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  • 1.
    Arefalk, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Andersen, Kasper
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Smokeless Tobacco (Snus) and Outcome of Myocardial Infarction: a SWEDEHEART StudyManuscript (preprint) (Other academic)
    Abstract [en]

    Background

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

    Methods

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

    Results

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

    Conclusions

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

  • 2. Braun, Oscar O.
    et al.
    Angiolillo, Dominick J.
    Ferreiro, Jose L.
    Jakubowski, Joseph A.
    Winters, Kenneth J.
    Effron, Mark B.
    Duvvuru, Suman
    Costigan, Timothy M.
    Sundseth, Scott S.
    Walker, Joseph R.
    Saucedo, Jorge F.
    Kleiman, Neal S.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Enhanced active metabolite generation and platelet inhibition with prasugrel compared to clopidogrel regardless of genotype in thienopyridine metabolic pathways2013In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 110, no 6, p. 1223-1231Article in journal (Refereed)
    Abstract [en]

    Clopidogrel response varies according to the presence of genetic polymorphisms. The CYP2C19*2 allele has been associated with impaired response; conflicting results have been reported for CYP2C19*17, ABCB1, and PON1 genotypes. We assessed the impact of CYP2C19, PON1, and ABCB1 polymorphisms on clopidogrel and prasugrel pharmacodynamic (PD) and pharmacokinetic (PK) parameters. Aspirin-treated patients (N=194) with coronary artery disease from two independent, prospective, randomised, multi-centre studies comparing clopidogrel (75 mg) and prasugrel (10 mg) were genotyped and classified by predicted CYP2C19 metaboliser phenotype (ultra metabolisers [UM] = *17 carriers; extensive metabolisers [EM] = *1/1 homozygotes; reduced metabolisers [RM] = *2 carriers). ABCB1 T/T and C/T polymorphisms and PON1 A/A, A/G and G/G polymorphisms were also genotyped. PD parameters were assessed using VerifyNow (R) P2Y12 and vasodilator stimulated phosphoprotein (VASP) expressed as platelet reactivity index (PR!) after 14 days of maintenance dosing. Clopi-, dogrel and prasugrel active metabolite (AM) exposure was calculated in a cohort of 96 patients. For clopidogrel, genetic variants in CYP2C19, but notABCB1 or PON1, affected PK and PD. For prasugrel, none of the measured genetic variants affected PK or PD. Compared with clopidogrel, platelet inhibition with prasugrel was greater even in the CYP2C19 UM phenotype. Prasugrel generated more AM and achieved greater platelet inhibition than clopidogrel irrespective of CYP2C19, ABCB1, and PON1 polymorphisms. The lack of effect from genetic variants on prasugrel AM generation or antiplatelet activity is consistent with previous studies in healthy volunteers and is consistent with improved efficacy in acute coronary syndrome patients managed with percutaneous coronary intervention.

  • 3. Braun, Oscar O.
    et al.
    Johnell, Matilda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Brandt, John T.
    Jakubowski, Joseph A.
    Winters, Kenneth J.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Erlinge, David
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Greater reduction of platelet activation markers and platelet-monocyte aggregates by prasugrel compared to clopidogrel in stable coronary artery disease2008In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 100, no 4, p. 626-633Article in journal (Refereed)
    Abstract [en]

    Prasugrel, a novel P2Y(12) ADP-receptor antagonist, has been reported to achieve greater inhibition of platelet aggregation compared to clopidogrel as assessed by light transmission aggregometry. It was the objective of this study to investigate the effect of prasugrel on alternative markers of platelet activation in comparison to a high loading dose and the approved maintenance dose of clopidogrel. One hundred ten aspirin-treated patients with stable coronary artery disease were randomized to a loading dose (LD, day 1)/ maintenance dose (MD, days 2-29) of prasugrel 60 mg/10 mg or clopidogrel 600 mg/75 mg. Platelet activation markers were analyzed by whole blood flow cytometry pre-dose and at 2 and 24 hours after LD and pre-dose at 14 and 29 days. After stimulation with 20 muM ADP, 2 hours after LD, significantly lower expression of activated GPIIb/IIIa (4.3 vs. 21.8 [mean fluorescent intensity (MFI)], p < 0.001) and P-selectin (2.0 vs. 11.7 MFI, p < 0.001) along with decreased formation of platelet-monocyte aggregates (16.4% vs. 29.6% positive cells, p < 0.001) was observed with prasugrel versus clopidogrel. All these effects were maintained through 24 hours and during the MD period. In conclusion, prasugrel 60 mg LD and 10 mg MD inhibit several markers of platelet activation and the formation of platelet-monocyte aggregates more effectively than a 600 mg LD and 75 mg MD of clopidogrel. Attenuated platelet aggregation and reduced expression of platelet pro-coagulant and pro-inflammatory markers with prasugrel suggest the potential to reduce cardiovascular events both in the acute setting and in long-term treatment.

  • 4.
    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.

  • 5.
    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)
  • 6.
    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.

  • 7.
    Chen, Yundai
    et al.
    Chinese PLA Gen Hosp 301 Hosp, Dept Cardiol, Beijing, Peoples R China..
    Li, Dandan
    Chinese PLA Gen Hosp 301 Hosp, Dept Hematol, Beijing, Peoples R China..
    Jing, Jing
    Chinese PLA Gen Hosp 301 Hosp, Dept Hematol, Beijing, Peoples R China..
    Yan, Hongbing
    Natl Ctr Cardiovasc Dis, Cardiovasc Inst, Beijing, Peoples R China.;FuWai Hosp, Beijing, Peoples R China..
    Liu, Jinghua
    Capital Med Univ, Beijing Anzhen Hosp, Dept Cardiol, Beijing, Peoples R China..
    Shen, Zhujun
    Beijing Union Med Coll Hosp, Dept Cardiol, Beijing, Peoples R China..
    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.
    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.
    Treatment Trends, Effectiveness, and Safety of Statins on Lipid Goal Attainment in Chinese Percutaneous Coronary Intervention Patients: a Multicenter, Retrospective Cohort Study2017In: Clinical Therapeutics, ISSN 0149-2918, E-ISSN 1879-114X, Vol. 39, no 9, p. 1827-1839Article in journal (Refereed)
    Abstract [en]

    Purpose: Limited data exist on the use of statins in Chinese patients with coronary artery disease (CAD) treated with percutaneous coronary intervention (PCI). We therefore conducted this study to observe the usage trend and the effectiveness of statins on LDL-C goal attainment and other lipid parameters among PCI-treated patients.

    Methods: This multicenter, retrospective, observational, longitudinal cohort study was conducted in PCI-treated patients with CAD between July 1, 2011, and February 28, 2015. Primary study outcomes included statin treatment pattern after PCI and proportion of patients achieving target (LDL-C) levels 1 month after PCI and initiating statin therapy.

    Findings: Data were analyzed for 2708 patients (mean age, 59 [10] years; median body mass index, 25.6 [4.0] kg/m(2)). From baseline to the end of 1 month, atorvastatin and rosuvastatin were the most prescribed statins; 20 mg and 10 mg were the most prescribed doses and therefore chosen for efficacy comparisons. In patients without dose changes, LDL-C reduction with rosuvastatin 10 mg was significantly greater compared with atorvastatin 20 mg (-0.67 mmol/L [from 2.44 mmol/L to 1.77 mmol/L] vs 0.54 mmol/L [from 2.40 mmol/L to 1.86 mmol/L]; P = 0.008). However, there was no difference in HDL-C, triglyceride, or total cholesterol values between groups. Age and LDL-C levels at baseline were significantly associated with target LDL-C achievement.

  • 8.
    Damman, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Koul, Sasha
    Eriksson, Peter
    Erlinge, David
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Patient characteristics and bleeding outcomes in invasively treated acute coronary syndrome patients treated with prasugrel or clopidogrel2012In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 59, no 13, p. E271-E271Article in journal (Other academic)
  • 9.
    Damman, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Koul, Sasha
    Eriksson, Peter
    Erlinge, David
    Lagerqvist, Bo
    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.
    Treatment Patterns and Outcomes in Patients Undergoing Percutaneous Coronary Intervention Treated With Prasugrel or Clopidogrel (from the Swedish Coronary Angiography and Angioplasty Registry [SCAAR])2014In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 113, no 1, p. 64-69Article in journal (Refereed)
    Abstract [en]

    Large real-world registry data are important for understanding the current use and outcomes of novel therapies. The aim of this study was to assess treatment patterns and outcomes in patients who underwent percutaneous coronary intervention (PCI) with prasugrel or clopidogrel. Consecutive patient data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) for 2010 and 2011 were used. The study population consisted of all patients with acute coronary syndromes (ACS) and those without ACS who underwent PCI and were treated with prasugrel (with or without a clopidogrel loading dose) or solely with clopidogrel. Outcomes included were 30-day mortality and in-hospital bleeding. In 2010 and 2011, 23,994 patients were treated with clopidogrel during hospitalization for their first PCI during the study period, while 2,142 patients were treated with prasugrel. Prasugrel was mainly used in patients with ST-segment elevation myocardial infarction. Hemorrhagic risk factors such as older age, female gender, and previous stroke were more common in the clopidogrel-treated patients. However, Mehran bleeding risk scores were higher in prasugrel-treated patients. In the ACS group, lower mortality was observed in the prasugrel group compared with the clopidogrel group. Mortality was comparable in patients who underwent elective angiography and PCI. In-hospital bleeding was lower in prasugrel-treated patients. In conclusion, in this real world population of patients who underwent urgent or elective PCI, prasugrel was used mainly in patients with ACS, while it was avoided in patients with characteristics indicating increased bleeding risk. Mortality and bleeding rates were lower with prasugrel than clopidogrel, probably because of patient selection.

  • 10.
    Edfors, Robert
    et al.
    Karolinska Inst, Dept Med, Stockholm, Sweden;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden.
    Sahlen, Anders
    Karolinska Inst, Dept Med, Stockholm, Sweden;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden;Natl Heart Ctr, Singapore, Singapore.
    Szummer, Karolina
    Karolinska Inst, Dept Med, Stockholm, Sweden;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden.
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Evans, Marie
    Karolinska Inst, Ctr Mol Med, Stockholm, Sweden;Karolinska Inst, Div Renal Med, Stockholm, Sweden.
    Carrero, Juan-Jesus
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Spaak, Jonas
    Karolinska Inst, Danderyd Univ Hosp, Dept Clin Sci, Stockholm, Sweden.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jernberg, Tomas
    Karolinska Inst, Danderyd Univ Hosp, Dept Clin Sci, Stockholm, Sweden.
    Outcomes in patients treated with ticagrelor versus clopidogrel after acute myocardial infarction stratified by renal function2018In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 104, no 19, p. 1575-1582Article in journal (Refereed)
    Abstract [en]

    Objectives We aimed to analyse outcomes of ticagrelor and clopidogrel stratified by estimated glomerular filtration rate (eGFR) in a large unselected cohort of patients with acute myocardial infarction (MI). Methods We used follow-up data in MI survivors discharged on ticagrelor or clopidogrel enrolled in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies registry. The association between ticagrelor versus clopidogrel and the primary composite outcome of death, MI or stroke and the secondary outcome rehospitalisation with bleeding diagnosis at 1year, was studied using adjusted Cox proportional hazards models, stratifying after eGFR levels. Results In total, 45 206 patients with MI discharged on clopidogrel (n=33472) or ticagrelor (n=11734) were included. The unadjusted 1-year event rate for the composite endpoint of death, MI or stroke was 7.0%, 18.0% and 48.0% for ticagrelor treatment and 11.0%, 33.0% and 64.0% for clopidogrel treatment in patients with eGFR(>60) (n=33668), eGFR(30-60) (n=9803) and eGFR(<30) (n=1735), respectively. After adjustment, ticagrelor as compared with clopidogrel was associated with a lower 1-year risk of the composite outcome (eGFR(>60): HR 0.87, 95%CI 0.76 to 99, eGFR(30-60): 0.82 (0.70 to 0.97), eGFR(<30): 0.95 (0.69 to 1.29), P for interaction=0.55) and a higher risk of bleeding (eGFR(>60): HR 1.10, 95%CI 0.90 to 1.35, eGFR(30-60): 1.13 (0.84 to 1.51), eGFR(<30): 1.79 (1.00 to 3.21), P for interaction=0.30) across the eGFR strata. Conclusions Treatment with ticagrelor as compared with clopidogrel in patients with MI was associated with lower risk for the composite of death, MI or stroke and a higher bleeding risk across all strata of eGFR. Of caution, bleeding events were more abundant in patients with eGFR(<30).

  • 11. Erlinge, David
    et al.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Duvvuru, Suman
    Jakubowski, Joseph
    Wanger, Henrik
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Tantry, Udaya
    Brown, Patricia
    Small, David
    Moser, Brian
    Sundseth, Scott
    Walker, Joseph
    Winters, Kenneth
    Gurbel, Paul
    Point-of-Care Genetic Testing of Eleven CYP2C19 Single Nucleotide Polymorphisms Identifies Extensive and Reduced Metabolizers of Clopidogrel With High Accuracy in Patients With Coronary Artery Disease2012In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 60, no 17, p. B211-B212Article in journal (Other academic)
  • 12. Erlinge, David
    et al.
    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.
    Duvvuru, Suman
    Jakubowski, Joseph A.
    Wagner, Henrik
    Varenhorst, Christoph
    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.
    Tantry, Udaya S.
    Brown, Patricia B.
    Small, David
    Moser, Brian A.
    Sundseth, Scott S.
    Walker, Joseph R.
    Winters, Kenneth J.
    Gurbel, Paul A.
    Clopidogrel metaboliser status based on point-of-care CYP2C19 genetic testing in patients with coronary artery disease2014In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 111, no 5, p. 943-950Article in journal (Refereed)
    Abstract [en]

    We compared results obtained with the Nanosphere Verigene (R) System, a novel point-of-care (POC) genetic test capable of analysing 11, CYP2C19 variants within 3 hours, to an established, validated genotyping method (Affymetrix (TM) DMET+; reference assay) for identifying extensive and reduced metabolisers of clopidogrel. Based on genotyping, patients (N=82) with stable coronary artery disease on clopidogrel 75 mg daily were defined as extensive metabolisers (*1/*1, *1/*17,*17/*17), reduced metabolisers (*1/*2,*1/*8,*2/*2,*2/*3), or of indeterminate metaboliser status (*2/*17). Pharmacokinetic exposure to clopidogrel's active metabolite and pharmacodynamic measures with P2Y12 reaction units (PRU) (VerifyNow (R) P2Y12 assay), and VASP PRI (PRI) were also assessed. There was a 99.9% overall; concordance of marker-level data between the Nanosphere Verigene and DMET+ systems in identifying the CYP2C19 variants and 100% agreement in classifying the patients as extensive (n=59) or reduced metabolisers (n=15). Extensive metabolisers had significantly higher active metabolite exposure than reduced metabolisers (LS means 12.6 ng*h/ml vs 7.7 ng*h/ml; p<0.001). Extensive metabolisers also had lower PRU (LS means 158 vs 212; p=0.003) and VASP PRI (LS means 48% vs 63%, p=0.01) compared to reduced metabolisers. Rates of high on-treatment platelet reactivity were higher in reduced metabolisers compared to extensive metabolisers (VASP PRI >= 50%: 79% vs 47%; PRU >235: 33% vs 16%). The Nanosphere Verigene CBS system identified 11 CYP2C19 alleles in less than 3 hours with a high degree of accuracy when compared to a conventional method, and was further validated against pharmacokinetic and pharmacodynamic phenotypes.

  • 13. Erlinge, David
    et al.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Braun, Oscar O
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Winters, Kenneth J
    Jakubowski, Joseph A
    Brandt, John T
    Sugidachi, Atsuhiro
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Patients with poor responsiveness to thienopyridine treatment or with diabetes have lower levels of circulating active metabolite, but their platelets respond normally to active metabolite added ex vivo2008In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 52, no 24, p. 1968-77Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: We evaluated the prevalence and mechanism of poor responsiveness to clopidogrel and prasugrel in coronary artery disease patients with and without diabetes. BACKGROUND: Low platelet inhibition by clopidogrel is associated with ischemic clinical events. A higher 600-mg loading dose (LD) has been advocated to increase responsiveness to clopidogrel. METHODS: In this study, 110 aspirin-treated patients were randomized to double-blind treatment with clopidogrel 600 mg LD/75 mg maintenance dose (MD) for 28 days or prasugrel 60 mg LD/10 mg MD for 28 days. Pharmacodynamic (PD) response was evaluated by light transmission aggregometry and vasodilator-stimulated phosphoprotein phosphorylation. The PD poor responsiveness was defined with 4 definitions previously associated with worse clinical outcomes. Active metabolites (AM) of clopidogrel and prasugrel were measured. Clopidogrel AM was added ex vivo. RESULTS: The proportion of patients with poor responsiveness was greater in the clopidogrel group for all definitions at all time points from 1 h to 29 days. Poor responders had significantly lower plasma AM levels compared with responders. Patients with diabetes were over-represented in the poor-responder groups and had significantly lower levels of AM. Platelets of both poor responders and diabetic patients responded fully to AM added ex vivo. CONCLUSIONS: Prasugrel treatment results in significantly fewer PD poor responders compared with clopidogrel after a 600-mg clopidogrel LD and during MD. The mechanism of incomplete platelet inhibition in clopidogrel poor-responder groups and in diabetic patients is lower plasma levels of its AM and not differences in platelet P2Y(12) receptor function.

  • 14.
    Escaned, Javier
    et al.
    Hosp Clin San Carlos, IDISSC, Madrid, Spain;Univ Complutense Madrid, Madrid, Spain.
    Ryan, Nicola
    Hosp Clin San Carlos, IDISSC, Madrid, Spain;Univ Complutense Madrid, Madrid, Spain.
    Mejia-Renteria, Hernan
    Hosp Clin San Carlos, IDISSC, Madrid, Spain;Univ Complutense Madrid, Madrid, Spain.
    Cook, Christopher M.
    Imperial Coll London, Hammersmith Hosp, London, England.
    Dehbi, Hakim-Moulay
    UCL, CRUK & UCL Canc Trials Ctr, London, England.
    Alegria-Barrero, Eduardo
    Hosp Univ Torrejon, Madrid, Spain;Univ Francisco de Vitoria, Madrid, Spain.
    Alghamdi, Ali
    King Abdulaziz Med City Cardiac Ctr, Riyadh, Saudi Arabia.
    Al-Lamee, Rasha
    Imperial Coll London, Hammersmith Hosp, London, England.
    Altman, John
    Colorado Heart & Vasc, Lakewood, CO USA.
    Ambrosia, Alphonse
    Baptista, Sergio B.
    Hosp Prof Doutor Fernando Fonseca, Amadora, Portugal.
    Bertilsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bhindi, Ravinay
    Royal North Shore Hosp, Sydney, NSW, Australia.
    Birgander, Mats
    Lund Univ, Dept Cardiol, Clin Sci, Skane Univ Hosp, Lund, Sweden.
    Bojara, Waldemar
    Kemperhof Koblenz, Gemeinschaftsklinikum Mittelrhein, Koblenz, Germany.
    Brugaletta, Salvatore
    Inst Invest Biomed August Pi & Sunyer, Hosp Clin, Cardiovasc Inst, Barcelona, Spain.
    Buller, Christopher
    St Michaels Hosp, Toronto, ON, Canada.
    Calais, Fredrik
    Orebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden.
    Silva, Pedro Canas
    Hosp Santa Maria, Lisbon, Portugal.
    Carlsson, Jorg
    Linnaeus Univ, Fac Hlth & Life Sci, Kalmar, Sweden;Kalmar Cty Hosp, Kalmar, Sweden.
    Christiansen, Evald H.
    Aarhus Univ Hosp, Dept Cardiol, Aarhus, Denmark.
    Danielewicz, Mikael
    Karlstad Hosp, Dept Cardiol, Karlstad, Sweden.
    Di Mario, Carlo
    Univ Florence, Florence, Italy;Imperial Coll London, Royal Brompton Hosp, London, England.
    Doh, Joon-Hyung
    Inje Univ, Ilsan Paik Hosp, Daehwa Dong, South Korea.
    Erglis, Andrejs
    Pauls Stradins Clin Univ Hosp, Riga, Latvia.
    Erlinge, David
    Lund Univ, Dept Cardiol, Clin Sci, Skane Univ Hosp, Lund, Sweden.
    Gerber, Robert T.
    Conquest Hosp, St Leonards On Sea, England.
    Going, Olaf
    Sana Klinikum Lichtenberg, Lichtenberg, Germany.
    Gudmundsdottir, Ingibjorg
    Reykjavik Univ Hosp, Dept Cardiol, Reykjavik, Iceland.
    Haerle, Tobias
    Carl von Ossietzky Univ Oldenburg, European Med Sch, Klinikum Oldenburg, Oldenburg, Germany.
    Hauer, Dario
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden;Linkoping Univ, Dept Cardiol, Linkoping, Sweden.
    Hellig, Farrel
    Sunninghill Hosp, Johannesburg, South Africa.
    Indolfi, Ciro
    Magna Graecia Univ Catanzaro, Catanzaro, Italy.
    Jakobsen, Lars
    Aarhus Univ Hosp, Dept Cardiol, Aarhus, Denmark.
    Janssens, Luc
    Imelda Hosp, Bonheiden, Belgium.
    Jensen, Jens
    Sundsvall Hosp, Dept Med, Sundsvall, Sweden;Capio St Gorans Sjukhus, Unit Cardiol, Stockholm, Sweden;Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.
    Jeremias, Allen
    SUNY Stony Brook, Med Ctr, Stony Brook, NY 11794 USA.
    Karegren, Amra
    Vastmanland Hosp Vasteras, Dept Internal Med, Vasteras, Sweden.
    Karlsson, Ann-Charlotte
    Halmstad Cty Hosp, Dept Cardiol, Halmstad, Sweden.
    Kharbanda, Rajesh K.
    Oxford Univ Hosp Fdn Trust, John Radcliffe Hosp, Oxford, England.
    Khashaba, Ahmed
    Ain Shams Univ, Cairo, Egypt.
    Kikuta, Yuetsu
    Fukuyama Cardiovasc Hosp, Fukuyama, Hiroshima, Japan.
    Krackhardt, Florian
    Univ Med, Charite Campus Virchow Klinikum, Berlin, Germany.
    Koo, Bon-Kwon
    Seoul Natl Univ Hosp, Seoul, South Korea.
    Koul, Sasha
    Lund Univ, Dept Cardiol, Clin Sci, Skane Univ Hosp, Lund, Sweden.
    Laine, Mika
    Helsinki Univ Hosp, Helsinki, Finland.
    Lehman, Sam J.
    Flinders Univ S Australia, Adelaide, SA, Australia.
    Lindroos, Pontus
    St Goran Hosp, Dept Cardiol, Stockholm, Sweden.
    Malik, Iqbal S.
    Imperial Coll London, Hammersmith Hosp, London, England.
    Maeng, Michael
    Aarhus Univ Hosp, Dept Cardiol, Aarhus, Denmark.
    Matsuo, Hitoshi
    Gifu Heart Ctr, Gifu, Japan.
    Meuwissen, Martijn
    Amphia Hosp, Breda, Netherlands.
    Nam, Chang-Wook
    Keimyung Univ, Dongsan Med Ctr, Daegu, South Korea.
    Niccoli, Giampaolo
    Univ Cattolica Sacro Cuore, Rome, Italy.
    Nijjer, Sukhjinder S.
    Imperial Coll London, Hammersmith Hosp, London, England.
    Olsson, Hans
    Karlstad Hosp, Dept Cardiol, Karlstad, Sweden.
    Olsson, Sven-Erik
    Helsingborg Hosp, Dept Cardiol, Helsingborg, Sweden;Helsingborg Hosp, Dept Radiol, Helsingborg, Sweden.
    Omerovic, Elmir
    Sahlgrenska Univ Gothenburg, Dept Cardiol, Gothenburg, Sweden.
    Panayi, Georgios
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden;Linkoping Univ, Dept Cardiol, Linkoping, Sweden.
    Petraco, Ricardo
    Imperial Coll London, Hammersmith Hosp, London, England.
    Piek, Jan J.
    Acad Med Ctr, AMC Heart Ctr, Amsterdam, Netherlands.
    Ribichini, Flavo
    Univ Hosp Verona, Verona, Italy.
    Samady, Habib
    Emory Univ, Atlanta, GA 30322 USA.
    Samuels, Bruce
    Cedars Sinai Heart Inst, Los Angeles, CA USA.
    Sandhall, Lennart
    Helsingborg Hosp, Dept Cardiol, Helsingborg, Sweden;Helsingborg Hosp, Dept Radiol, Helsingborg, Sweden.
    Sapontis, James
    MonashHeart, Melbourne, Vic, Australia;Monash Univ, Melbourne, Vic, Australia.
    Sen, Sayan
    Imperial Coll London, Hammersmith Hosp, London, England.
    Seto, Arnold H.
    Vet Affairs Long Beach Healthcare Syst, Long Beach, CA USA.
    Sezer, Murat
    Istanbul Univ, Istanbul Fac Med, Istanbul, Turkey.
    Sharp, Andrew S. P.
    Univ Exeter, Exeter, Devon, England;Royal Devon & Exeter Hosp, Exeter, Devon, England.
    Shin, Eun-Seok
    Univ Ulsan, Coll Med, Ulsan Univ Hosp, Ulsan, South Korea.
    Singh, Jasvindar
    Washington Univ, Sch Med, St Louis, MO USA.
    Takashima, Hiroaki
    Aichi Med Univ Hosp, Nagakute, Aichi, Japan.
    Talwar, Suneel
    Royal Bournemouth Gen Hosp, Bournemouth, Dorset, England.
    Tanaka, Nobuhiro
    Tokyo Med Univ, Tokyo, Japan.
    Tang, Kare
    Anglia Ruskin Univ, Chelmsford, England;Essex Cardiothorac Ctr, Basildon, England.
    Van Belle, Eric
    Lille Univ Hosp, Inst Coeur Poumon, Lille, France;INSERM, Unite 1011, Lille, France.
    van Royen, Niels
    Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Vinhas, Hugo
    Hosp Garcia de Horta, Lisbon, Portugal.
    Vrints, Christiaan J.
    Antwerp Univ Hosp, Antwerp, Belgium.
    Walters, Darren
    Prince Charles Hosp, Brisbane, Qld, Australia.
    Yokoi, Hiroyoshi
    Fukuoka Sannou Hosp, Fukuoka, Japan.
    Frobert, Ole
    Orebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden.
    Patel, Manesh R.
    Duke Univ, Durham, NC USA.
    Serruys, Patrick
    Imperial Coll London, Dept Cardiol, London, England.
    Davies, Justin E.
    Imperial Coll London, Hammersmith Hosp, London, England.
    Gotberg, Matthias
    Lund Univ, Dept Cardiol, Clin Sci, Skane Univ Hosp, Lund, Sweden.
    Safety of the Deferral of Coronary Revascularization on the Basis of Instantaneous Wave-Free Ratio and Fractional Flow Reserve Measurements in Stable Coronary Artery Disease and Acute Coronary Syndromes2018In: JACC: Cardiovascular Interventions, ISSN 1936-8798, E-ISSN 1876-7605, Vol. 11, no 15, p. 1437-1449Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS). BACKGROUND Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization. METHODS The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. RESULTS Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p < 0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04). CONCLUSIONS Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year.

  • 15.
    Grimfjärd, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Vasteras Hosp, Uppsala, Sweden..
    Erlinge, David
    Lund Univ, Skane Univ Hosp, Lund, Sweden..
    Koul, Sasha
    Lund Univ, Skane Univ Hosp, Lund, Sweden..
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Low real-world early stent thrombosis rates in ST-elevation myocardial infarction patients and the use of bivalirudin, heparin alone or glycoprotein IIb/IIIa inhibitor treatment: A nationwide Swedish registry report2016In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 176, p. 78-82Article in journal (Refereed)
    Abstract [en]

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

  • 16.
    Grimfjärd, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Västerås Univ, Dept Cardiol, Västerås, Sweden..
    Erlinge, David
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    Koul, Sasha
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, 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.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Unfractionated heparin versus bivalirudin in patients undergoing primary percutaneous coronary intervention: a SWEDEHEART study2017In: EuroIntervention, ISSN 1774-024X, E-ISSN 1969-6213, Vol. 12, no 16, p. 2009-2017Article in journal (Refereed)
    Abstract [en]

    Aims: The aim of the stud was to compare outcomes in unfractionated heparin (UM) and bivalirudintreated patients undergoing primary percutaneous coronary intervention (PPCI). Methods and results: This observational study contained 20,612 PPCT patients treated with either GM monotherapv or bivalirudin with or without concomitant UFE. Patients with oral anticoagulant or glycoprotein IIb/IIIa inhibitor (GPI) treatment were excluded. The primary outcome measure was definite early stent thrombosis (Si) that occurred at low and similar rates in UNA only and bivalirudin-treated patients: 0.9% vs. 0.8% (adjusted hazard ratio [HR] 1.08, 95% confidence interval [CI]: 0.7-1.65). All-cause death at 30 days occurred in 6.9% vs. 5.4% of patients (adjusted HR 1.23, 95% Cl: 1.05-1.44) and within 365 days in 12.1% vs. 8.9% (adjusted HR 1.34, 95% CI: 1.19-1.52) in the two groups, respectively. The incidence of major bleeding within 30 days was 0.8% vs. 0.6% (adjusted HR 1.54, 95% CI: 0.97-2.45). The incidence of reinfarction within 365 days and stroke within 30 days was similar between groups. Conclusions: In this large, nationwide observational study we found low and similar rates of early ST in UFH only and bivalirudin-treated patients undergoing primary PCI. Mortality was higher in IJFH compared with bivalirudin-treated patients.

  • 17.
    Grimfjärd, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Department of Cardiology, Västerås Hospital, Västerås, Sweden.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Persson, Jonas
    Danderyd Hospital, Department of Cardiology, Stockholm, Sweden.
    Angerås, Oskar
    Sahlgrenska University Hospital, Department of Cardiology, Gothenburg, Sweden.
    Koul, Sasha
    Lund University, Skåne University Hospital, Department of Cardiology, Clinical Sciences, Lund, Sweden.
    Omerovic, Elmir
    Sahlgrenska University Hospital, Department of Cardiology, Gothenburg, 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.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Erlinge, David
    Lund University, Skåne University Hospital, Department of Cardiology, Clinical Sciences, Lund, Sweden.
    Outcome of percutaneous coronary intervention with the Absorb bioresorbable scaffold: data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR)2017In: EuroIntervention, ISSN 1774-024X, E-ISSN 1969-6213, Vol. 13, no 11, p. 1304-1311, article id EIJ-D-17-00458Article in journal (Refereed)
    Abstract [en]

    Aims: Randomised trials indicate higher rates of stent thrombosis (ST) and target lesion failure (TLF) after percutaneous coronary intervention (PCI) with the Absorb bioresorbable scaffold (BRS) compared with modern drug-eluting stents (DES). We aimed to investigate the outcome of all Swedish patients treated with the Absorb BRS.

    Methods and results: The Absorb BRS (n=810) was compared with commonly used modern DES (n=67,909). The main outcome measure was definite ST; mean follow-up was two years. Despite being implanted in a younger, lower-risk population compared with modern DES, the Absorb BRS was associated with a higher crude incidence of definite ST at stent level: 1.5 vs. 0.6%, hazard ratio (HR) 2.38 (95% confidence interval [CI]: 1.34-4.23), adjusted HR 4.34 (95% CI: 2.37-7.94); p<0.001. The patient level adjusted HR was 4.44 (95% CI: 2.25-8.77). Rates of in-stent restenosis were similar for BRS and DES. Non-compliance with dual antiplatelet therapy (DAPT) guidelines was noted in six out of 12 BRS ST events. Three very late ST events occurred with the Absorb BRS.

    Conclusions: In this real-world observational study, the Absorb BRS was associated with a significantly higher risk of definite ST compared with modern DES. Non-compliance with DAPT guideline recommendations was common among Absorb definite ST events.

  • 18.
    Grimfjärd, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Vasteras Hosp, Dept Cardiol, S-72189 Vasteras, Sweden.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Erlinge, David
    Lund Univ, Dept Cardiol, Clin Sci, Skane Univ Hosp, Box 117,Block EA, S-22100 Lund, Sweden.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Pfizer AB Sverige, Vetenskapsvagen 10, S-19138 Sollentuna, Sweden.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Clinical use of cangrelor: nationwide experience from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR)2019In: European Heart Journal - Cardiovascular Pharmacotherapy, ISSN 2055-6837, E-ISSN 2055-6845, Vol. 5, no 3, p. 151-157Article in journal (Refereed)
    Abstract [en]

    Aims This nationwide study aimed to analyse the first 2 years of routine clinical use of cangrelor in all Swedish patients undergoing percutaneous coronary intervention (PCI). Methods and results This observational Swedish Coronary Angiography and Angioplasty Registry (SCAAR) study identified 915 cangrelor-treated patients. As 899 were ST-segment elevation myocardial infarction (STEMI)-patients undergoing primary PCI, we decided to exclude all non-STEMI patients (n=16) from the following analysis. We then identified all primary PCI patients, January 2016 to January 2018 (n=10816). Excluding hospitals without cangrelor use, tailoring time frames from first cangrelor use per hospital, patients treated with cangrelor (n=899) were compared with those without cangrelor treatment (n=4614). A separate analysis was performed for cardiac arrest STEMI patients (n=273). Cangrelor-use in primary PCI varied greatly between hospitals (4-36%, mean 16%). At variance with randomized trials, cangrelor was used nearly exclusively in STEMI, often with cardiac arrest (19%). Cangrelor was combined with ticagrelor in two-thirds of patients, among which >50% was prehospital. Cangrelor was used more frequently in high-risk patients: left main PCI, thrombus aspiration, and cardiac arrest. Despite cangrelor being used in more high-risk patients, crude definite stent thrombosis rates at 30days were low and similar in cangrelor (0.7%) and non-cangrelor treated patients (0.8%). Conclusion Cangrelor was used nearly exclusively in primary PCI STEMI patients, predominantly with ticagrelor. Despite being used in very high-risk patients, often with cardiac arrest, cangrelor treatment was associated with low stent thrombosis rates.

  • 19. Grove, Erik L
    et al.
    Lankeit, Mareike
    Hess, Katharina
    Freynhofer, Matthias
    Stojkovic, Stefan
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Thomas, Mark
    CardioPulse: the 'Young Thrombosis Researchers Group' of the ESC Working Group on Thrombosis2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no 12, p. 703-704Article in journal (Refereed)
  • 20.
    Gudnadottir, Gudny Stella
    et al.
    Sahlgrens Univ Hosp, Dept Geriatr, Gothenburg, Sweden;Landspitali Univ Hosp, Dept Cardiol, Reykjavik, Iceland;Landspitali Univ Hosp, Cardiovas Res Ctr, Reykjavik, Iceland;Univ Iceland, Sch Hlth Sci, Reykjavik, Iceland.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Andersen, Karl
    Landspitali Univ Hosp, Dept Cardiol, Reykjavik, Iceland;Landspitali Univ Hosp, Cardiovas Res Ctr, Reykjavik, Iceland;Univ Iceland, Sch Hlth Sci, Reykjavik, Iceland.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Thrainsdottir, Inga Sigurros
    Landspitali Univ Hosp, Dept Cardiol, Reykjavik, Iceland;Landspitali Univ Hosp, Cardiovas Res Ctr, Reykjavik, Iceland.
    Ravn-Fischer, Annica
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Pfizer AB, Sollentuna, Sweden.
    Gudnason, Thorarinn
    Landspitali Univ Hosp, Dept Cardiol, Reykjavik, Iceland;Landspitali Univ Hosp, Cardiovas Res Ctr, Reykjavik, Iceland;Univ Iceland, Sch Hlth Sci, Reykjavik, Iceland.
    Outcomes after STEMI in old multimorbid patients with complex health needs and the effect of invasive management2019In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 211, p. 11-21Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 21.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Eriksson, Niclas
    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.
    Johansson, Åsa
    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 Immunology, Genetics and Pathology, Genomics.
    Bertilsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Axelsson, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Barratt, Bryan J.
    Becker, Richard C.
    Himmelmann, Anders
    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.
    Katus, Hugo A.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Steg, Philippe G.
    Storey, Robert F.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Åkerblom, Axel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Are There Any Causal Relations Between Growth Differentiation Factor 15 and Outcomes in Patients With Acute Coronary Syndrome?: - A Report From the Plato Gwas Study2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 22Article in journal (Other academic)
  • 22.
    Hambraeus, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jensevik, Karin
    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.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Carlsson, Roland
    Department of Cardiology, Karlstad.
    Farzaneh-Far, Ramin
    Gilead Sciences,Inc.
    Kellerth, Thomas
    Department of Cardiology University Hospital Örebro Sweden.
    Omerovic, Elmir
    Department of Cardiology, Sahlgrenska University Hospital, Gothenburg.
    Stone, Gregg
    Cardiovascular Research Foundation, New York.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, 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.
    Long-Term Outcome of Incomplete Revascularization After Percutaneous Coronary Intervention in SCAAR (Swedish Coronary Angiography and Angioplasty Registry)2016In: JACC: Cardiovascular Interventions, ISSN 1936-8798, E-ISSN 1876-7605, Vol. 9, no 3, p. 207-215Article in journal (Other academic)
    Abstract [en]

    OBJECTIVES The aim of this study was to describe current practice regarding completeness of revascularization in patients with multivessel disease undergoing percutaneous coronary intervention (PCI) and to investigate the association of incomplete revascularization (IR) with death, repeat revascularization, and myocardial infarction (MI) in a large nationwide registry. BACKGROUND The benefits of multivessel PCI are controversial. METHODS Between 2006 and 2010 we identified 23,342 patients with multivessel disease in the SCAAR (Swedish Coronary Angiography and Angioplasty Registry) and merged data with official Swedish health data registries. IR was defined as any nontreated significant (60%) stenosis in a coronary artery supplying > 10% of the myocardium. RESULTS Patients with IR (n = 15,165) were older, had more extensive coronary disease, and more often had ST-segment elevation MI at presentation than those with complete revascularization (CR) (n = 8,177). All-cause 1-year mortality, MI, and repeat revascularization were higher in IR than CR: 7.1% versus 3.8%, 10.4% versus 6.0%, and 20.5% versus 8.5%, respectively. Propensity score methodology was used in the adjusted analyses. Adjusted hazard ratio (HR) for the composite of death, MI, or repeat revascularization at 1 year was higher in IR than CR: 2.12 (95% confidence interval [CI]: 1.98 to 2.28; p < 0.0001). Adjusted HR for death and the combination of death/MI were 1.29 (95% CI: 1.12 to 1.49; p = 0.0005) and 1.42 (95% CI: 1.30 to 1.56; p < 0.0001), respectively. CONCLUSIONS Incomplete revascularization at the time of hospital discharge in patients with multivessel disease undergoing PCI is associated with a high risk of recurrent 1-year adverse cardiac events.

  • 23. Ibanez, Borja
    et al.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Agewall, Stefan
    Antunes, Manuel J.
    Bucciarelli-Ducci, Chiara
    Bueno, Hector
    Caforio, Alida L. P.
    Crea, Filippo
    Goudevenos, John A.
    Halvorsen, Sigrun
    Hindricks, Gerhard
    Kastrati, Adnan
    Lenzen, Mattie J.
    Prescott, Eva
    Roffi, Marco
    Valgimigli, Marco
    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.
    Vranckx, Pascal
    Widimsky, Petr
    2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC)2018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 2, p. 119-177Article in journal (Refereed)
  • 24.
    Johansson, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Becker, Richard C.
    Storey, Robert F.
    Himmelmann, Anders
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Axelsson, Tomas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Barratt, Bryan J.
    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.
    Steg, Philippe Gabriel
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    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.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    NLRC4 Inflammasome Is an Important Regulator of Interleukin-18 Levels in Patients With Acute Coronary Syndromes Genome-Wide Association Study in the PLATelet inhibition and patient Outcomes Trial (PLATO)2015In: Circulation: Cardiovascular Genetics, ISSN 1942-325X, E-ISSN 1942-3268, Vol. 8, no 3, p. 498-506Article in journal (Refereed)
    Abstract [en]

    Background Interleukin 18 (IL-18) promotes atherosclerotic plaque formation and is increased in patients with acute coronary syndromes. However the relative contribution of genetic variants to the IL-18 levels has not been fully determined. Methods and Results Baseline plasma IL-18 levels were measured in 16633 patients with acute coronary syndrome, of whom 9340 had genetic data that passed genotype quality control. A 2-stage genome-wide association study was performed, followed by combined analyses using >10 million genotyped or imputed genetic markers. Single nucleotide polymorphisms at 3 loci (IL18, NLRC4, and MROH6) were identified (P<3.15x10(-8)) in the discovery cohort (n=3777) and replicated in the remaining patients (n=5563). In the pooled data (discovery+replication cohort), 7 independent associations, in 5 chromosomal regions, were associated with IL-18 levels (minimum P=6.99x10(-72)). Six single nucleotide polymorphisms are located in predicted promoter regions of which one disrupts a transcription factor binding site. One single nucleotide polymorphism in NLRC4 is a rare missense variant, predicted to be deleterious to the protein. Altogether, the identified genetic variants explained 8% of the total variation in IL-18 levels in the cohort. Conclusions Our results show that genetic variants play an important role in determining IL-18 levels in patients with acute coronary syndrome and we have identified genetic variants located in the IL-18 gene (IL18) or close to genes that are involved in procaspase-1 activation (NLRC4 and CARD16, CARD17, and CARD18). These associations also highlight the importance of the NLRC4 inflammasome for IL-18 production in acute coronary syndrome patients.

  • 25.
    Johansson, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindholm, Daniel
    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.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Axelsson, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Barratt, Bryan J.
    AstraZeneca R&D, Alderley Pk SK10 4TF, Cheshire, England..
    Becker, Richard C.
    Acad Hlth Ctr, Div Cardiovasc Hlth & Dis, Heart Lung & Vasc Inst, Cincinnati, OH 45267 USA..
    Himmelmann, Anders
    AstraZeneca Res & Dev, S-43150 Molndal, Sweden..
    Katus, Hugo A.
    Univ Klinikum Heidelberg, Med Klin, D-69120 Heidelberg, Germany..
    Steg, Philippe Gabriel
    INSERM, Unite 1148, F-75019 Paris, France.;Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, F-75018 Paris, France.;Univ Paris Diderot, Sorbonne Paris Cite, F-75013 Paris, France.;Royal Brompton Hosp, ICMS, NHLI Imperial Coll, London SW3 6NP, England..
    Storey, Robert F.
    Univ Sheffield, Dept Cardiovasc Sci, Sheffield S10 2RX, 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.
    Genome-wide association and Mendelian randomization study of NT-proBNP in patients with acute coronary syndrome2016In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 25, no 7, p. 1447-1456Article in journal (Refereed)
    Abstract [en]

    N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a strong predictor of mortality in coronary artery disease and is widely employed as a prognostic biomarker. However, a causal relationship between NT-proBNP and clinical endpoints has not been established. We have performed a genome-wide association and Mendelian randomization study of NT-proBNP. We used a discovery set of 3740 patients from the PLATelet inhibition and patient Outcomes (PLATO) trial, which enrolled 18 624 patients with acute coronary syndrome (ACS). A further set of 5492 patients, from the same trial, was used for replication. Genetic variants at two novel loci (SLC39A8 and POC1B/GALNT4) were associated with NT-proBNP levels and replicated together with the previously known NPPB locus. The most significant SNP (rs198389, pooled P = 1.07 x 10(-15)) in NPPB interrupts an E-box consensus motif in the gene promoter. The association in SLC39A8 is driven by a deleterious variant (rs13107325, pooled P = 5.99 x 10(-10)), whereas the most significant SNP in POC1B/GALNT4 (rs11105306, pooled P = 1.02 x 10(-16)) is intronic. The SLC39A8 SNP was associated with higher risk of cardiovascular (CV) death (HR = 1.39, 95% CI: 1.08-1.79, P = 0.0095), but the other loci were not associated with clinical endpoints. We have identified two novel loci to be associated with NT-proBNP in patients with ACS. Only the SLC39A8 variant, but not the NPPB variant, was associated with a clinical endpoint. Due to pleotropic effects of SLC39A8, these results do not suggest that NT-proBNP levels have a direct effect on mortality in ACS patients. PLATO Clinical Trial Registration: ; NCT00391872.

  • 26.
    Johnston, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sarno, Giovanna
    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.
    Larsson, Bertil
    Bild- och funktionsmedicinskt centrum, Akademiska sjukhuset, Uppsala, Sweden.
    Tornvall, Per
    Varenhorst, Christoph
    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.
    Spontan kranskärls­dissektion kan orsaka akut koronart syndrom: ovanligt tillstånd som kräver genomtänkt handläggning och mer forskning2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, article id DRFWArticle in journal (Refereed)
    Abstract [en]

    Spontaneous coronary artery dissection (SCAD) is a non-traumatic and non-iatrogenic injury occurring in the vessel wall caused by either a primary intimal dissection or a primary hematoma in the medial layer. SCAD is more common among women than men and accounts for a small minority of acute coronary syndromes. The causes of SCAD are multifactorial. Peripartum SCAD is most common. Fibromuscular dysplasia has a strong association with SCAD. As spontaneous healing is common in SCAD and PCI is associated with complications an initial conservative approach should always be considered. Medical treatment is based on the underlying cause. Beta blockers are recommended to all patients. The prognosis varies; the highest mortality is reported among women suffering peripartum SCAD. Quality of life is often affected in SCAD patients and accompanied by a high rate of rehospitalizations. More research which focuses on the underlying causes, optimal treatment and rehabilitation is needed.

  • 27. Klerdal, Kristina
    et al.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alfredsson, Lars
    Blomberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Moradi, Tahereh
    Sex as a determinant of prehospital ECG in ST- and non-ST elevation myocardial infarction patients2014In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 100, no 22, p. 1817-1818Article in journal (Refereed)
  • 28.
    Lindholm, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alfredsson, Joakim
    Linkoping Univ, Dept Cardiol, Linkoping, Sweden; Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.
    Angerås, Oskar
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden.
    Böhm, Felix
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Div Cardiol, Stockholm, Sweden.
    Calais, Fredrik
    Orebro Univ, Dept Cardiol, Fac Hlth, Orebro, Sweden.
    Koul, Sasha
    Lund Univ, Dept Cardiol, Clin Sci, Lund, 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.
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sarno, Giovanna
    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.
    Timing of percutaneous coronary intervention in patients with non-ST-elevation myocardial infarction: a SWEDEHEART study2017In: European Heart Journal - Quality of Care and Clinical Outcomes, ISSN 2058-5225, E-ISSN 2058-1742, Vol. 3, no 1, p. 53-60Article in journal (Refereed)
    Abstract [en]

    Aims

    Although routine invasive management is recommended in NSTEMI patients, the optimal timing of the procedure is not defined. The aim of this study was to assess outcomes in relation to timing of PCI in NSTEMI patients.

    Methods and results

    This was an observational, prospective, multicentre cohort study from the SWEDEHEART registry including all Swedish PCI centres. We included 40 494 consecutive PCI-treated patients who were admitted to any coronary care unit from 2006 to 2013. The primary outcome was all-cause death, and secondary outcomes were recurrent myocardial infarction (MI), stent thrombosis, and severe in-hospital bleeding. Outcomes were assessed within 1 year from admission in relation to pre-specified cut-offs to define early PCI: within 1, 2, or 3 days. Patients who received delayed PCI, compared with those who did not, were older, and had a higher prevalence of comorbidities (hypertension, hyperlipidaemia, diabetes, and prior stroke) but showed similar angiographic findings. Cox mixed-effects models showed a lower risk of all-cause death with early PCI across all three cut-offs: HR (95% CI) of 0.88 (0.80–0.98), 0.78 (0.71–0.86), and 0.75 (0.68–0.84), for the 1-, 2-, and 3-day cut-offs, respectively. Early PCI was associated with lower risk of recurrent MI for the 2- and 3-day cut-offs, but not for the 1-day cut-off. The reported rates of severe in-hospital bleeding were low, but tended to be higher in patients receiving delayed PCI.

    Conclusion

    In patients undergoing PCI for NSTEMI, early invasive treatment is associated with lower risk of ischaemic outcomes.

  • 29.
    Lindholm, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Andersson, Jonas
    Heartcenter, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
    Braun, Oscar Ö
    Department of Cardiology, Clinical Sciences, Faculty of Medicine, Lund University, Skåne University Hospital, Lund, Sweden.
    Heller, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Henriksson, Peter
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Lauermann, Jörg
    Department of Internal Medicine, Division of Cardiology, Ryhov Hospital, Jönköping, Sweden.
    Öhagen, Patrik
    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. Pfizer, Stockholm, Sweden.
    Caffeine and incidence of dyspnea in patients treated with ticagrelor2018In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 200, p. 141-143Article in journal (Refereed)
  • 30.
    Lindholm, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindback, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Becker, R. C.
    Acad Med Ctr, Heart Lung & Vasc Inst, Div Cardiovasc Hlth & Dis, Cincinnati, OH USA..
    Himmelmann, A.
    AstraZeneca, Res & Dev, Molndal, Sweden..
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Steg, P. G.
    INSERM, U1148, Paris, France. Univ Paris Diderot, Hop Bichat, AP HP, FIRE,NHLI Imperial Coll,INSERM,U1148, Paris, France..
    Katus, H. A.
    Univ Heidelberg Hosp, Med Klin, Heidelberg, Germany..
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Biomarker-based prediction model for recurrent ischemic events in revascularised patients with acute coronary syndromes2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no Suppl. 1, p. 10-11Article in journal (Other academic)
  • 31.
    Lindholm, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindbäck, Johan
    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.
    Becker, Richard
    Cornel, Jan
    Himmelmann, Anders
    Giannitsis, Evangelos
    Harrington, Robert
    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.
    Husted, Steen
    Katus, Hugo
    Mahaffey, Kenneth
    Steg, Philippe Gabriel
    Storey, Robert
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Prediction Of Major Bleeding In Revascularized Patients With Acute Coronary Syndromes: Development Of A Novel Biomarker-Based Clinical Prediction Model2016In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 67, no 13, p. 493-493Article in journal (Other academic)
  • 32.
    Lindholm, Daniel P
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    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.
    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.
    Hlatky, Mark A
    Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
    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.
    New Method for Assessing the Effect of Driving Distance to Hospital Care: Using OpenStreetMap Routing in Cardiovascular Research2017In: Circulation. Cardiovascular Quality and Outcomes, ISSN 1941-7713, E-ISSN 1941-7705, Vol. 10, no 9, article id e003850Article in journal (Refereed)
  • 33.
    Lindholm, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Storey, Robert F.
    Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England..
    Christersson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala Univ, Dept Med Sci, Cardiol, Uppsala, Sweden..
    Halvorsen, Sigrun
    Oslo Univ Hosp Ulleval, Dept Cardiol, Oslo, Norway.;Univ Oslo, Oslo, Norway..
    Grove, Erik L.
    Aarhus Univ Hosp, Dept Cardiol, DK-8000 Aarhus, Denmark..
    Braun, Oscar O.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, 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.
    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.
    Design and rationale of TROCADERO: A TRial Of Caffeine to Alleviate DyspnEa Related to ticagrelOr2015In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 170, no 3, p. 465-470Article in journal (Refereed)
    Abstract [en]

    Background Ticagrelor treatment has the side effect of increased incidence of dyspnea. Adenosine-induced dyspnea is augmented by ticagrelor and can be alleviated with the adenosine antagonist theophylline. Caffeine is a closely related xanthine derivative. Objectives The primary objective of the TROCADERO is to evaluate the effect of caffeine versus placebo on ticagrelorassociated dyspnea, measured by the visual analog scale area under the curve in patients with ongoing ticagrelor treatment after an acute coronary syndrome event. Design After a run-in period of 1 to 7 days of absence of caffeine intake, acute coronary syndrome patients with ticagrelorinduced dyspnea (planned inclusion 416) are randomized in a blinded fashion to either caffeine 200 mg twice daily or matching placebo with a treatment duration of 1 week. The primary efficacy end point is change in visual analog scale area under the curve for dyspnea, and the primary safety end point is occurrence of high on-treatment platelet reactivity measured by the VerifyNow P2Y12 assay. Conclusions This trial will determine if adenosine antagonism by caffeine can alleviate ticagrelor-related dyspnea, without impairing the antiplatelet effect of ticagrelor.

  • 34.
    Lindholm, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Cannon, Christopher
    Harrington, Robert
    Himmelmann, Anders
    Maya, Juan
    Husted, Steen
    Katus, Hugo
    Steg, Philippe
    Storey, Robert
    Wallentin, Lars
    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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ticagrelor versus clopidogrel in patients with non-st-elevation acute coronary syndrome: results from the PLATO trial2013In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 61, no 10, p. E1-E1Article in journal (Other academic)
  • 35.
    Lindholm, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Cannon, Christopher P.
    Harrington, Robert A.
    Himmelmann, Anders
    Maya, Juan
    Husted, Steen
    Steg, Philippe Gabriel
    Cornel, Jan H.
    Storey, Robert F.
    Stevens, Susanna R.
    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.
    Ticagrelor vs. clopidogrel in patients with non-ST-elevation acute coronary syndrome with or without revascularization: results from the PLATO trial2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, no 31, p. 2083-2093Article in journal (Refereed)
    Abstract [en]

    Aims The optimal platelet inhibition strategy for ACS patients managed without revascularization is unknown. We aimed to evaluate efficacy and safety of ticagrelor vs. clopidogrel in the non-ST-elevation acute coronary syndrome (NSTE-ACS) subgroup of the PLATO trial, in the total cohort, and in the subgroups managed with and without revascularization within 10 days of randomization. Methods and results We performed a retrospective analysis of the primary endpoint of cardiovascular death/myocardial infarction/stroke. Among 18 624 PLATO patients, 11 080 (59%) were categorized as NSTE-ACS at randomization. During the initial 10 days, 74% had angiography, 46% PCI, and 5% CABG. In NSTE-ACS patients, the primary endpoint was reduced with ticagrelor vs. clopidogrel [10.0 vs. 12.3%; hazard ratio (HR) 0.83; 95% confidence interval (CI) = 0.74-0.93], as was myocardial infarction (6.6 vs. 7.7%; HR 0.86; 95% CI = 0.74-0.99), cardiovascular death (3.7 vs. 4.9%; HR 0.77; 95% CI = 0.64-0.93), and all-cause death (4.3 vs. 5.8%; HR 0.76; 95% CI = 0.64-0.90). Major bleeding rate was similar between treatment groups (13.4 vs. 12.6%; HR 1.07; 95% CI = 0.95-1.19), but ticagrelor was associated with an increase in non-CABG major bleeding (4.8 vs. 3.8%; HR 1.28; 95% CI = 1.05-1.56). Within the first 10 days, 5366 (48.4%) patients were managed without revascularization. Regardless of revascularization or not, ticagrelor consistently reduced the primary outcome (HR 0.86 vs. 0.85, interaction P = 0.93), and all-cause death (HR 0.75 vs. 0.73, interaction P = 0.89) with no significant increase in overall major bleeding. Conclusion In patients with NSTE-ACS, benefit of ticagrelor over clopidogrel in reducing ischaemic events and total mortality was consistent with the overall PLATO trial, independent of actually performed revascularization during the initial 10 days.

  • 36.
    Oskarsson, A.
    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.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wernroth, Mona-Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Becker, R. C.
    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.
    Storey, R. F.
    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.
    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.
    ApoA1 is independently associated with recurrent ischemic events and death in acute coronary syndrome patients2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, p. 482-482Article in journal (Refereed)
  • 37.
    Sahlen, Anders
    et al.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden.;Natl Heart Ctr Singapore, 5 Hosp Dr, Singapore 169609, Singapore..
    Varenhorst, Christoph
    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.
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Omerovic, Elmir
    Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden..
    Erlinge, David
    Lund Univ, Clin Sci, Dept Cardiol, Lund, Sweden..
    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.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jernberg, Tomas
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Outcomes in patients treated with ticagrelor or clopidogrel after acute myocardial infarction: experiences from SWEDEHEART registry2016In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 37, no 44, p. 3335-3342Article in journal (Refereed)
    Abstract [en]

    Aims Ticagrelor reduces ischaemic events and mortality in acute coronary syndrome (ACS) vs. clopidogrel. We wished to study clinical outcomes in a large real-world population post-ACS. Methods and results We performed a prospective cohort study in 45 073 ACS patients enrolled into SwedishWeb system for Enhancement and Development of Evidence-based care in Heart Disease Evaluated According to Recommended Therapies who were discharged on ticagrelor (N = 11 954) or clopidogrel (N = 33 119) between 1 January 2010 and 31 December 2013. The primary outcome was a composite of all-cause death, re-admission with myocardial infarction (MI) or stroke, secondary outcomes as the individual components of the primary outcome, and re-admission with bleeding. The risk of the primary outcome with ticagrelor vs. clopidogrel was 11.7 vs. 22.3% (adjusted hazard ratio (HR) 0.85 [95% confidence interval: 0.78-0.93]), risk of death 5.8 vs. 12.9% (adjusted HR 0.83 [0.75-0.92]), and risk of MI 6.1 vs. 10.8% (adjusted HR 0.89 [0.78-1.01]) at 24 months. Re-admission with bleeding with ticagrelor vs. clopidogrel occurred in 5.5 vs. 5.2% (adjusted HR 1.20 [1.04-1.40]). In a subset of patients undergoing percutaneous coronary intervention (PCI) on ticagrelor vs. clopidogrel the PCI-related in-hospital bleeding was 3.7 vs. 2.7% (adjusted odds ratio, OR, 1.57 [1.30-1.90]). Conclusion Ticagrelor vs. clopidogrel post-ACS was associated with a lower risk of death, MI, or stroke, as well as death alone. Risk of bleeding was higher with ticagrelor. These real-world outcomes are consistent with randomized trial results.

  • 38.
    Sarno, Giovanna
    et al.
    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.
    Nilsson, Johan
    Frobert, Ole
    Hambraeus, Kristina
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jensen, Ulf J.
    Todt, Tim
    Gotberg, Matthias
    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.
    Stent Thrombosis in New-Generation Drug-Eluting Stents in Patients With STEMI Undergoing Primary PCI2014In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 64, no 1, p. 16-24Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Some concerns still have not been resolved about the long-term safety of drug-eluting stents (DES) in patients with acute STEMI. OBJECTIVES The aim of this study was to evaluate the stent thrombosis (ST) rate up to 3 years in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI) with new-generation drug-eluting stents (n-DES) compared with bare-metal stents (BMS) and old-generation drug-eluting stents (o-DES) enrolled in the SCAAR (Swedish Coronary Angiography and Angioplasty Registry). METHODS From January 2007 to January 2013, 34,147 patients with STEMI were treated by PCI with n-DES (n = 4,811), o-DES (n = 4,271), or BMS (n = 25,065). The risks of early/late (up to 1 year) and very late definite ST (after 1 year) were estimated. RESULTS Cox regression landmark analysis showed a significantly lower risk of early/late ST in patients treated with n-DES (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.43 to 0.99; p 0.04) and o-DES (HR: 0.60; 95% CI: 0.41 to 0.89; p = 0.01) compared with the BMS group. The risk of very late ST was similar between the n-DES and BMS groups (HR: 1.52; 95% CI: 0.78 to 2.98; p = 0.21), whereas a higher risk of very late ST was observed with o-DES compared with BMS (HR: 2.88; 95% CI: 1.70 to 4.89; p < 0.01). CONCLUSIONS Patients treated with n-DES have a lower risk of early/late ST than patients treated with BMS. The risk of very late ST is low and comparable between n-DES and BMS up to 3 years of follow-up, whereas o-DES treatment is associated with an increased risk of very late ST. The current STEMI guidelines might require an update in light of the results of this and other recent studies. 

  • 39.
    Sarno, Giovanna
    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.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Olivecrona, Göran
    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.
    Danielewicz, Mikael
    Hambraeus, Kristina
    Lindholm, Daniel
    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.
    Råmunddal, Truls
    Witt, Nils
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Real-life clinical outcomes with everolimus eluting platinum chromium stent with an abluminal biodegradable polymer in patients from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR)2017In: Catheterization and cardiovascular interventions, ISSN 1522-1946, E-ISSN 1522-726X, Vol. 90, no 6, p. 881-887Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: No previous studies have evaluated the performance of the Synergy stent in a large real-life population.

    OBJECTIVES: To describe the initial real-life experience with a novel everolimus eluting platinum chromium stent with abluminal biodegradable polymer (SYNERGY) in unselected patients from a nationwide registry.

    METHODS: All implanted Synergy stents were compared with other new generation drug eluting stents (n-DES) with >1,000 implantations in Sweden between March 2013 and October 2015. Restenosis, definite stent thrombosis (ST), myocardial infarction (MI) and death rates were assessed using propensity score and Cox regression analyses.

    RESULTS: A total of 7,886 of Synergy stents and 64,429 other n-DES (BioMatrix, N = 1,953; Orsiro, N = 4,946; Promus Element Plus, N= 2,543; Promus Premier, N= 20,414; Xience Xpedition, N= 7,971, Resolute/Resolute Integrity, N = 19,021; Ultimaster, N = 1,156; Resolute Onyx, N = 6,425) were implanted in 42,357 procedures. Restenosis and stent thrombosis occurred in 642 and 314 cases, respectively, in the overall population at 1 year. The cumulative rate of restenosis (1.1% vs. 1.0%, adjusted HR: 1.24 95% CI: 0.88-1.75; P = 0.21) and ST (0.4% vs. 0.5%, adjusted HR: 0.97; 95% CI: 0.63-1.50; P = 0.17) up to 1 year was low in both the Synergy group and the other n-DES group. Death occurred in 5.2% versus 4.5% (adjusted HR: 1.14; 95% CI: 0.96-1.36; P = 0.11) and MI in 3.2% versus 3.5%, (adjusted HR: 1.11; 95% CI: 0.93-1.33; P = 0.24) up to 1 year.

    CONCLUSIONS: In a large real-life population the Synergy stent appears to be safe and effective with a low rate of restenosis and ST comparable with other n-DES.

  • 40.
    Siegbahn, Agneta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Åkerblom, Axel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Bertilsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Axelsson, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Barratt, Bryan J.
    Becker, Richard C.
    Himmelmann, Anders
    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.
    Katus, Hugo A.
    Steg, Philippe G.
    Storey, Robert F.
    Syvanen, Ann-Christine
    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.
    Evaluation of the Effect of Interleukin 18 Associated Genetic Polymorphisms on Risk of Cardiovascular Events in Patients With Acute Coronary Syndrome2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 22Article in journal (Other academic)
  • 41. Storey, Robert F
    et al.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    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.
    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.
    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.
    Ycas, Joseph
    Husted, Steen E
    Cannon, Christopher P
    Becker, Richard C
    Steg, Ph Gabriel
    Åsenblad, Nils
    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.
    Lower mortality following pulmonary adverse events and sepsis with ticagrelor compared to clopidogrel in the PLATO study2014In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 25, no 7, p. 517-525Article in journal (Refereed)
    Abstract [en]

    In the PLATelet inhibition and patient Outcomes (PLATO) study of patients with acute coronary syndromes, ticagrelor reduced mortality compared to clopidogrel but the mechanisms for this mortality reduction remain uncertain. We analysed adverse events (AEs) consistent with either pulmonary infection or sepsis, and subsequent mortality, in 18,421 PLATO patients treated with ticagrelor or clopidogrel. AEs occurring within 7 days of last dose of study medication were defined as "on-treatment". Serial measurements of blood leukocyte counts, C-reactive protein and interleukin-6 were performed. Fewer on-treatment pulmonary AEs occurred in the ticagrelor compared to the clopidogrel group (275 vs. 331 respectively; p = 0.019), with fewer deaths following these AEs (33 vs. 71; p < 0.001), particularly in those who remained on study medication three days after AE onset (10 vs. 43; p < 0.001). There were fewer deaths attributed to sepsis in the ticagrelor group (7 vs. 23; p = 0.003). Leukocyte counts were lower in the clopidogrel group during treatment (p < 0.0001 at 1, 3 and 6 months) but not at 1 month post-discontinuation. C-reactive protein increased more at discharge in the ticagrelor group (28.0 ± 38.0 vs. 26.1 ± 36.6 mg/l; p < 0.001) and interleukin-6 remained higher during the first month of treatment with ticagrelor. We conclude that the mortality risk following pulmonary AEs and sepsis in acute coronary syndrome patients appears to be lower during ticagrelor compared to clopidogrel therapy. Further work should assess whether ticagrelor and clopidogrel have differential effects on immune signalling.

  • 42.
    Ueda, Peter
    et al.
    Karolinska Inst, Dept Med, Clin Epidemiol Div, Eugeniahemmet T2, S-17176 Stockholm, Sweden.
    Jernberg, Tomas
    Karolinska Inst, Danderyd Univ Hosp, Dept Clin Sci, Div Cardiovasc Med, Stockholm, Sweden.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alfredsson, Joakim
    Linkoping Univ, Dept Cardiol, Linkoping, Sweden;Linkoping Univ, Fac Hlth Sci, Dept Med & Hlth Sci, Linkoping, Sweden.
    Erlinge, David
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden.
    Omerovic, Elmir
    Sahlgrens Univ Hosp, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden.
    Persson, Jonas
    Karolinska Inst, Danderyd Univ Hosp, Dept Clin Sci, Div Cardiovasc Med, Stockholm, Sweden.
    Ravn-Fischer, Annica
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden.
    Tornvall, Per
    Karolinska Inst, Dept Clin Sci & Educ, Sodersjukhuset, Stockholm, Sweden.
    Svennblad, Bodil
    Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Pfizer AB, Sollentuna, Sweden.
    External Validation of the DAPT Score in a Nationwide Population2018In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 72, no 10, p. 1069-1078Article in journal (Refereed)
    Abstract [en]

    BACKGROUND The dual antiplatelet therapy (DAPT) score guides decisions on DAPT duration after coronary stenting by simultaneously predicting ischemic and bleeding risk. OBJECTIVES This study sought to assess the performance of the DAPT score in a nationwide real-world population. METHODS The study used register data in Sweden (2006 to 2014) and followed 41,101 patients who had undergone 12 months of event-free DAPT, from months 12 to 30 after stenting. Risk of myocardial infarction (MI) or stent thrombosis, major adverse cardiovascular and cerebrovascular events (MACCE) (MI, stroke, and all-cause death), and fatal or major bleeding were compared according to DAPT score. RESULTS The score had a discrimination of 0.58 (95% confidence interval [CI]: 0.56 to 0.60) for MI or stent thrombosis, 0.54 (95% CI: 0.53 to 0.55) for MACCE, and 0.49 (95% CI: 0.45 to 0.53) for fatal or major bleeding. Risk of MI or stent thrombosis was significantly increased at scores of >= 3 while MACCE risk followed a J-shaped pattern and increased at scores of >= 4. Absolute differences in fatal or major bleeding risk were small between scores. Event rates of ischemic and bleeding outcomes in patients with high (>= 2) and low (< 2) scores differed compared to the DAPT Study from which the score was derived; fatal or major bleeding rates were approximately one-half of those in the placebo arm of the DAPT Study. CONCLUSIONS In a nationwide population, the DAPT score did not adequately discriminate ischemic and bleeding risk, the relationship between score and ischemic risk did not correspond to the suggested decision rule for extended DAPT, and risk of bleeding was lower compared with the DAPT Study. The score and its decision rule may not be generalizable to real-world populations.

  • 43.
    Varenhorst, Christoph
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alfredsson, Joakim
    Angerås, Oskar
    Bohm, Felix
    Calais, Fredrik
    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.
    Koul, Sasha
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sarno, Giovanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindholm, Daniel
    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.
    Timing Of Pci In Patients With Non-St-Elevation Myocardial Infarction: A Swedeheart Study2016In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 67, no 13, p. 44-44Article in journal (Other academic)
  • 44.
    Varenhorst, Christoph
    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.
    Alström, Ulrica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Braun, O. O.
    Storey, R. F.
    Mahaffey, K. W.
    Cannon, C.
    Himmelmann, A.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. 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.
    Difference in causes of death between ticagrelor and clopidogrel in the PLATO trial2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no S1, p. 827-827Article in journal (Other academic)
  • 45.
    Varenhorst, Christoph
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alström, Ulrica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Braun, Oscar Ö
    Storey, Robert F
    Mahaffey, Kenneth W
    Bertilsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Cannon, Christopher P
    Scirica, Benjamin M
    Himmelmann, Anders
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, 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, 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.
    Causes of mortality with ticagrelor compared with clopidogrel in acute coronary syndromes2014In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 100, no 22, p. 1762-1769Article in journal (Refereed)
    Abstract [en]

    Objective

    To describe specific causes of death and evaluate whether bleeding events and infection contributed to mortality in all ticagrelor-treated and clopidogrel-treated patients with acute coronary syndromes.

    Methods

    In the PLATelet inhibition and patient Outcomes (PLATO) trial, ticagrelor significantly reduced rates of vascular and total death compared with clopidogrel. In the 905 patients who died postenrolment in the PLATO trial (n=18 624), reviewers, blinded to study treatment, subclassified direct causes of death and evaluated whether infection or bleeding events contributed to fatal events.

    Results

    Among vascular deaths, there were significantly fewer sudden deaths (63 (0.7%) vs 98 (1.1%), p<0.01) but no significant difference in deaths caused by acute myocardial infarction (179 (1.9%) vs 194 (2.1%), p=0.43) or heart failure (31 (0.3%) vs 42 (0.5%), p=0.20) with ticagrelor compared with clopidogrel. For non-vascular deaths, there was no difference between treatments in deaths directly caused by infection. Although, patients treated with ticagrelor were at lower risk for death where infection was either a direct cause or contributed to death (51 (0.5%) vs 76 (0.8%), HR 0.67 (0.47 to 0.95), p<0.05) but not for bleeding (42 (0.5%) vs 42 (0.5%), HR 0.99 (0.65 to 1.53), p=0.98).

    Conclusions

    In this post hoc analysis, ticagrelor compared with clopidogrel reduced total and cardiovascular mortality, which appeared to be mainly mediated by a reduction in sudden death. Importantly, bleeding causing or contributing to death did not differ between treatments.

    Clinical trial registration number

    NCT00391872 (http://www.clinicaltrial.gov).

  • 46.
    Varenhorst, Christoph
    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.
    Alström, Ulrica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Scirica, Benjamin M.
    Hogue, Charles W.
    Asenblad, Nils
    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.
    Storey, Robert F.
    Steg, Gabriel
    Horrow, Jay
    Mahaffey, Kenneth W.
    Becker, Richard C.
    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.
    Cannon, Christopher P.
    Brandrup-Wognsen, Gunnar
    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.
    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.
    Factors Contributing to the Lower Mortality With Ticagrelor Compared With Clopidogrel in Patients Undergoing Coronary Artery Bypass Surgery2012In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 60, no 17, p. 1623-1630Article in journal (Refereed)
    Abstract [en]

    Objectives This study investigated the differences in specific causes of post-coronary artery bypass graft surgery (CABG) deaths in the PLATO (Platelet Inhibition and Patient Outcomes) trial. Background In the PLATO trial, patients assigned to ticagrelor compared with clopidogrel and who underwent CABG had significantly lower total and cardiovascular mortality. Methods In the 1,261 patients with CABG performed within 7 days after stopping study drug, reviewers blinded to treatment assignment classified causes of death into subcategories of vascular and nonvascular, and specifically identified bleeding or infection events that either caused or subsequently contributed to death. Results Numerically more vascular deaths occurred in the clopidogrel versus the ticagrelor group related to myocardial infarction (14 vs. 10), heart failure (9 vs. 6), arrhythmia or sudden death (9 vs. 3), and bleeding, including hemorrhagic stroke (7 vs. 2). Clopidogrel was also associated with an excess of nonvascular deaths related to infection (8 vs. 2). Among factors directly causing or contributing to death, bleeding and infections were more common in the clopidogrel group compared with the ticagrelor group (infections: 16 vs. 6, p < 0.05, and bleeding: 27 vs. 9, p < 0.01, for clopidogrel and ticagrelor, respectively). Conclusions The mortality reduction with ticagrelor versus clopidogrel following CABG in the PLATO trial was associated with fewer deaths from cardiovascular, bleeding, and infection complications.

  • 47.
    Varenhorst, Christoph
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bodegard, J.
    AstraZeneca Nord Balt, Sodertalje, Sweden..
    Jerstrom, S.
    AstraZeneca Nord Balt, Sodertalje, Sweden..
    Akesson, J.
    AstraZeneca Nord Balt, Sodertalje, Sweden..
    Brorsson, H.
    Statisticon AB, Uppsala, Sweden..
    Alfredsson, J.
    Linkoping Univ, Dept Cardiol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Fac Hlth Sci, Linkoping, Sweden..
    Albertsson, P.
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Karlsson, J. E.
    Ryhov Cty Hosp, Dept Internal Medicin, Jonkoping, Sweden..
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Dept Med Sci, Cardiol, Uppsala, Sweden..
    Effects of interactive patient support with a smartphone app on drug adherence and lifestyle changes in myocardial infarction patients2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no 1 Supplement, p. 1202-1202Article in journal (Other academic)
  • 48.
    Varenhorst, Christoph
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Barratt, Bryan J.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Åkerblom, Axel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Becker, Richard C.
    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.
    Husted, Steen
    Steg, Ph. Gabriel
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Voora, Deepak
    Teng, Renli
    Storey, Robert F.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Effect of genetic variations on ticagrelor plasma levels and clinical outcomes2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no 29, p. 1901-1912Article in journal (Refereed)
    Abstract [en]

    Aims Ticagrelor, a direct-acting P2Y(12)-receptor antagonist, is rapidly absorbed and partly metabolized to the major metabolite AR-C124910XX (ARC). To identify single-nucleotide polymorphisms (SNPs) associated with pharmacokinetics of ticagrelor and clinical outcomes, we performed a genome-wide association study (GWAS) in patients treated with ticagrelor in the PLATO trial. Methods and results A two-stage design was used for the GWAS with discovery (discovery phase: n = 1812) and replication cohorts (replication phase: n = 1941). The steady-state area under the curve (AUCss) values, estimated by the population pharmacokinetic (PK) models, were log transformed and analysed on a genome-wide scale using linear regression. SNPs were analysed against clinical events using Cox-regression in 4990 patients. An SNP (rs113681054) in SLCO1B1 was associated with levels of ticagrelor (P = 1.1 x 10(-6)) and ARC (P = 4.6 x 10(-13)). This SNP is in linkage disequilibrium with a functional variant (rs4149056) that results in decreased OATP1B1 transporter activity. Ticagrelor levels were also associated with two independent SNPs (rs62471956, P = 7.7 x 10(-15) and rs56324128, P = 9.7 x 10(-12)) in the CYP3A4 region. Further, ARC levels were associated with rs61361928 (P = 3.0 x 10(-14)) in UGT2B7. At all loci, the effects were small. None of the identified SNPs that affected ticagrelor PK were associated with the primary composite outcome (cardiovascular death myocardial infarction, and stroke), non-CABG-related bleeds or investigator-reported dyspnoea. Conclusion In patients with ACS, ticagrelor pharmacokinetics is influenced by three genetic loci (SLCO1B1, UGT2B7, and CYP3A4). However, the modest genetic effects on ticagrelor plasma levels did not translate into any detectable effect on efficacy or safety during ticagrelor treatment.

  • 49.
    Varenhorst, Christoph
    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.
    Hasvold, Pal
    AstraZeneca Nord Baltic, Sodertalje, Sweden.;AstraZeneca R&D, Molndal, Sweden..
    Johansson, Saga
    AstraZeneca R&D, Molndal, Sweden..
    Janzon, Magnus
    Linkoping Univ, Dept Cardiol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Albertsson, Per
    Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden..
    Leosdottir, Margret
    Lund Univ, Dept Cardiol, Skane Univ Hosp, Malmo, Sweden..
    Hambraeus, Kristina
    Falun Cty Hosp, Falun, Sweden..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jernberg, Tomas
    Solna Karolinska Univ Hosp, Karolinska Inst, Dept Med, Sect Cardiol, Stockholm, Sweden..
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Culprit and Nonculprit Recurrent Ischemic Events in Patients With Myocardial Infarction: Data From SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies)2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 1, article id e007174Article in journal (Refereed)
    Abstract [en]

    Background-Long-term disease progression after myocardial infarction (MI) is inadequately understood. We evaluated the pattern and angiographic properties (culprit lesion [CL]/non-CL [NCL]) of recurrent MI (re-MI) in a large real-world patient population. Methods and Results-Our observational study used prospectively collected data in 108 615 patients with first-occurrence MI enrolled in the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) between July 1, 2006 and November 29, 2014. During follow-up (median, 3.2 years), recurrent hospitalization for MI occurred in 11 117 patients (10.2%). Of the patients who underwent coronary angiography for the index MI, a CL was identified in 44 332 patients. Of those patients, 3464 experienced an re-MI; the infarct originated from the NCL in 1243 patients and from the CL in 655 patients. In total, 1566 re-MIs were indeterminate events and could not be classified as NCL or CL re-MIs. The risk of re-MI within 8 years related to the NCL was 0.06 (95% confidence interval [CI], 0.05-0.06), compared with 0.03 (95% CI, 0.02-0.03) for the CL. There were no large differences in baseline characteristics of patients with subsequent NCL versus CL re-MIs. Independent predictors of NCL versus CL re-MI were multivessel disease (odds ratio, 2.29; 95% CI, 1.87-2.82), male sex (odds ratio, 1.36; 95% CI, 1.09-1.71), and a prolonged time between the index and re-MI (odds ratio, 1.16; 95% CI, 1.10-1.22). Conclusions-In a large cohort of patients with first-occurrence MI undergoing percutaneous coronary intervention, the risk of re-MI originating from a previously untreated lesion was twice higher than the risk of lesions originating from a previously stented lesion.

  • 50.
    Varenhorst, Christoph
    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. Uppsala Clin Res Ctr MTC, MTC, S-75237 Uppsala, Sweden.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala Clin Res Ctr MTC, MTC, S-75237 Uppsala, Sweden.
    Which antiplatelet agent for whom? Which patient populations benefit most from novel antiplatelet agents (ticagrelor, prasugrel)?2012In: Current Cardiology Reports, ISSN 1523-3782, E-ISSN 1534-3170, Vol. 14, no 4, p. 486-492Article in journal (Refereed)
    Abstract [en]

    Antiplatelet treatment is a cornerstone for patients with acute coronary syndromes treated invasively or conservatively to reduce the risk of early and late occurring ischemic complications and to improve survival. Compared to clopidogrel, the novel antiplatelet agents prasugrel and ticagrelor provide faster and more consistent inhibition of platelet aggregation and result in substantially improved clinical outcome in patients with acute coronary syndromes but also an increased bleeding risk. Therefore, balancing the rope between safety and efficacy of treatment is crucial for optimizing outcome. An understanding of the similarities but also differences in pharmacological effect, clinical trial design, and outcome is crucial for understanding which patient populations benefit the most from novel antiplatelet treatments. This review provides recommendations for their optimal use.

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