vasaloppet, a 90 km cross-country skiing event.

    METHODS AND RESULTS:

    All the participants without cardiovascular disease who completed Vasaloppet during 1989-98 were followed through national registries until December 2005. Primary outcome was hospitalization for any arrhythmia and secondary outcomes were atrial fibrillation/flutter (AF), bradyarrhythmias, other supraventricular tachycardias (SVT), and ventricular tachycardia/ventricular fibrillation/cardiac arrest (VT/VF/CA). Among 52 755 participants, 919 experienced arrhythmia during follow-up. Adjusting for age, education, and occupational status, those who completed the highest number of races during the period had higher risk of any arrhythmias [hazard ratio (HR)1.30; 95% CI 1.08-1.58; for ≥5 vs. 1 completed race], AF (HR 1.29; 95% CI 1.04-1.61), and bradyarrhythmias (HR 2.10; 95% CI 1.28-3.47). Those who had the fastest relative finishing time also had higher risk of any arrhythmias (HR 1.30; 95% CI 1.04-1.62; for 100-160% vs. >240% of winning time), AF (1.20; 95% CI 0.93-1.55), and bradyarrhythmias (HR 1.85; 95% CI 0.97-3.54). SVT or VT/VF/CA was not associated with finishing time or number of completed races.

    CONCLUSIONS:

    Among male participants of a 90 km cross-country skiing event, a faster finishing time and a high number of completed races were associated with higher risk of arrhythmias. This was mainly driven by a higher incidence of AF and bradyarrhythmias. No association with SVT or VT/VF/CA was found.

  • 3.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    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.
    Neovius, Martin
    Tynelius, Per
    Rasmussen, Finn
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Exercise capacity and muscle strength and risk of vascular disease and arrhythmias: A cohort study of 1.26 million young menManuscript (preprint) (Other academic)
    Abstract [en]

    Background:

    While physical activity and exercise protects against cardiovascular disease, athletes have higher risk of atrial fibrillation and other arrhythmias. Graded independent and joint influences of exercise capacity and muscle strength on these diseases are unknown.

    Methods:

    All 1.26 million Swedish men who participated in mandatory military conscription between 1972 and 1995 (at a median age of 18.2 years) contributed. Multivariable-adjusted Cox proportional hazards models were used to evaluate the associations of maximal exercise capacity and muscle strength at conscription to subsequent risk of vascular disease and arrhythmias, as identified in national registries.

    Results:

    During a median follow-up of 26.3 years, about 26,000 hospitalizations for vascular disease events and 17,000 for arrhythmias occurred. Exercise capacity was inversely associated with risk of vascular disease (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.61-0.67]; for 5th vs. 1st quintile) and so was muscle strength (HR 0.79; 0.76-0.83; for 5th vs. 1st quintile ). Similar associations were seen across a range of major vascular disease events. Exercise capacity was associated with incidence of arrhythmias in a U-shaped fashion (HR 0.91; 0.86-0.96; for 3rd vs. 1st quintile, and 0.99; 0.94-1.04; for 5th vs. 1st quintile). Higher muscle strength was associated with lower risk of arrhythmias (HR 0.87; 0.83-0.91; for 5th vs. 1st quintile). 

    Conclusion:

    Exercise capacity and muscle strength in late adolescence are independently and jointly associated with long-term risk of vascular disease and arrhythmias. The lower risk of vascular events with higher exercise capacity was not outweighed by higher risk of arrhythmias.

  • 4.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Mariosa, D.
    Adami, H. O.
    Held, Claes
    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.
    Ingelsson, E.
    Lagerros, Y.
    Nyren, O.
    Weimin, Y.
    Bellocco, R.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Total and leisure time physical activity and risk of heart failure: a prospective cohort study2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no Suppl 1, p. 1052-1052Article in journal (Other academic)
  • 5.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Rasmussen, Finn
    Karolinska Inst, Dept Publ Hlth Sci, Child & Adolescent Publ Hlth Epidemiol Unit, Stockholm, Sweden..
    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.
    Neovius, Martin
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden..
    Tynelius, Per
    Karolinska Inst, Dept Publ Hlth Sci, Child & Adolescent Publ Hlth Epidemiol Unit, Stockholm, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Exercise capacity and muscle strength and risk of vascular disease and arrhythmia in 1.1 million young Swedish men: cohort study2015In: BMJ-BRITISH MEDICAL JOURNAL, ISSN 1756-1833, Vol. 351, article id h4543Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To investigate the associations of exercise capacity and muscle strength in late adolescence with risk of vascular disease and arrhythmia. DESIGN Cohort study. SETTING General population in Sweden. PARTICIPANTS 1.1 million men who participated in mandatory military conscription between 1 August 1972 and 31 December 1995, at a median age of 18.2 years. Participants were followed until 31 December 2010. MAIN OUTCOMES Associations between exercise capacity and muscle strength with risk of vascular disease and subgroups (ischaemic heart disease, heart failure, stroke, and cardiovascular death) and risk of arrhythmia and subgroups (atrial fibrillation or flutter, bradyarrhythmia, supraventricular tachycardia, and ventricular arrhythmia or sudden cardiac death). Maximum exercise capacity was estimated by the ergometer bicycle test, and muscle strength was measured as handgrip strength by a hand dynamometer. High exercise capacity or muscle strength was deemed as above the median level. RESULTS During a median follow-up of 26.3 years, 26 088 vascular disease events and 17 312 arrhythmia events were recorded. Exercise capacity was inversely associated with risk of vascular disease and its subgroups. Muscle strength was also inversely associated with vascular disease risk, driven by associations of higher muscle strength with lower risk of heart failure and cardiovascular death. Exercise capacity had a U shaped association with risk of arrhythmia, driven by a direct association with risk of atrial fibrillation and a U shaped association with bradyarrhythmia. Higher muscle strength was associated with lower risk of arrhythmia (specifically, lower risk of bradyarrhythmia and ventricular arrhythmia). The combination of high exercise capacity and high muscle strength was associated with a hazard ratio of 0.67 (95% confidence interval 0.65 to 0.70) for vascular events and 0.92 (0.88 to 0.97) for arrhythmia compared with the combination of low exercise capacity and low muscle strength. CONCLUSIONS Exercise capacity and muscle strength in late adolescence are independently and jointly associated with long term risk of vascular disease and arrhythmia. The health benefit of lower risk of vascular events with higher exercise capacity was not outweighed by higher risk of arrhythmia.

  • 6. Armaganijan, Luciana
    et al.
    Lopes, Renato
    Huang, Zhen
    Tricoci, Pierluigi
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Van de Werf, Frans
    Armstrong, Paul W.
    Aylward, Philip E.
    White, Harvey D.
    Moliterno, David J.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Chen, Edmond
    Harrington, Robert A.
    Strony, John
    Mahaffey, Kenneth W.
    Efficacy and Safety of Vorapaxar in Elderly Patients With Non-ST-Segment Elevation Acute Coronary Syndrome: Insights From the TRACER Trial2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 22Article in journal (Other academic)
  • 7.
    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.

  • 8. Bagai, Akshay
    et al.
    Huang, Zhen
    Lokhnygina, Yuliya
    Harrington, Robert A.
    Armstrong, Paul W.
    Strony, John
    Chen, Edmond
    White, Harvey D.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Van de Werf, Frans
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Tricoci, Pierluigi
    Mahaffey, Kenneth W.
    Differential Prognostic Implications of Peak Troponin Level in Acute Coronary Syndrome Treated With and Without Revascularization2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 22Article in journal (Other academic)
  • 9. Bagai, Akshay
    et al.
    Huang, Zhen
    Lokhnygina, Yuliya
    Harrington, Robert A
    Armstrong, Paul W
    Strony, John
    White, Harvey D
    Leonardi, Sergio
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Van de Werf, Frans
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Tricoci, Pierluigi
    Mahaffey, Kenneth W
    Magnitude of troponin elevation and long-term clinical outcomes in acute coronary syndrome patients treated with and without revascularization.2015In: Circulation. Cardiovascular Interventions, ISSN 1941-7640, E-ISSN 1941-7632, Vol. 8, no 6, article id e002314Article in journal (Refereed)
    Abstract [en]

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

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

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

  • 10.
    Bahit, M. C.
    et al.
    INECO Neurociencias, Rosario, Santa Fe, Argentina..
    Lopes, R. D.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    Wojdyla, D. M.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hanna, M.
    Bristol Myers Squibb Co, Princeton, NJ USA..
    Vinereanu, D.
    Univ Med & Pharm Carol Davila, Bucharest, Romania..
    Goto, S.
    Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan..
    Alexander, J. H.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Granger, C. B.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    Less non-major bleeding with apixaban versus warfarin among patients with atrial fibrillation: insights from the ARISTOTLE trial2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no Suppl. 1, p. 338-339Article in journal (Other academic)
  • 11.
    Bahit, M. Cecilia
    et al.
    INECO, Neurociencias Orono Rosario, Santa Fe, NM, Argentina..
    Lopes, Renato D.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Wojdyla, Daniel M.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hanna, Michael
    Bristol Myers Squibb, Princeton, NJ USA..
    Vinereanu, Dragos
    Univ Med & Pharm Carol Davila, Bucharest, Romania..
    Hylek, Elaine M.
    Boston Univ, Med Ctr, Boston, MA USA..
    Verheugt, Freek
    Onze Lieve Vrouwe Gasthuis OLVG, Heartctr, Amsterdam, Netherlands..
    Goto, Shinya
    Tokai Univ, Sch Med, Isehara, Kanagawa, Japan..
    Alexander, John H.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Granger, Christopher B.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Non-major bleeding with apixaban versus warfarin in patients with atrial fibrillation2017In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 103, no 8, p. 623-628Article in journal (Refereed)
    Abstract [en]

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

  • 12.
    Batra, Gorav
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    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.
    Jernberg, Tomas
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Johanson, Per
    Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden.;AstraZeneca, Gothenburg, Sweden..
    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, 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.
    All types of atrial fibrillation in the setting of myocardial infarction are associated with impaired outcome2016In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 102, no 12, p. 926-933Article in journal (Refereed)
    Abstract [en]

    Objectives To evaluate 90-day cardiovascular outcome in patients after myocardial infarction (MI) in relation to different subtypes of atrial fibrillation (AF) and MI. Methods We studied 155 071 hospital survivors of MI between 2000 and 2009 in Swedish registries. AF subtypes were defined according to history of AF and in-hospital ECG recordings. Clinical outcomes were evaluated with multivariable Cox models. Results AF was documented in 24 023 (15.5%) cases. The AF subtypes were new-onset AF with sinus rhythm at discharge (3.7%), new-onset AF with AF at discharge (3.9%), paroxysmal AF (4.9%) and chronic AF (3.0%). The event rate per 100 person-years for the composite cardiovascular outcome (all-cause mortality, MI or ischaemic stroke) was 90.9 in patients with any type of AF versus 45.2 in patients with sinus rhythm, adjusted hazard ratio with 95% CI (HR) 1.28 (1.19 to 1.37). There were no significant differences in the composite cardiovascular outcome between AF subtypes. AF was associated with higher risk of mortality, HR 1.59 (1.41 to 1.80), reinfarction, HR 1.14 (1.05 to 1.24), and ischaemic stroke, HR 2.29 (1.92 to 2.74), respectively. In subgroup analysis, AF was associated with a higher risk of composite cardiovascular outcome in the non-ST-elevation myocardial infarction (NSTEMI) and STelevation myocardial infarction (STEMI) cohort, HR 1.24 (1.13 to 1.36) and HR 1.34 (1.21 to 1.48), respectively, with p value for interaction= 0.23. Conclusions AF is common in the setting of MI and is associated with a higher risk of composite cardiovascular outcome and the individual components; mortality, reinfarction and ischaemic stroke, respectively. No major difference in outcome was observed between AF subtypes. No difference in outcome for AF was observed between the NSTEMI and STEMI cohort.

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

    Aims

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

    Methods and results

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

    Conclusion

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

  • 14. Bennermo, Marie
    et al.
    Nordin, Margareta
    Lundman, Pia
    Boqvist, Susanna
    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.
    Samnegård, Ann
    Ericsson, Carl-Göran
    Silveira, Angela
    Hamsten, Anders
    Nastase, Maria Mannila
    Tornvall, Per
    Genetic and environmental influences on the plasma interleukin-6 concentration in patients with a recent myocardial infarction: a case-control study2011In: Journal of Interferon and Cytokine Research, ISSN 1079-9907, E-ISSN 1557-7465, Vol. 31, no 2, p. 259-264Article in journal (Refereed)
    Abstract [en]

    The aim was to study the stimuli responsible for triggering and sustaining the plasma concentration of the inflammatory marker interleukin-6 (IL-6) in patients with a first myocardial infarction before the age of 60 and healthy control subjects matched for age and sex. The plasma IL-6 concentration, antibodies against Chlamydia pneumoniae, cytomegalovirus, Epstein-Barr virus, Helicobacter pylori, herpes simplex type 1 and 2, and genotype for the IL6-174 G>C single-nucleotide polymorphism were determined 3 months after the acute event. The results showed that patients had higher IL-6 levels than control subjects, whereas there were no differences regarding individual or total number (pathogen burden) of positive antibody tests against the different pathogens or IL6 genotype distribution. The plasma IL-6 concentration was associated with the number of positive antibody tests in patients and control subjects, whereas patients irrespective of IL6 genotype had increased IL-6. Multivariate analysis, including traditional coronary heart disease risk factors, antibodies against pathogens, and IL6 genotype, explained 17% of the variation of the plasma IL-6 concentration. Neither pathogen burden nor IL6 genotype did contribute to the variation of plasma IL-6 levels, whereas smoking, body-mass index, hypertension, case-control status, and age were determinants of the plasma IL-6 concentration.

  • 15.
    Bhatt, Deepak L.
    et al.
    Harvard Med Sch, Brigham & Womens Hosp, Heart & Vasc Ctr, 75 Francis St, Boston, MA 02115 USA.
    Fox, Kim
    Imperial Coll, Natl Heart & Lung Inst, London, England;Royal Brompton Hosp, London, England.
    Harrington, Robert A.
    Stanford Univ, Dept Med, SCCR, Stanford, CA 94305 USA.
    Leiter, Lawrence A.
    Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada.
    Mehta, Shamir R.
    Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada;McMaster Univ, Hamilton, ON, Canada.
    Simon, Tabassome
    Sorbonne Univ Paris, Hop St Antoine, AP HP, Dept Clin Pharmacol URCEST, Paris, France.
    Andersson, Marielle
    AstraZeneca Gothenburg, Dept Cardiovasc Renal & Metab, Molndal, Sweden.
    Himmelmann, Anders
    AstraZeneca Gothenburg, Dept Cardiovasc Renal & Metab, Molndal, Sweden.
    Ridderstrale, Wilhelm
    AstraZeneca Gothenburg, Dept Cardiovasc Renal & Metab, Molndal, Sweden.
    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 Univ, Uppsala Clin Res Ctr, Dept Med Sci, Cardiol, Uppsala, Sweden.
    Steg, Philippe Gabriel
    Univ Paris Diderot, Hop Bichat, AP HP, Dept Hosp Univ FIRE,F CRIN Network,FACT, Paris, France;Univ Paris Diderot, Hop Bichat, AP HP, Dept Hosp Univ FIRE,INSERM,U 1148, Paris, France;Imperial Coll, Royal Brompton Hosp, NHLI, London, England.
    Steg, Gabriel
    Diaz, Rafael
    Amerena, John
    Huber, Kurt
    Sinnaeve, Peter
    Nicolau, Jose Carlos
    Kerr Saraiva, Jose Francisco
    Petrov, Ivo
    Corbalan, Ramon
    Ge, Junbo
    Zhao, Qiang
    Botero, Rodrigo
    Widimsky, Petr
    Kristensen, Steen Dalby
    Hartikainen, Juha
    Danchin, Nicolas
    Darius, Harald
    Fat, Tse Hung
    Kiss, Robert Gabor
    Pais, Prem
    Lev, Eli
    De Luca, Leonardo
    Goto, Shinya
    Ramos Lopez, Gabriel Arturo
    Cornel, Jan Hein
    Kontny, Frederic
    Medina, Felix
    Babilonia, Noe
    Opolski, Grzegorz
    Vinereanu, Dragos
    Zateyshchikov, Dmitry
    Ruda, Mikhail
    Elamin, Omer
    Kovar, Frantisek
    Dalby, Anthony John
    Jeong, Myung Ho
    Bueno, Hector
    James, Stefan
    Chiang, Chern-En
    Tresukosol, Damras
    Ongen, Zeki
    Ray, Kausik
    Parkhomenko, Alexander
    McGuire, Darren
    Kosiborod, Mikhail
    Nguyen, Tuan Quang
    Wallentin, Lars
    Fox, Keith A. A.
    Eikelboom, John W.
    Tuomilehto, Jaakko
    Lee, Kerry L.
    Al-Khalidi, Hussein R.
    Ellis, Stephen J.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Holmgren, Pernilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Heldestad, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hallberg, Theresa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Renlund Grausne, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alm, Cristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michelgård Palmquist, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Svanberg, Camilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Capell, Warren H.
    Nehler, Mark R.
    Hiatt, William R.
    Bonaca, Marc P.
    Houser, Stacey
    Bachler, Susie
    Jaeger, Nicole
    Aunes, Maria
    Brusehed, Asa
    Chen, Jersey
    Dahlof, Bjorn
    Dolezalova, Jitka
    Domzol, Maciej
    Findley, Magdalena
    Holmberg, Niclas
    Jahreskog, Marianne
    Knutsson, Mikael
    Kruszewski, Jakub
    Leonsson-Zachrisson, Maria
    Stark, Maj
    Winder, Elin
    Rationale, design and baseline characteristics of the effect of ticagrelor on health outcomes in diabetes mellitus patients Intervention study2019In: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 42, no 5, p. 498-505Article in journal (Refereed)
    Abstract [en]

    In the setting of prior myocardial infarction, the oral antiplatelet ticagrelor added to aspirin reduced the risk of recurrent ischemic events, especially, in those with diabetes mellitus. Patients with stable coronary disease and diabetes are also at elevated risk and might benefit from dual antiplatelet therapy. The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS, NCT01991795) is a Phase 3b randomized, double-blinded, placebo-controlled trial of ticagrelor vs placebo, on top of low dose aspirin. Patients >= 50 years with type 2 diabetes receiving anti-diabetic medications for at least 6 months with stable coronary artery disease as determined by a history of previous percutaneous coronary intervention, bypass grafting, or angiographic stenosis of >= 50% of at least one coronary artery were enrolled. Patients with known prior myocardial infarction (MI) or stroke were excluded. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety endpoint is Thrombolysis in Myocardial Infarction major bleeding. A total of 19 220 patients worldwide have been randomized and at least 1385 adjudicated primary efficacy endpoint events are expected to be available for analysis, with an expected average follow-up of 40 months (maximum 58 months). Most of the exposure is on a 60 mg twice daily dose, as the dose was lowered from 90 mg twice daily partway into the study. The results may revise the boundaries of efficacy for dual antiplatelet therapy and whether it has a role outside acute coronary syndromes, prior myocardial infarction, or percutaneous coronary intervention.

  • 16. Bjorkander, Inge
    et al.
    Forslund, Lennart
    Kahan, Thomas
    Ericson, Mats
    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.
    Rehnqvist, Nina
    Hjemdahl, Paul
    Differential Index: A Simple Time Domain Heart Rate Variability Analysis with Prognostic Implications in Stable Angina Pectoris2008In: Cardiology, ISSN 0008-6312, E-ISSN 1421-9751, Vol. 111, no 2, p. 126-133Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To examine the usefulness of time domain heart rate variability (HRV) measurements by a simple graphical method, the differential index (DI), in prognostic assessments of patients with chronic stable angina pectoris. METHODS: HRV measurements in the time domain by DI were compared to conventional measurements of standard deviation of all normal-to-normal intervals (SDNN), percent of differences between adjacent normal RR intervals >50 ms (PNN50) and square root of the mean of the sum of squares of differences between adjacent normal RR intervals (RMSSD) from 24-hour ambulatory electrocardiographic recordings in 678 patients in the Angina Prognosis Study in Stockholm. The patients received double-blind treatment with metoprolol or verapamil. Main outcome measures were cardiovascular death or non-fatal myocardial infarction during follow-up (median 40 months). RESULTS: Patients suffering cardiovascular death (n = 30) had lower DI, SDNN and PNN50 (all p < 0.001). In a multivariate Cox model, DI below median independently predicted cardiovascular death (p = 0.002), as did SDNN (p = 0.016) and PNN50 (p = 0.030), but not RMSSD (p = 0.10). The separation of survival curves was most pronounced and specificity was slightly better with DI. DI and PNN50 increased with metoprolol but not verapamil treatment. Short-term treatment effects were not related to prognosis. CONCLUSIONS: Low time domain HRV carries independent prognostic information regarding cardiovascular death in stable angina pectoris. The simple DI method provided equally good or better prognostic information than conventional, more laborious HRV methods.

  • 17.
    Bosch, Jackie
    et al.
    McMaster Univ, Sch Rehabil Sci, Populat Hlth Res Inst, Hamilton, ON, Canada;McMaster Univ, Sch Rehabil Sci, Hamilton Hlth Sci, Hamilton, ON, Canada.
    O'Donnell, Martin
    McMaster Univ, Sch Rehabil Sci, Populat Hlth Res Inst, Hamilton, ON, Canada;NUI Galway, Dept Med, Res Board Clin Res Facil, Galway, Ireland.
    Swaminathan, Balakumar
    McMaster Univ, Sch Rehabil Sci, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Lonn, Eva Marie
    McMaster Univ, Sch Rehabil Sci, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Sharma, Mikul
    McMaster Univ, Sch Rehabil Sci, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Dagenais, Gilles
    Univ Laval, Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ, Canada.
    Diaz, Rafael
    Inst Cardiovasc Rosario, Rosario, Santa Fe, Argentina.
    Khunti, Kamlesh
    Univ Leicester, Diabet Res Ctr, Leicester, Leics, England.
    Lewis, Basil S.
    Technion Israel Inst Technol, Ruth & Bruce Rappaport Sch Med, Lady Davis Carmel Med Ctr, Haifa, Israel.
    Avezum, Alvaro
    Dante Pazzanese Inst Cardiol, Sao Paulo, Brazil.
    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.
    Keltai, Matyas
    Semmelweis Univ, Budapest, Hungary.
    Reid, Christopher
    Monash Univ, Melbourne, Vic, Australia.
    Toff, William D.
    Univ Leicester, Glenfield Hosp, Leicester Cardiovasc Biomed Res Unit, Dept Cardiovasc Sci, Leicester, Leics, England;Univ Leicester, Glenfield Hosp, Leicester Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, Leicester, Leics, England.
    Dans, Antonio
    Univ Philippines, Coll Med, Manila, Philippines.
    Leiter, Lawrence A.
    Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada.
    Sliwa, Karen
    Univ Cape Town, Soweto Cardiovasc Res Grp, Dept Med, Hatter Inst Cardiovasc Res Africa, Rondebosch, South Africa.
    Lee, Shun Fu
    McMaster Univ, Sch Rehabil Sci, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Pogue, Janice M.
    McMaster Univ, Sch Rehabil Sci, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Hart, Robert
    McMaster Univ, Sch Rehabil Sci, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Yusuf, Salim
    McMaster Univ, Sch Rehabil Sci, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Effects of blood pressure and lipid lowering on cognition Results from the HOPE-3 study2019In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 92, no 13, p. E1435-E1446Article in journal (Refereed)
    Abstract [en]

    Objective: To assess whether long-term treatment with candesartan/hydrochlorothiazide, rosuvastatin, or their combination can slow cognitive decline in older people at intermediate cardiovascular risk.

    Methods: The Heart Outcomes Prevention Evaluation-3 (HOPE-3) study was a double-blind, randomized, placebo-controlled clinical trial using a 2 x 2 factorial design. Participants without known cardiovascular disease or need for treatment were randomized to candesartan (16 mg) plus hydrochlorothiazide (12.5 mg) or placebo and to rosuvastatin (10 mg) or placebo. Participants who were >= 70 years of age completed the Digit Symbol Substitution Test (DSST), the modified Montreal Cognitive Assessment, and the Trail Making Test Part B at baseline and study end.

    Results: Cognitive assessments were completed by 2,361 participants from 228 centers in 21 countries. Compared with placebo, candesartan/hydrochlorothiazide reduced systolic blood pressure by 6.0 mm Hg, and rosuvastatin reduced low-density lipoprotein cholesterol by 24.8 mg/dL. Participants were followed up for 5.7 years (median), and 1,626 completed both baseline and study-end assessments. Mean participant age was 74 years (SD +/- 3.5 years); 59% were women; 45% had hypertension; and 24% had >= 12 years of education. The mean difference in change in DSST scores was -0.91 (95% confidence interval [CI] -2.25 to 0.42) for candesartan/hydrochlorothiazide compared with placebo, -0.54 (95% CI -1.88 to 0.80) for rosuvastatin compared with placebo, and -1.43 (95% CI -3.37 to 0.50) for combination therapy vs double placebo. No significant differences were found for other measures.

    Conclusions: Long-term blood pressure lowering with candesartan plus hydrochlorothiazide, rosuvastatin, or their combination did not significantly affect cognitive decline in older people. ClinicalTrials.gov identifier: NCT00468923. Classification of evidence: This study provides Class II evidence that for older people, candesartan plus hydrochlorothiazide, rosuvastatin, or their combination does not significantly affect cognitive decline.

  • 18. Brilakis, Emmanouil
    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
    Cornel, Jan
    Aylward, Philip
    Lewis, Basil
    Weaver, Douglas
    Brandrup-Wognsen, Gunnar
    Stevens, Susanna
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, 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) trial2012In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 60, no 17, p. B215-B216Article in journal (Other academic)
  • 19. 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.

  • 20.
    Bui, An H.
    et al.
    Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med,Cardiovasc Div, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA..
    Cannon, Christopher P.
    Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med,Cardiovasc Div, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA..
    Steg, Philippe Gabriel
    INSERM Unite 1148, Paris, France.;Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, F-75877 Paris, France.;Univ Paris Diderot, Sorbonne Paris Cite, Dept Cardiol, Paris, France.;NHLI Imperial Coll, ICMS, Dept Cardiol, Royal Brompton Hosp, London, England..
    Storey, Robert F.
    Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England..
    Husted, Steen
    Hosp Unit West, Dept Med, Herning Holstebro, Denmark..
    Guo, Jianping
    Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med,Cardiovasc Div, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA..
    Im, KyungAh
    Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med,Cardiovasc Div, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 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.
    Michelson, Eric L.
    Thomas Jefferson Univ, Dept Med, Philadelphia, PA 19107 USA..
    Himmelmann, Anders
    AstraZeneca Res & Dev, Gothenburg, Sweden..
    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.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, 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.
    Scirica, Benjamin M.
    Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med,Cardiovasc Div, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA..
    Relationship Between Early and Late Nonsustained Ventricular Tachycardia and Cardiovascular Death in Patients With Acute Coronary Syndrome in the Platelet Inhibition and Patient Outcomes (PLATO) Trial2016In: Circulation: Arrhythmia and Electrophysiology, ISSN 1941-3149, E-ISSN 1941-3084, Vol. 9, no 2, article id e002951Article in journal (Refereed)
    Abstract [en]

    Background- Nonsustained ventricular tachycardia (NSVT) is common after acute coronary syndrome (ACS) and a marker of increased risk of arrhythmogenic death. However, the prognostic significance of NSVT when evaluated with other contemporary risk markers and at later time points after ACS remains uncertain. Methods and Results- In the Platelet Inhibition and Patient Outcomes (PLATO) trial, continuous ECGs were performed during the first 7 days after ACS (n=2866) and repeated for another 7 days at day 30 (n=1991). Median follow-up was 1 year. There was a time-varying interaction between NSVT and cardiovascular death such that NSVT was significantly associated with increased risk within the first 30 days after randomization (22/999 [2.2%] versus 16/1825 [0.9%]; adjusted hazard ratio, 2.84; 95% confidence interval, 1.39-5.79; P=0.004) but not after 30 days (28/929 [3.0%] versus 42/1734 [2.4%]; P=0.71). Detection of NSVT during the convalescent phase (n=428/1991; 21.5%) was also associated with an increased risk of cardiovascular death, and was most marked within the first 2 months after detection (1.9% versus 0.3%; adjusted hazard ratio, 5.48; 95% confidence interval, 1.07-28.20; P=0.01), and then decreasing over time such that the relationship was no longer significant by approximate to 5 months after ACS. Conclusions- NSVT occurred frequently during the acute and convalescent phases of ACS. The risk of cardiovascular death associated with NSVT was the greatest during the first 30 days after presentation; however, patients with NSVT detected during the convalescent phase were also at a significantly increased risk of cardiovascular death that persisted for an additional several months after the index event.

  • 21.
    Carrero, Juan J.
    et al.
    Karolinska Inst, Renal Med, Stockholm, Sweden..
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jensevik, Karin
    Szummer, Karolina
    Karolinska Inst, Cardiol, Stockholm, Sweden..
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden..
    Evans, Marie
    Karolinska Inst, Renal Med, Stockholm, Sweden..
    Spaak, Jonas
    Karolinska Inst, Clin Sci, Stockholm, Sweden..
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    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.
    Jernberg, Tomas
    Karolinska Inst, Cardiol, Stockholm, Sweden..
    Clinical Outcomes Associated With The Duration Of Dual Antiplatelet Therapy With Clopidogrel And Aspirin In Chronic Kidney Disease Patients With Acute Coronary Syndrome2016In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 31, p. 1441-1441Article in journal (Other academic)
  • 22.
    Carrero, Juan-Jesus
    et al.
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden..
    Varenhorst, Christoph
    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.
    Jensevik, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Szummer, Karolina
    Karolinska Inst, Div Cardiol, Stockholm, 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.
    Evans, Marie
    Karolinska Inst, Div Renal Med, Stockholm, Sweden..
    Spaak, Jonas
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    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.
    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.
    Jernberg, Tomas
    Karolinska Inst, Div Cardiol, Stockholm, Sweden..
    Long-term versus short-term dual antiplatelet therapy was similarly associated with a lower risk of death, stroke, or infarction in patients with acute coronary syndrome regardless of underlying kidney disease2017In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 91, no 1, p. 216-226Article in journal (Refereed)
    Abstract [en]

    Scarce and conflicting evidence exists on whether clopidogrel is effective and whether dual antiplatelet treatment (DAPT) is safe in patients with acute coronary syndrome and chronic kidney disease (CKD). To study this, we performed an observational, prospective, multicenter cohort study of 36,001 patients of the SWEDEHEART registry. The exposure was DAPT prolonged after 3 months versus DAPT stopped at 3 months in consecutive patients with acute coronary syndrome and known serum creatinine. DAPT duration with clopidogrel and aspirin was assessed by dispensed tablets. CKD stages were classified according to estimated glomerular filtration rate (eGFR). Study outcomes were 1) the composite of death, myocardial infarction, or ischemic stroke; 2) bleeding; or 3) the aggregate of these two outcomes within day 111 and 365 from discharge. A longer DAPT duration, as compared with 3-month DAPT, was associated with lower hazard ratios for outcome one in each CKD stratum (eGFR over 60, adjusted hazard ratio [95% confidence interval] 0.76 [0.67-0.85]; eGFR 60 and less, 0.84 [0.73-0.96], of which eGFR between 45 and 60, 0.85 [0.70-1.05], eGFR between 30 and 45, 0.78 [0.62-0.97]; eGFR 30 and less ml/min/1.73 m(2), 0.93 [0.70-1.24]. Bleeding (outcome 2) was in general more common in the longer DAPT group of each aforementioned CKD stratum. Aggregated outcome analysis (outcome 3) similarly favored longer DAPT in each stratum. There was no interaction between DAPT duration and CKD strata for any of the study outcomes. Thus, a prolonged as compared with three-month DAPT was similarly associated with a lower risk of death, stroke, or reinfarction regardless of underlying CKD.

  • 23. Cornel, Jan H.
    et al.
    Tricoci, Pierluigi
    Lokhnygina, Yuliya
    Moliterno, David J.
    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.
    Aylward, Philip E.
    Clare, Robert M.
    Chen, Edmond
    Leonardi, Sergio
    de Werf, Frans Van
    White, Harvey D.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Strony, John
    Mahaffey, Kenneth W.
    Harrington, Robert A.
    Glycoprotein IIb/IIIa Receptor Inhibitors in Combination With Vorapaxar, a Platelet Thrombin Receptor Antagonist, Among Patients With Non-ST-Segment Elevation Acute Coronary Syndromes (from the TRACER Trial)2015In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 115, no 10, p. 1325-1332Article in journal (Refereed)
    Abstract [en]

    We evaluated the interaction between protease-activated receptor-1 antagonist vorapaxar and concomitant glycoprotein (GP) IIb/IIIa receptor inhibitors in patients with non-ST-segment elevation acute coronary syndromes who underwent PCI. In Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome trial, 12,944 patients with non-ST-segment elevation acute coronary syndromes were randomized to vorapaxar or placebo. Administration of GP IIb/IIIa receptor inhibitors was allowed at the treating physician's discretion. We investigated whether use of GP IIb/IIIa receptor inhibitors modified vorapaxar's effect on non-coronary artery bypass grafting (CABG)-related bleeding at 7 days and ischemic events at 30 days. In total, 7,455 patients underwent PCI during index hospitalization. Of these, 2,023 patients (27.1%) received inhibitors and 5,432 (72.9%) did not. Vorapaxar was associated with a numerically higher rate of non-CABG-related moderate/severe Global Use of Strategies to Open Occluded Arteries (GUSTO) bleeding at 7 days compared with placebo in those who did (1.3% vs 1.0%) and did not (0.6% vs 0.4%) receive GP IIb/IIIa receptor inhibitors. Ischemic end point rates at 30 days were not significantly lower with vorapaxar versus placebo. Increased rates of non-CABG GUSTO moderate/severe bleeding were observed in patients who received GP IIb/IIIa receptor inhibitors versus those who did not (adjusted hazard ratio [HR] 1.77, 95% confidence interval [CI] 0.43 to 7.35 in placebo arm; adjusted HR 2.02, 95% CI 0.62 to 6.61 in vorapaxar arm) and in those who received vorapaxar versus placebo (adjusted HR 1.54, 95% CI 0.36 to 6.56 in the GP IIn/IIIa group; adjusted FIR 1.34, 95% CI 0.44 to 4.07 in the no-GP IIb/IIIa group). No interaction was found between vorapaxar and inhibitor use up to 7 days (P interaction = 0.89) nor at the end of the treatment (P interaction = 0.74); however, the event rate was low. Also, no interaction was observed for efficacy end points after PCI at 30 days or at the end of the treatment. In conclusion, GP IIb/IIIa receptor inhibitor use plus dual antiplatelet therapy in a population with non-ST-segment elevation myocardial infarction planned for PCI was frequent but did not interact with vorapaxar's efficacy or safety. Nonetheless, GP IIb/IIIa receptor inhibitors and vorapaxar were associated with increased bleeding risk, and their combined use may result in additive effects on bleeding rates.

  • 24.
    Dagenais, Gilles R.
    et al.
    Lava Univ, Quebec Heart & Lung Univ Inst, Quebec City, PQ, Canada.
    Jung, Hyejung
    McMaster Univ, Hamilton Gen Hosp, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Lonn, Eva
    McMaster Univ, Hamilton Gen Hosp, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Bogaty, Peter M.
    Lava Univ, Quebec Heart & Lung Univ Inst, Quebec City, PQ, Canada.
    Dehghan, Mahshid
    McMaster Univ, Hamilton Gen Hosp, Populat Hlth Res Inst, Hamilton, ON, Canada.
    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.
    Avezum, Alvaro
    Univ Santo Amaro, Dante Pazzanese Inst Cardiol, Sao Paulo, Brazil.
    Jansky, Petr
    Univ Hosp Motol, Prague, Czech Republic.
    Keltai, Matyas
    Semmelweis Univ, Budapest, Hungary.
    Leiter, Lawrence A.
    Univ Toronto, Li Ka Shing Knowledge Inst, St Michaels Hosp, Toronto, ON, Canada;Univ Toronto, Dept Med, Toronto, ON, Canada;Univ Toronto, Dept Nutr Sci, Toronto, ON, Canada.
    Lopez-Jaramillo, Patricio
    Univ Santander UDES, Med Sch, Res Dept, FOSCAL, Bucaramanga, Colombia.
    Toff, William D.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England;NIHR Leicester Biomed Res Ctr, Leicester, Leics, England.
    Bosch, Jackie
    McMaster Univ, Hamilton Gen Hosp, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Yusuf, Salim
    McMaster Univ, Hamilton Gen Hosp, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Effects of Lipid-Lowering and Antihypertensive Treatments in Addition to Healthy Lifestyles in Primary Prevention: An Analysis of the HOPE-3 Trial2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 15, article id e008918Article in journal (Refereed)
    Abstract [en]

    Background-It is not clear whether the effects of lipid-lowering or antihypertensive medications are influenced by adherence to healthy lifestyle factors. We assessed the effects of both drug interventions in subgroups by the number of healthy lifestyle factors in participants in the HOPE-3 (Heart Outcomes Prevention Evaluation) trial. Methods and Results-In this primary prevention trial, 4 healthy lifestyle factors (nonsmoking status, physical activity, optimal body weight, and healthy diet) were recorded in 12 521 participants who were at intermediate risk of cardiovascular disease (CVD) and were randomized to rosuvastatin, candesartan/hydrochlorothiazide, their combination, or matched placebos. Median follow-up was 5.6 years. The outcome was a composite of CVD events. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models. Participants with >= 2 healthy lifestyle factors had a lower rate of CVD compared with those with fewer factors (HR: 0.85; 95% CI, 0.73-1.00). Rosuvastatin reduced CVD events in participants with >= 2 healthy lifestyle factors (HR: 0.74; 95% CI, 0.62-0.90) and in participants with <2 factors (HR: 0.79; 95% CI, 0.61-1.01). Consistent results were observed with combination therapy (>= 2 factors: HR: 0.74; 95% CI, 0.57-0.97; <2 factors: HR: 0.61; 95% CI, 0.43-0.88). Candesartan/hydrochlorothiazide tends to reduce CVD only in participants with <2 healthy lifestyle factors (HR: 0.78; 95% CI, 0.61-1.00). Conclusions-Healthy lifestyles are associated with lower CVD. Rosuvastatin alone and combined with candesartan/hydrochlorothiazide is beneficial regardless of healthy lifestyle status; however, the benefit of antihypertensive treatment appears to be limited to patients with less healthy lifestyles.

  • 25. Damman, Peter
    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.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jeppsson, Anders
    Jernberg, Tomas
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Invasive Strategies And Outcomes For Non-ST-segment Elevation Acute Coronary Syndromes: A Twelve-year Experience From SWEDEHEART2012In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 60, no 17, p. B133-B133Article in journal (Other academic)
  • 26.
    Damman, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jernberg, Tomas
    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.
    de Winter, Robbert J
    Jeppsson, Anders
    Johanson, Per
    Held, Claes
    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.
    Invasive strategies and outcomes for non-ST-segment elevation acute coronary syndromes: a twelve-year experience from SWEDEHEART.2016In: EuroIntervention, ISSN 1774-024X, E-ISSN 1969-6213, Vol. 12, no 9, p. 1108-1116Article in journal (Refereed)
    Abstract [en]

    AIMS: Despite recommendations in recent guidelines for a routine invasive strategy for non-ST-segment elevation acute coronary syndrome (NSTE-ACS), long-term data on the implementation of treatment strategies in clinical practice are not available. Our aim was to provide long-term data on the implementation of a routine invasive strategy in NSTE-ACS in clinical practice.

    METHODS AND RESULTS: In the SWEDEHEART registry, data from 204,092 consecutive NSTE-ACS patients admitted between 1996 and 2007 were recorded. The use of the routine invasive strategy, retrospectively defined as coronary angiography (and subsequent revascularisation) within three days after admission, increased from 3.8% in the period 1996-1998 to 37.4% in the period 2005-2007. The largest absolute increase in the use of this strategy was observed in low-risk patients, while a similar relative increase was observed in all risk categories. The use of the selective invasive strategy, defined as coronary angiography later than three days after admission or none at all, decreased from 96.2% in the period 1996-1998 to 62.5% in the period 2005-2007. In the total population, there was a gradual decrease in three-year all-cause mortality, from 29.1% in the period 1996-1998 to 23.9% in the period 2005-2007.

    CONCLUSIONS: There has been an increase in the use of a routine invasive strategy in NSTE-ACS patients over the course of 12 years in Sweden. There was a decrease in three-year mortality over the same time course.

  • 27.
    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.

  • 28. Dery, Jean-Pierre P.
    et al.
    Mahaffey, Kenneth
    Tricoci, Pierluigi
    White, Harvey
    Podder, Mohua
    Moliterno, David
    Harrington, Robert
    Chen, Edmond
    Strony, John
    Van de Werf, Frans
    Ziada, Khaled M.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Aylward, Philip
    Armstrong, Paul W.
    Rao, Sunil
    Arterial Access Site and Outcomes in Patients Undergoing Percutaneous Coronary Intervention With and Without Vorapaxar2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 22Article in journal (Other academic)
  • 29.
    Ducrocq, G.
    et al.
    Hop Bichat Claude Bernard, AP HP, F-75877 Paris 18, France..
    Schulte, P. J.
    Duke Clin Res Inst, Durham, NC USA..
    Budaj, A.
    Grochowski Hosp, Warsaw, Poland..
    Cornel, J. H.
    Med Ctr Alkmaar, Alkmaar, Netherlands..
    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.
    Himmelmann, A.
    AstraZeneca Res & Dev, Molndal, Sweden..
    Husted, S.
    Holstebro Hosp, Holstebro, Denmark..
    Storey, R. F.
    Univ Sheffield, Sheffield, S Yorkshire, England..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Steg, P. G.
    Hop Bichat Claude Bernard, F-75877 Paris 18, France..
    Balancing the risk of ischaemic and bleeding events in ACS2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no Suppl. 1, p. 860-861Article in journal (Other academic)
  • 30. Ducrocq, G.
    et al.
    Schulte, P. J.
    Cannon, C. P.
    Becker, R. C.
    Harrington, R. A.
    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, A.
    Sorbets, E.
    Wallentin, L.
    Steg, P. G.
    Prognostic implications of major bleeding on mortality in ACS patients: An analysis of the PLATO trial2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, p. 724-724Article in journal (Refereed)
  • 31. Ducrocq, Gregory
    et al.
    Schulte, P J
    Becker, R C
    Cannon, C P
    Harrington, R A
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Himmelmann, A
    Lassila, R
    Storey, R F
    Sorbets, E
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Steg, P G
    Association of spontaneous and procedure-related bleeds with short- and long-term mortality after acute coronary syndromes:: an analysis from the PLATO trial2015In: EuroIntervention, ISSN 1774-024X, E-ISSN 1969-6213, Vol. 11, no 7, p. 737-745Article in journal (Refereed)
    Abstract [en]

    Aims: We sought to describe the differential effect of bleeding events in acute coronary syndromes (ACS) on short- and long-term mortality according to their type and severity.

    Methods and results: The PLATO trial randomised 18,624 ACS patients to clopidogrel or ticagrelor. Post-randomisation bleeding events were captured according to bleeding type (spontaneous or procedure-related), with PLATO, TIMI, and GUSTO definitions. The association of bleeding events with subsequent short-term (<30 days) and long-term (>30 days) all-cause mortality was assessed using time-dependent Cox proportional hazard models. A model was fitted to compare major and minor bleeding for mortality prediction. Of 18,624 patients, 2,189 (11.8%) had at least one PLATO major bleed (mean follow-up 272.2±123.5 days). Major bleeding was associated with higher short-term mortality (adjusted hazard ratio [HR] 9.28; 95% confidence interval [CI]: 7.50-11.48) but not with long-term mortality (adjusted HR 1.28; 95% CI: 0.93-1.75). Spontaneous bleeding was associated with short-term (adjusted HR 14.59; 95% CI: 11.14-19.11) and long-term (adjusted HR 3.38; 95% CI: 2.26-5.05) mortality. Procedure-related bleeding was associated with short-term mortality (adjusted HR 5.29; 95% CI: 4.06-6.87): CABG-related and non-coronary-procedure-related bleeding were associated with a higher short-term mortality, whereas PCI or angiography-related bleeding was not associated with either short- or long-term mortality. Similar results were obtained using the GUSTO and TIMI bleeding definitions.

    Conclusions: Major bleeding is associated with high subsequent mortality in ACS. However, this association is much stronger in the first 30 days and is strongest for spontaneous (vs. procedure-related) bleeding.

  • 32.
    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.

  • 33.
    Durheim, Michael T.
    et al.
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Durham, NC USA..
    Cyr, Derek D.
    Duke Clin Res Inst, Durham, NC USA..
    Lopes, Renato D.
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA..
    Thomas, Laine E.
    Duke Clin Res Inst, Durham, NC USA..
    Tsuang, Wayne M.
    Cleveland Clin, Dept Pulm Med, Cleveland, OH 44106 USA..
    Gersh, Bernard J.
    Coll Med, Mayo Clin, Div Cardiovasc Dis, Rochester, MN 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.
    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.
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA..
    Palmer, Scott M.
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Durham, NC USA..
    Al-Khatib, Sana M.
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA..
    Chronic obstructive pulmonary disease in patients with atrial fibrillation: Insights from the ARISTOTLE trial2016In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 202, p. 589-594Article in journal (Refereed)
    Abstract [en]

    Background: Comorbid chronic obstructive pulmonary disease (COPD) is associated with poor outcomes among patients with cardiovascular disease. The risks of stroke and mortality associated with COPD among patients with atrial fibrillation are not well understood. Methods: We analyzed patients from ARISTOTLE, a randomized trial of 18,201 patients with atrial fibrillation comparing the effects of apixaban versus warfarin on the risk of stroke or systemic embolism. Using Cox proportional hazards models, we assessed the associations between comorbid COPD and risk of stroke or systemic embolism and of mortality, adjusting for treatment allocation, smoking history and other risk factors. Results: COPD was present in 1950 (10.8%) of 18,134 patients with data on pulmonary disease history. After multivariable adjustment, COPD was not associated with risk of stroke or systemic embolism (adjusted HR 0.85 [95% CI 0.60, 1.21], p = 0.356). However, COPD was associated with a higher risk of all-cause mortality (adjusted HR 1.60 [95% CI 1.36, 1.88], p < 0.001) and both cardiovascular and non-cardiovascular mortality. The benefit of apixaban over warfarin on stroke or systemic embolism was consistent among patients with and without COPD (HR 0.92 [95% CI 0.52, 1.63] versus 0.78 [95% CI 0.65, 0.95], interaction p = 0.617). Conclusions: COPD was independently associated with increased risk of cardiovascular and non-cardiovascular mortality among patients with atrial fibrillation, but was not associated with risk of stroke or systemic embolism. The effect of apixaban on stroke or systemic embolism in COPD patients was consistent with its effect in the overall trial population.

  • 34. Déry, Jean-Pierre
    et al.
    Mahaffey, Kenneth W
    Tricoci, Pierluigi
    White, Harvey D
    Podder, Mohua
    Westerhout, Cynthia M
    Moliterno, David J
    Harrington, Robert A
    Chen, Edmond
    Strony, John
    Van de Werf, Frans
    Ziada, Khaled M
    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.
    Aylward, Philip E
    Armstrong, Paul W
    Rao, Sunil V
    Arterial access site and outcomes in patients undergoing percutaneous coronary intervention with and without vorapaxar2016In: Catheterization and cardiovascular interventions, ISSN 1522-1946, E-ISSN 1522-726X, Vol. 88, no 2, p. 163-173Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: We evaluated outcomes associated with transradial vs. transfemoral approaches and vorapaxar in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) in the TRACER trial.

    BACKGROUND: Vorapaxar reduces ischemic events but increases the risk of major bleeding.

    METHODS: We compared 30-day and 2-year major adverse cardiac events (MACE: cardiovascular death, myocardial infarction, stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization) and noncoronary artery bypass graft (CABG)-related bleedings in 2,192 transradial and 4,880 transfemoral patients undergoing PCI after adjusting for confounding variables, including propensity for transradial access.

    RESULTS: Overall, 30-day GUSTO moderate/severe and non-CABG TIMI major/minor bleeding occurred less frequently in transradial (0.9% vs. 2.0%, P = 0.001) vs. transfemoral (1.1% vs. 2.5%, P = 0.005) patients. A similar reduction was seen at 2 years (3.3% vs. 4.7%, P = 0.008; 3.3% vs. 4.9%, P < 0.001, respectively). Transradial was associated with an increased risk of ischemic events at 30 days (OR 1.38, 95% CI 1.11-1.72; P = 0.004), driven primarily by increased periprocedural myocardial infarctions. At 2 years, rates of MACE were comparable (HR 1.14, 95% CI 0.98-1.33; P = 0.096). Although bleeding rates were higher with vorapaxar in transfemoral vs. transradial patients, there was no significant treatment interaction. Also, the access site did not modulate the association between vorapaxar and MACE.

    CONCLUSIONS: Transradial access was associated with lower bleeding rates and similar long-term ischemic outcomes, suggesting transradial access is safer than transfemoral access among ACS patients receiving potent antiplatelet therapies. Because of the nonrandomized allocation of arterial access, these results should be considered exploratory. © 2015 Wiley Periodicals, Inc.

  • 35. Edström Plüss, Cathrine
    et al.
    Billing, Ewa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Held, Claes
    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.
    Henriksson, Peter
    Kiessling, Anna
    Rydell Karlsson, Monica
    Wallén, Håkan N.
    Long-term effects of an expanded cardiac rehabilitation programme after myocardial infarction or coronary artery bypass surgery: a five-year follow-up of a randomized controlled study2011In: Clinical Rehabilitation, ISSN 0269-2155, E-ISSN 1477-0873, Vol. 25, no 1, p. 79-87Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the long-term effect of expanded cardiac rehabilitation on a composite end-point, consisting of cardiovascular death, myocardial infarction or readmission for cardiovascular disease, in patients with coronary artery disease.Design: Single-centre prospective randomized controlled trial.Setting: University hospital.Subjects: Two hundred and twenty-four patients with acute myocardial infarction or undergoing coronary artery by-pass grafting.Intervention: Patients were randomized to expanded cardiac rehabilitation (a one-year stress management programme, increased physical training, staying at a 'patient hotel' for five days after the event, and cooking sessions), or to standard cardiac rehabilitation. MAIN MEASURES: Data on cardiovascular death, myocardial infarction, readmission for cardiovascular disease and days at hospital for cardiovascular reasons were obtained from national registries of the Swedish National Board of Health and Welfare.Results: The primary end-point occurred in 121 patients altogether (54%). The number of cardiovascular events were reduced in the expanded rehabilitation group compared with the standard cardiac rehabilitation (53 patients (47.7%) versus 68 patients (60.2%); hazard ratio 0.69; P = 0.049). This was mainly because of a reduction of myocardial infarctions in the expanded rehabilitation group. During the five years 12 patients (10.8%) versus 23 patients (20.3%); hazard ratio 0.47; P = 0.047 had a myocardial infarction. Days at hospital for cardiovascular reasons were significantly reduced in patients who received expanded cardiac rehabilitation (median 6 days) compared with standard cardiac rehabilitation (median 10 days; P = 0.02).Conclusion: Expanded cardiac rehabilitation after acute myocardial infarction or coronary artery bypass grafting reduces cardiovascular morbidity and days at hospital for cardiovascular reasons.

  • 36.
    Erlinge, D.
    et al.
    Lund Univ, Dept Cardiol Clin Sci, Lund, Sweden..
    Omerovic, E.
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Fröbert, O.
    Rebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden..
    Linder, R.
    Danderyd Hosp, Dept Cardiol, Danderyd, Sweden..
    Danielewicz, M.
    Karlstad Hosp, PCI Unit, Karlstad, Sweden..
    Hamid, M.
    Malarsjukhuset, Dept Cardiol, Eskilstuna, Sweden..
    Swahn, E.
    Linkoping Univ Hosp, Dept Cardiol, Linkoping, Sweden..
    Henareh, L.
    Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Wagner, H.
    Helsingborg Lasarett, Dept Cardiol, Helsingborg, Sweden..
    Hårdhammar, P.
    Halmstad Cty Hosp, Dept Cardiol, Halmstad, Sweden..
    Sjögren, I.
    Falun Cent Hosp, Dept Cardiol, Falun, Sweden..
    Stewart, J.
    Skaraborgs Hosp, Dept Cardiol, Skovde, Sweden..
    Grimfjärd, P.
    Vastmanlands Sjukhus, Dept Internal Med, Vasteras, Sweden..
    Jensen, J.
    Karolinska Inst, Capio St Gorans Hosp, Dept Cardiol, Stockholm, Sweden..
    Aasa, M.
    Sodersjukhuset AB, Dept Cardiol, Stockholm, Sweden..
    Robertsson, L.
    Sodra Alvsborgs Sjukhus, Dept Cardiol, Boras, Sweden..
    Lindroos, P.
    Karolinska Inst, Capio St Gorans Hosp, Dept Cardiol, Stockholm, Sweden..
    Haupt, J.
    Sunderby Sjukhus, Dept Cardiol, Lulea, Sweden..
    Wikström, H.
    Kristianstad Hosp, Dept Cardiol, Kristianstad, Sweden..
    Ulvenstam, A.
    Ostersund Hosp, Dept Cardiol, Ostersund, Sweden..
    Bhiladvala, P.
    Lund Univ, Dept Cardiol Clin Sci, Lund, Sweden..
    Lindvall, B.
    Sundsvall Hosp, Dept Cardiol, Sundsvall, Sweden..
    Lundin, A.
    Lund Univ, Dept Cardiol Clin Sci, Lund, Sweden..
    Tödt, T.
    Lund Univ, Dept Cardiol Clin Sci, Lund, Sweden..
    Ioanes, D.
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Råmunddal, T.
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Kellerth, T.
    Rebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden..
    Zagozdzon, L.
    Rebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden..
    Götberg, M.
    Lund Univ, Dept Cardiol Clin Sci, Lund, Sweden..
    Andersson, J.
    Umea Univ, Dept Cardiol, Umea, Sweden..
    Angerås, O.
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Östlund, Ollie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, 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.
    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.
    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.
    Schersten, F.
    Lund Univ, Dept Cardiol Clin Sci, Lund, Sweden..
    Eriksson, P.
    Umea Univ, Dept Cardiol, Umea, Sweden..
    Koul, S.
    Lund Univ, Dept Cardiol Clin Sci, Lund, Sweden..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bivalirudin versus Heparin Monotherapy in Myocardial Infarction2017In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 377, no 12, p. 1132-1142Article in journal (Refereed)
    Abstract [en]

    BACKGROUND The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y 12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors. METHODS In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y(12) inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial-artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow-up. RESULTS A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P = 0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P = 0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P = 0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P = 0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P = 0.76). CONCLUSIONS Among patients undergoing PCI for myocardial infarction, the rate of the composite of death from any cause, myocardial infarction, or major bleeding was not lower among those who received bivalirudin than among those who received heparin monotherapy. (Funded by the Swedish Heart-Lung Foundation and others;

  • 37.
    Fanaroff, Alexander C.
    et al.
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Clare, Robert
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Pieper, Karen S.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Mahaffey, Kenneth W.
    Stanford Univ, Sch Med, Stanford Ctr Clin Res, Stanford, CA 94305 USA.
    Melloni, Chiara
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Green, Jennifer B.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA;Duke Univ, Div Endocrinol, Sch Med, Durham, NC USA.
    Alexander, John H.
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Jones, W. Schuyler
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Harrison, Robert W.
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Mehta, RaJendra H.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Povsic, Thomas J.
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Moreira, Humberto G.
    Univ Sao Paulo, Heart Inst InCor, Med Sch, Sao Paulo, Brazil.
    Ai-Khatib, Sana M.
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Roe, Matthew T.
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Kong, David F.
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Mathews, Robin
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Tricoci, Pierluigi
    CSL Behring, King Of Prussia, PA USA.
    Holman, Rury R.
    Univ Oxford, Diabet Trials Unit, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    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.
    Califf, Robert M.
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA;Verily Life Sci, San Francisco, CA USA.
    Alexander, Karen P.
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Lopes, Renato D.
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Frequency, Regional Variation, and Predictors of Undetermined Cause of Death in Cardiometabolic Clinical Trials: A Pooled Analysis of 9259 Deaths in 9 Trials2019In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139, no 7, p. 863-873Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Modern cardiometabolic clinical trials often include cardiovascular death as a component of a composite primary outcome, requiring central adjudication by a clinical events committee to classify cause of death. However, sometimes the cause of death cannot be determined from available data. The US Food and Drug Administration has indicated that this circumstance should occur only rarely, but its prevalence has not been formally assessed. METHODS: Data from 9 global clinical trials (2009-2017) with long-term follow-up and blinded, centrally adjudicated cause of death were used to calculate the proportion of deaths attributed to cardiovascular, noncardiovascular, or undetermined causes by therapeutic area (diabetes mellitus/pre-diabetes mellitus, stable atherosclerosis, atrial fibrillation, and acute coronary syndrome), region of patient enrollment, and year of trial manuscript publication. Patient-and trial-level variables associated with undetermined cause of death were identified using a logistic model. RESULTS: Across 127 049 enrolled participants from 9 trials, there were 9259 centrally adjudicated deaths: 5012 (54.1%) attributable to cardiovascular causes, 2800 (30.2%) attributable to noncardiovascular causes, and 1447 (15.6%) attributable to undetermined causes. There was variability in the proportion of deaths ascribed to undetermined causes by trial therapeutic area, region of enrollment, and year of trial manuscript publication. On multivariable analysis, acute coronary syndrome or atrial fibrillation trial (versus atherosclerotic vascular disease or diabetes mellitus/pre-diabetes mellitus), longer time from enrollment to death, more recent trial manuscript publication year, enrollment in North America (versus Western Europe), female sex, and older age were associated with greater likelihood of death of undetermined cause. CONCLUSIONS: In 9 cardiometabolic clinical trials with long-term followup, approximately 16% of deaths had undetermined causes. This provides a baseline for quality assessment of clinical trials and informs operational efforts to potentially reduce the frequency of undetermined deaths in future clinical research.

  • 38. Garcia, David
    et al.
    Alexander, John H
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wojdyla, Daniel M
    Thomas, Laine
    Hanna, Michael
    Al-Khatib, Sana M
    Dorian, Paul
    Ansell, Jack
    Commerford, Patrick
    Flaker, Greg
    Lanas, Fernando
    Vinereanu, Dragos
    Xavier, Denis
    Hylek, Elaine M
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Verheugt, Freek W A
    Granger, Christopher B
    Lopes, Renato D
    Management and clinical outcomes in patients treated with apixaban versus warfarin undergoing procedures2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 25, p. 3692-3698Article in journal (Refereed)
    Abstract [en]

    Using data from ARISTOTLE, we describe the periprocedural management of anticoagulation and rates of subsequent clinical outcomes among patients chronically anticoagulated with warfarin or apixaban. We recorded whether (and for how long) anticoagulant therapy was interrupted pre-procedure; whether bridging therapy was used; and the proportion of patients who experienced important clinical outcomes during the 30 days post-procedure. Of 10,674 procedures performed during follow-up in 5924 patients, 9260 were included in this analysis. Anticoagulant treatment was not interrupted pre-procedure 37.5% of the time. During the 30 days post-procedure, stroke or systemic embolism occurred after 16/4624 (0.35%) procedures among apixaban-treated patients and 26/4530 (0.57%) procedures among warfarin-treated patients (OR 0.601; 95% CI 0.322–1.120). Major bleeding occurred in 74/4560 (1.62%) procedures in the apixaban arm and 86/4454 (1.93%) in the warfarin arm (OR 0.846; 95% CI 0.614–1.166). The risk of death was similar with apixaban (54/4624 [1.17%]) and warfarin (49/4530 [1.08%]) (OR 1.082; 95% CI 0.733–1.598). Among patients in ARISTOTLE, the 30-day post-procedure stroke, death, and major bleeding rates were low and similar in apixaban- and warfarin-treated patients, regardless of whether anticoagulation was stopped beforehand. Our findings suggest that many patients on chronic anticoagulation can safely undergo procedures; some will not require a pre-procedure interruption of anticoagulation. ARISTOTLE ClinicalTrials.gov number (NCT00412984).

  • 39.
    Grönqvist, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Olsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Johansson, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Sjöström, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Informatics and Media. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Lindahl Norberg, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare. Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden..
    Hovén, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Sanderman, Robbert
    Department of Health Psychology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; Department of Psychology, Health and Technology, University of Twente, Enschede, Netherlands..
    van Achterberg, Theo
    Academic Centre for Nursing and Midwifery, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium.
    von Essen, Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Fifteen Challenges in Establishing a Multidisciplinary Research Program on eHealth Research in a University Setting: A Case Study2017In: Journal of Medical Internet Research, ISSN 1438-8871, E-ISSN 1438-8871, Vol. 19, no 5, article id e173Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    U-CARE is a multidisciplinary eHealth research program that involves the disciplines of caring science, clinical psychology, health economics, information systems, and medical science. It was set up from scratch in a university setting in 2010, funded by a governmental initiative. While establishing the research program, many challenges were faced. Systematic documentation of experiences from establishing new research environments is scarce.

    OBJECTIVE:

    The aim of this paper was to describe the challenges of establishing a publicly funded multidisciplinary eHealth research environment.

    METHODS:

    Researchers involved in developing the research program U-CARE identified challenges in the formal documentation and by reflecting on their experience of developing the program. The authors discussed the content and organization of challenges into themes until consensus was reached.

    RESULTS:

    The authors identified 15 major challenges, some general to establishing a new research environment and some specific for multidisciplinary eHealth programs. The challenges were organized into 6 themes: Organization, Communication, Implementation, Legislation, Software development, and Multidisciplinarity.

    CONCLUSIONS:

    Several challenges were faced during the development of the program and several accomplishments were made. By sharing our experience, we hope to help other research groups embarking on a similar journey to be prepared for some of the challenges they are likely to face on their way.

  • 40.
    Grönqvist, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Olsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Norlund, Fredrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Wallin, Emma
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Burell, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Hursti, Timo
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    von Essen, Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    U-CARE Heart: A Randomized Controlled Study of the Effects of Internet-based Cognitive Behavior Therapy on Depression and Anxiety in Patients with a Previous Myocardial Infarction: A Clinical Trial Protocol2013Conference paper (Refereed)
  • 41.
    Guimaraes, P. Oliveira
    et al.
    Duke Clin Res Inst, Durham, NC USA.
    Granger, C. B.
    Duke Clin Res Inst, Durham, NC USA.
    Chiswell, K.
    Duke Clin Res Inst, Durham, NC USA.
    Stebbins, A.
    Duke Clin Res Inst, Durham, NC USA.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hochman, J. S.
    NYU, Langone Med Ctr, New York, NY USA.
    Krug-Gourley, S.
    GlaxoSmithKline, King Of Prussia, PA USA.
    Lonn, E.
    McMaster Univ, Hamilton, ON, Canada.
    Lopes, R. L.
    Duke Clin Res Inst, Durham, NC USA.
    Stewart, R. A. H.
    Auckland City Hosp, Auckland, New Zealand.
    Vinereanu, D.
    Univ Med & Pharm Carol Davila, Bucharest, Romania.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    White, H. D.
    Auckland City Hosp, Auckland, New Zealand.
    Danchin, N.
    Univ Paris 05, Hop Europeen Georges Pompidou, Paris, France.
    Women with stable coronary artery disease have better clinical outcomes than men, but this association is modified by degree of depression: insights from the STABILITY trial2017In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 38, p. 188-188Article in journal (Other academic)
  • 42.
    Guimaraes, Patricia Oliveira
    et al.
    Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA..
    Granger, Christopher B.
    Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA.;Duke Univ, Med Ctr, Durham, NC USA..
    Stebbins, Amanda
    Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA..
    Chiswell, Karen
    Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 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.
    Hochman, Judith S.
    NYU, Dept Med, Langone Med Ctr, 550 1St Ave, New York, NY 10016 USA..
    Krug-Gourley, Susan
    GlaxoSmithKline, Metab Pathways & Cardiovasc Therapeut Area, Collegeville, PA USA..
    Lonn, Eva
    McMaster Univ, Dept Med, Hamilton, ON, Canada.;McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Lopes, Renato D.
    Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA.;Duke Univ, Med Ctr, Durham, NC USA..
    Stewart, Ralph A. H.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland, New Zealand..
    Vinereanu, Dragos
    Univ Med & Pharm Carol Davila, Bucharest, Romania..
    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.
    White, Harvey D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland, New Zealand..
    Hagström, Emil
    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.
    Danchin, Nicolas
    Hop Europeen Georges Pompidou, AP HP, INSERM U970, Paris, France.;Univ Paris 05, Paris, France..
    Sex Differences in Clinical Characteristics, Psychosocial Factors, and Outcomes Among Patients With Stable Coronary Heart Disease: Insights from the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) Trial2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 9, article id e006695Article in journal (Refereed)
    Abstract [en]

    Background-Greater understanding of differences between men and women with coronary heart disease is needed. Methods and Results-In this post hoc analysis of the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial, we described psychosocial factors, treatments, and outcomes of men versus women with stable coronary heart disease and explored the association of sex with psychosocial characteristics and cardiovascular risk. Cox proportional hazards models were used to assess the relationship between sex and outcomes. Interactions among sex, psychosocial factors, and the composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke were tested. Of 15 828 patients, 2967 (19%) were women. Among women, 21.2% felt often or always stressed at home (versus 9.8% of men), and 19.2% felt often or always sad or depressed (versus 10.1% of men; all P<0.0001). The median duration of follow-up was 3.7 years (25th-75th percentiles: 3.5-3.8 years). Use of evidence-based medications for coronary heart disease at baseline and 24 months was similar between sexes, as were event rates for all outcomes analyzed. In the multivariable model including psychosocial measures, female sex was associated with lower cardiovascular risk. There was a statistically significant interaction (P=0.03) such that the lower risk in women varied by depressive symptom frequency, whereby women who were more depressed had a risk similar to men. Conclusions-Female sex was independently associated with better long-term clinical outcomes, although this was modified by frequency of depressive symptoms. This suggests that emotional state may be an important target for improving outcomes in patients with coronary heart disease, specifically in women.

  • 43. 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.

  • 44.
    Hagström, Emil
    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.
    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.
    Response to Letter: 'Sorrow and cardiovascular events'2018In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 4, p. 415-415Article in journal (Other academic)
  • 45.
    Hagström, Emil
    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.
    Held, Claes
    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.
    Stewart, Ralph A H
    Aylward, Philip E
    Budaj, Andrzej
    Cannon, Christopher P
    Koenig, Wolfgang
    Krug-Gourley, Sue
    Mohler, Emile R
    Steg, Philippe Gabriel
    Tarka, Elizabeth
    Östlund, Ollie
    White, Harvey D
    Siegbahn, A
    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.
    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.
    Growth Differentiation Factor 15 Predicts All-Cause Morbidity and Mortality in Stable Coronary Heart Disease2017In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 63, no 1, p. 325-333Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Higher growth differentiation factor 15 (GDF-15) concentrations are associated with cardiovascular (CV) and non-CV morbidity and mortality. However, information on associations between GDF-15 and the risk of specific CV and non-CV events in stable coronary heart disease (CHD) patients is limited.

    METHODS: In 14 577 patients with stable CHD participating in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial (STABILITY), GDF-15 and other prognostic biomarkers (N-terminal pro-B-type natriuretic peptide, high-sensitivity troponin T, cystatin C, and high-sensitivity C-reactive protein) were measured. In adjusted Cox regression models, the associations between GDF-15 and the composite CV end point [CV death, myocardial infarction (MI), and stroke], as well as other CV and non-CV events, were assessed.

    RESULTS: The median concentration (interquartile range) of GDF-15 at baseline was 1253 (915-1827) ng/L. The hazard ratio for the composite end point for the highest compared to the lowest quartile of GDF-15 was 1.8 (95% CI, 1.5-2.2); for CV death, 2.63 (1.9-3.6); for sudden death, 3.06 (1.9-4.8); for heart failure (HF) death, 4.3 (1.3-14); for cancer death, 2.5 (1.3-4.7); for hospitalization for HF, 5.8 (3.2-10); for MI 1.4 (95% CI, 1.1-1.9); and for stroke, 1.8 (95% CI, 1.1-2.8). After adjustment for other prognostic biomarkers, GDF-15 remained significantly associated with all outcomes except for MI.

    CONCLUSIONS: In stable CHD, GDF-15 was independently associated with CV, non-CV, and cancer mortality, as well as with MI and stroke. When also adjusting for other prognostic biomarkers, the associations to all fatal and nonfatal events were maintained except for MI. Information on GDF-15, therefore, might be helpful when assessing the risk of adverse outcomes in patients with stable CHD. ClinicalTrials.gov Identifier: NCT00799903.

  • 46.
    Hagström, Emil
    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 Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Larsson, Tobias E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ingelsson, Erik
    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.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    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.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Plasma parathyroid hormone and the risk of cardiovascular mortality in the community2009In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 119, no 21, p. 2765-2771Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Diseases with elevated levels of parathyroid hormone (PTH) such as primary and secondary hyperparathyroidism are associated with increased incidence of cardiovascular disease and death. However, data on the prospective association between circulating PTH levels and cardiovascular mortality in the community are lacking. METHODS AND RESULTS: The Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men (mean age, 71 years; n=958), was used to investigate the association between plasma PTH and cardiovascular mortality. During follow-up (median, 9.7 years), 117 participants died of cardiovascular causes. In Cox proportional-hazards models adjusted for established cardiovascular risk factors (age, systolic blood pressure, diabetes, smoking, body mass index, total cholesterol, high-density lipoprotein cholesterol, antihypertensive treatment, lipid-lowering treatment, and history of cardiovascular disease), higher plasma PTH was associated with higher risk for cardiovascular mortality (hazard ratio for 1-SD increase in PTH, 1.38; 95% confidence interval, 1.18 to 1.60; P<0.001). This association remained essentially unaltered in participants without previous cardiovascular disease and in participants with normal PTH (<6.8 pmol/L) with no other signs of a disturbed mineral metabolism (normal serum calcium, 2.2 to 2.6 mmol/L; normal glomerular filtration rate, >50 mL . min(-1) . 1.73 m(-2) and without vitamin D deficiency, plasma 25-OH vitamin D >37.5 nmol/L). Interestingly, elevated plasma PTH (>5.27 pmol/L) accounted for 20% (95% confidence interval, 10 to 26) of the population-attributable risk proportion for cardiovascular mortality. CONCLUSIONS: Plasma PTH levels predict cardiovascular mortality in the community, even in individuals with PTH within the normal range. Further studies are warranted to evaluate the clinical implications of measuring PTH in cardiovascular risk prediction and to elucidate whether PTH is a modifiable risk factor.

  • 47.
    Hagström, Emil
    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 Surgical Sciences, Endocrine Surgery.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Larsson, Tobias E.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    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.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Plasma parathyroid hormone and risk of congestive heart failure in the community2010In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 12, no 11, p. 1186-1192Article in journal (Refereed)
    Abstract [en]

    In experimental studies parathyroid hormone (PTH) has been associated with underlying causes of heart failure (HF) such as atherosclerosis, left ventricular hypertrophy, and myocardial fibrosis. Individuals with increased levels of PTH, such as primary or secondary hyperparathyroidism patients, have increased risk of ischaemic heart disease and HF. Moreover, increasing PTH is associated with worse prognosis in patients with overt HF. However, the association between PTH and the development HF in the community has not been reported. In a prospective, community-based study of 864 elderly men without HF or valvular disease at baseline (mean age 71 years, the ULSAM study) the association between plasma (P)-PTH and HF hospitalization was investigated adjusted for established HF risk factors (myocardial infarction, hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, and hypercholesterolaemia) and variables reflecting mineral metabolism (S-calcium, S-phosphate, P-vitamin D, S-albumin, dietary calcium and vitamin D intake, physical activity, glomerular filtration rate, and blood draw season). During follow-up (median 8 years), 75 individuals were hospitalized due to HF. In multivariable Cox-regression analyses, higher P-PTH was associated with increased HF hospitalization (hazard ratio for 1-SD increase of PTH, 1.41, 95% CI 1.12-1.77, P = 0.003). Parathyroid hormone also predicted hospitalization in participants without apparent ischaemic HF and in participants with normal P-PTH. In a large community-based sample of elderly men, PTH predicted HF hospitalizations, also after accounting for established risk factors and mineral metabolism variables. Our data suggest a role for PTH in the development of HF even in the absence of overt hyperparathyroidism.

  • 48.
    Hagström, Emil
    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.
    Norlund, Fredrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Stebbins, Amanda
    Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA..
    Armstrong, P W
    University of Alberta, Edmonton, Canada..
    Chiswell, K
    Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA..
    Granger, C B
    Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA..
    López-Sendón, J
    Hospital Universitario La Paz, Instituto de investigacion IdiPaz, Paseo de la Castellana, Madrid, Spain..
    Pella, D
    Department of Medicine, PJ Safarik University, Kosice, Slovakia..
    Soffer, J
    Metabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline, Collegeville, PA, USA..
    Sy, R
    Department of Internal Medicine, College of Medicine, University of the Philippines-Manila, Manila, Philippines..
    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.
    White, H D
    Green Lane Cardiovascular Service, Auckland, New Zealand.; University of Auckland, Auckland, New Zealand..
    Stewart, R A H
    Green Lane Cardiovascular Service, Auckland, New Zealand.; University of Auckland, Auckland, New Zealand..
    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.
    Psychosocial stress and major cardiovascular events in patients with stable coronary heart disease2018In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 1, p. 83-92Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Assess the risk of ischaemic events associated with psychosocial stress in patients with stable coronary heart disease (CHD).

    METHODS: Psychosocial stress was assessed by a questionnaire in 14 577 patients (median age 65.0, IQR 59, 71; 81.6% males) with stable CHD on optimal secondary preventive therapy in the prospective randomized STABILITY clinical trial. Adjusted Cox regression models were used to assess associations between individual stressors, baseline cardiovascular risk factors and outcomes.

    RESULTS: After 3.7 years of follow-up, depressive symptoms, loss of interest and financial stress were associated with increased risk (hazard ratio, 95% confidence interval) of CV death (1.21, 1.09-1.34; 1.15, 1.05-1.27; and 1.19, 1.08-1.30, respectively) and the primary composite end-point of CV death, nonfatal MI or nonfatal stroke (1.21, 1.13-1.30; 1.19, 1.11-1.27; and 1.17, 1.10-1.24, respectively). Living alone was related to higher risk of CV death (1.68, 1.38-2.05) and the primary composite end-point (1.28, 1.11-1.48), whereas being married as compared with being widowed, was associated with lower risk of CV death (0.64, 0.49-0.82) and the primary composite end-point (0.81, 0.67-0.97).

    CONCLUSIONS: Psychosocial stress, such as depressive symptoms, loss of interest, living alone and financial stress, were associated with increased CV mortality in patients with stable CHD despite optimal medical secondary prevention treatment. Secondary prevention of CHD should therefore focus also on psychosocial issues both in clinical management and in future clinical trials.

  • 49. Halvorsen, Sigrun
    et al.
    Atar, Dan
    Yang, Hongqiu
    De Caterina, Raffaele
    Erol, Cetin
    Garcia, David
    Granger, Christopher B.
    Hanna, Michael
    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.
    Husted, Steen
    Hylek, Elaine M.
    Jansky, Petr
    Lopes, Renato D.
    Ruzyllo, Witold
    Thomas, Laine
    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.
    Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, no 28, p. 1864-1872Article in journal (Refereed)
    Abstract [en]

    Aims The risk of stroke in patients with atrial fibrillation (AF) increases with age. In the ARISTOTLE trial, apixaban when compared with warfarin reduced the rate of stroke, death, and bleeding. We evaluated these outcomes in relation to patient age. Methods and results A total of 18 201 patients with AF and a raised risk of stroke were randomized to warfarin or apixaban 5 mg b.d. with dose reduction to 2.5 mg b.d. or placebo in 831 patients with >= 2 of the following criteria: age >= 80 years, body weight <= 60 kg, or creatinine >= 133 mu mol/L. We used Cox models to compare outcomes in relation to patient age during 1.8 years median follow-up. Of the trial population, 30% were <65 years, 39% were 65 to <75, and 31% were >= 75 years. The rates of stroke, all-cause death, and major bleeding were higher in the older age groups (P < 0.001 for all). Apixaban was more effective than warfarin in preventing stroke and reducing mortality across all age groups, and associated with less major bleeding, less total bleeding, and less intracranial haemorrhage regardless of age (P interaction >0.11 for all). Results were also consistent for the 13% of patients >= 80 years. No significant interaction with apixaban dose was found with respect to treatment effect on major outcomes. Conclusion The benefits of apixaban vs. warfarin were consistent in patients with AF regardless of age. Owing to the higher risk at older age, the absolute benefits of apixaban were greater in the elderly.

  • 50.
    Hambraeus, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, 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.
    Johansson, Per
    Svennberg, Lars
    Cider, Asa
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    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.
    Friberg, Orjan
    Nilsson, Johan
    From-Attebring, Mona
    Harnek, Jan
    Jernberg, Tomas
    SWEDEHEART Annual Report 20122014In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 48, no S63, p. 1-Article in journal (Refereed)
    Abstract [en]

    The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) supports continuous monitoring and improvement of care for coronary artery disease, catheter-based and surgical coronary interventions, secondary prevention as well as catheter based and surgical valve intervention, by providing extensive data on base-line, diagnostic, procedural and outcome variables. Design. This national quality registry collects information from all Swedish hospitals treating patients with acute coronary artery disease and all patients undergoing coronary angiography, catheter-based interventions or heart surgery. Combination with other national mandatory official registries enables complete follow-up of all individuals regarding myocardial infarction, new interventional procedures, death and all-cause hospitalizations. The registry is governed by an independent steering committee and funded by the Swedish National Health care provider. The software is developed by Uppsala Clinical Research Center. Results. The SWEDEHEART Quality Index reflects overall quality of care for coronary artery disease including secondary prevention. In comparison with 2011, an improvement of the index occurred in 2012 overall. There was however, still a wide range in performance between individual centers, emphasizing the need for continuous monitoring of quality of care at a national as well as on a center level.

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