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  • 1. Bellavia, Andrea
    et al.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Orsini, Nicola
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Cannon, Christopher P
    Himmelmann, Anders
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Time-based measures of treatment effect: reassessment of ticagrelor and clopidogrel from the PLATO trial2017In: Open heart, ISSN 0168-2601, E-ISSN 2053-3624, Vol. 4, no 2, article id e000557Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

  • 2.
    Bjorck, Fredrik
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lip, Gregory Y. H.
    Univ Birmingham, Inst Cardiovasc Sci, Birmingham, W Midlands, England.;Aalborg Univ, Dept Clin Med, Aalborg Thrombosis Res Unit, Aalborg, Denmark..
    Wester, Per
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.;Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Svensson, Peter J.
    Lund Univ, Dept Coagulat Disorders, Malmo, Sweden..
    Sjalander, Anders
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Outcomes in a Warfarin-Treated Population With Atrial Fibrillation2016In: JAMA cardiology, ISSN 2380-6583, E-ISSN 2380-6591, Vol. 1, no 2, p. 172-180Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Vitamin K antagonist (eg, warfarin) use is nowadays challenged by the non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in atrial fibrillation (AF). NOAC studies were based on comparisons with warfarin arms with times in therapeutic range (TTRs) of 55.2% to 64.9%, making the results less credible in health care systems with higher TTRs. OBJECTIVES To evaluate the efficacy and safety of well-managed warfarin therapy in patients with nonvalvular AF, the risk of complications, especially intracranial bleeding, in patients with concomitant use of aspirin, and the impact of international normalized ratio (INR) control. DESIGN, SETTING, AND PARTICIPANTS A retrospective, multicenter cohort study based on Swedish registries, especially AuriculA, a quality register for AF and oral anticoagulation, was conducted. The register contains nationwide data, including that from specialized anticoagulation clinics and primary health care centers. A total of 40 449 patients starting warfarin therapy owing to nonvalvular AF during the study period were monitored until treatment cessation, death, or the end of the study. The study was conducted from January 1, 2006, to December 31, 2011, and data were analyzed between February 1 and November 15, 2015. Associating complications with risk factors and individual INR control, we evaluated the efficacy and safety of warfarin treatment in patients with concomitant aspirin therapy and those with no additional antiplatelet medications. EXPOSURES Use of warfarin with and without concomitant therapy with aspirin. MAIN OUTCOMES AND MEASURES Annual incidence of complications in association with individual TTR (iTTR), INR variability, and aspirin use and identification of factors indicating the probability of intracranial bleeding. RESULTS Of the 40 449 patients included in the study, 16 201 (40.0%) were women; mean (SD) age of the cohort was 72.5 (10.1) years, and the mean CHA(2)DS(2)-VASc (cardiac failure or dysfunction, hypertension, age >= 75 years [doubled], diabetes mellitus, stroke [doubled]-vascular disease, age 65-74 years, and sex category [female]) score was 3.3 at baseline. The annual incidence, reported as percentage (95% CI) of all-cause mortality was 2.19% (2.07-2.31) and, for intracranial bleeding, 0.44%(0.39-0.49). Patients receiving concomitant aspirin had annual rates of any major bleeding of 3.07%(2.70-3.44) and thromboembolism of 4.90% (4.43-5.37), and those with renal failure were at higher risk of intracranial bleeding (hazard ratio, 2.25; 95% CI, 1.32-3.82). Annual rates of any major bleeding and any thromboembolism in iTTR less than 70% were 3.81% (3.51-4.11) and 4.41% (4.09-4.73), respectively, and, in high INR variability, were 3.04%(2.85-3.24) and 3.48% (3.27-3.69), respectively. For patients with iTTR 70% or greater, the level of INR variability did not alter event rates. CONCLUSIONS AND RELEVANCE Well-managed warfarin therapy is associated with a low risk of complications and is still a valid alternative for prophylaxis of AF-associated stroke. Therapy should be closely monitored for patients with renal failure, concomitant aspirin use, and poor INR control.

  • 3.
    Bjorck, Fredrik
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, Sundsvall, Sweden..
    Sanden, Per
    Umea Univ, Dept Publ Hlth & Clin Med, Sundsvall, Sweden..
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Svensson, Peter J.
    Lund Univ, Dept Coagulat Disorders, Malmo, Sweden..
    Sjalander, Anders
    Umea Univ, Dept Publ Hlth & Clin Med, Sundsvall, Sweden..
    Warfarin treatment quality is consistently high in both anticoagulation clinics and primary care setting in Sweden2015In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 136, no 2, p. 216-220Article in journal (Refereed)
    Abstract [en]

    Background: Warfarin treatment in Sweden holds a high standard with time in therapeutic range (TTR) over 75%. Internationally, specialized anticoagulation clinics (ACC) have shown higher TTR compared to primary health care centres (PHCC). Objectives: To compare warfarin treatment quality in Sweden for ACC versus PHCC, thereby clarifying whether centralization is for the better. Patients/methods: In total 77.058 patients corresponding to 217.058 treatment years with warfarin in the Swedish national quality register AuriculA from 1. Jan 2006 to 31. Dec 2011. Information regarding TTR was calculated from AuriculA, while patient characteristics and complications were retrieved from the Swedish National Patient Register. Results: Of the 100.554 treatment periods examined, 78.7% were monitored at ACC. Mean TTR for INR 2-3 for all patients irrespective of intended target range was 76.5% with an annual risk of bleeding or thrombotic events of 2.24% and 2.66%, respectively. TTR was significantly higher in PHCC compared to ACC (79.6% vs. 75.7%, p < 0.001), with no significant difference in overall risk of complications. Treatment periods for atrial fibrillation, except intended direct current conversion, showed similar results between ACC and PHCC without significant difference in annual risk of bleeding (2.50% vs. 2.51%) or thrombosis (3.09% vs. 3.16%). After propensity score matching there was still no significant difference in complication risk found. Conclusions: Warfarin treatment quality is consistently high in both ACC and PHCC when monitored through AuriculA in Sweden, both measured as TTR and as risk of complications. In this setting, centralized warfarin monitoring is not likely to improve the results.

  • 4.
    Björck, Fredrik
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, S-90187 Umea, Sweden..
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Svensson, Peter J.
    Lund Univ, Dept Coagulat Disorders, Malmö, Sweden..
    Själander, Anders
    Umea Univ, Dept Publ Hlth & Clin Med, S-90187 Umea, Sweden..
    Warfarin persistence among stroke patients with atrial fibrillation2015In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 136, no 4, p. 744-748Article in journal (Refereed)
    Abstract [en]

    Introduction: Warfarin treatment discontinuation is significant among patients with atrial fibrillation (AF). For AF patients with stroke a warfarin persistence rate of 0.45 after 2 years has previously been reported. No consistent predictors for discontinuation have been established. Aims: Evaluation of warfarin persistence and variables associated with discontinuation, in a large Swedish cohort with unselected stroke/TIA patients with AF treated with warfarin. Materials and methods: 4 583 patients with stroke/TIA and AF in the Swedish National Patient Register (NPR), from 1. Jan 2006 to 31. Dec 2011, were matched with the Swedish national quality register AuriculA. They were followed until treatment cessation, death or end of study. Baseline characteristics and CHA(2)DS(2)VASc score were retrieved from NPR. Treatment-time was retrieved from AuriculA. Results: Overall proportion of warfarin persistence was 0.78 (95% confidence interval (CI) 0.76 to 0.80) after one year, 0.69 (95% CI 0.67 to 0.71) after 2 years and 0.47 (95% CI 0.43 to 0.51) after 5 years. Variables clearly associated with higher discontinuation were dementia (hazard ratio (HR) 2.22, CI 1.51-3.27) and alcohol abuse (HR 1.66, CI 1.19-2.33). Chronic obstructive pulmonary disease (COPD), cancer and chronic heart failure (CHF) were each associated with over 20% increased risk of treatment discontinuation. Higher CHA(2)DS(2)VASc score and start-age lead to lower persistence (p < 0.001). Conclusions: Persistence to warfarin in unselected stroke/TIA patients with AF is in Sweden greater than previously reported. Lower persistence is found among patients with high treatment start-age, incidence of dementia, alcohol abuse, cancer, CHF, COPD and/or high CHA(2)DS(2)VASc score.

  • 5. Grzymala-Lubanski, B.
    et al.
    Själander, S.
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Svensson, P. J.
    Själander, A.
    Computer aided warfarin dosing in the Swedish national quality registry AuriculA - Algorithmic suggestions are performing better than manually changed doses2013In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 131, no 2, p. 130-134Article in journal (Refereed)
    Abstract [en]

    Introduction Warfarin treatment with a high time in therapeutic range (TTR) is correlated to fewer complications. The TTR in Sweden is generally high but varies partly depending on local expertise and traditions. A dosing algorithm could minimize variations and increase treatment quality. Here we evaluate the performance of a computerized dosing algorithm. Materials and methods 53.779 warfarin treated patients from 125 centers using the Swedish national quality registry AuriculA. If certain criteria are met, the algorithm gives one of seven possible dose suggestions, which can be unchanged, decreased or increased weekly dose by 5, 10 or 15%. The outcome evaluated by the resulting INR value was compared between dose suggestions arising from the algorithm that were accepted and those that were manually changed. There were no randomization, and outcomes were retrospectively analyzed. Results Both the algorithm-based and the manually changed doses had worse outcome if only two instead of three previous INR values were available. The algorithm suggestions were superior to manual dosing regarding percent samples within the target range 2-3 (hit-rate) or deviation from INR 2.5 (mean error). Of the seven possible outcomes from the algorithm, six were significantly superior and one equal to the manually changed doses when three previous INR:s were present. Conclusions The algorithm-based dosing suggestions show better outcome in most cases. This can make dosing of warfarin easier and more efficient. There are however cases where manual dosing fares better. Here the algorithm will be improved to further enhance its dosing performance in the future.

  • 6.
    Grzymala-Lubanski, Bartosz
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Svensson, Peter J.
    Lund Univ, Dept Coagulat Disorders, Malmo, Sweden..
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jeppsson, Anders
    Sahlgrens Univ Hosp, Dept Cardiothorac Surg, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden..
    Själänder, Anders
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Warfarin treatment quality and prognosis in patients with mechanical heart valve prosthesis2017In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 103, no 3, p. 198-203Article in journal (Refereed)
    Abstract [en]

    Objectives To study the impact of time in therapeutic range (TTR) and international normalised ratio (INR) variability on the risk of thromboembolic events, major bleeding complications and death after mechanical heart valve (MHV) implantation. Additionally, the importance of different target INR levels was elucidated. Methods A retrospective, non-randomised multicentre cohort study including all patients with mechanical heart valve (MVH) prosthesis registered in the Swedish National Quality Registry Auricula from 2006 to 2011. Data were merged with the Swedish National Patient Registry, SWEDEHEART and Cause of Death Registry. Results In total 4687 ordination periods, corresponding to 18 022 patient-years on warfarin, were included. High INR variability (above mean >= 0.40) or lower TTR (<= 70%) was associated with a higher risk of bleeding (rate per 100 years 4.33 (95% CI 3.87 to 4.82) vs 2.08 (1.78 to 2.41); HR 2.15 (1.75 to 2.61) and 5.13 (4.51 to 5.82) vs 2.30 (2.03 to 2.60); HR 2.43 (2.02 to 2.89)), respectively. High variability and low TTR combined was associated with an even higher risk of bleedings (rate per 100 years 4.12 (95% CI 3.68 to 4.51) vs 2.02 (1.71 to 2.30); HR 2.16 (1.71 to 2.58) and 4.99 (4.38 to 5.52) vs 2.36 (2.06 to 2.60); HR 2.38 (2.05 to 2.85)) compared with the best group. Higher treatment intensity (mean INR 2.8-3.2 vs 2.2-2.7) was associated with higher rate of bleedings (2.92 (2.39 to 3.47) vs 2.48 (2.21 to 2.77); HR 1.29 (1.06 to 1.58)), death (3.36 (2.79 to 4.02) vs 1.89 (1.64 to 2.17), HR 1.65 (1.31 to 2.06)) and complications in total (6.61 (5.74 to 7.46) vs 5.65 (5.20 to 6.06); HR 1.24 (1.06 to 1.41)) after adjustment for MHV position, age and comorbidity. Conclusions A high warfarin treatment quality improves outcome after MHV implantation, both measured with TTR and INR variability. No benefit was found with higher treatment intensity (mean INR 2.8-3.2 vs 2.2-2.7).

  • 7.
    Hellström, Vivan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Enström, Ylva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Nyberg, Filippa
    Risk Factors for De Novo Squamous Cell Carcinoma Development in Renal Transplant Recipients with a Previous Squamous Cell Carcinoma.2017In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 97, no 6, p. 751-753Article in journal (Refereed)
  • 8.
    James, Stefan K.
    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.
    Bellavia, Andrea
    Orsini, Nicola
    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.
    Cannon, Christopher
    Harrington, Robert
    Himmelmann, Anders
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Time Based Measures Of Treatment Effect: Reassessment Of Ticagrelor Versus Clopidogrel In The Plato Study2016In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 67, no 13, p. 548-548Article in journal (Other academic)
  • 9.
    Johnston, Nina
    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.
    Jönelid, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Christersson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Kero, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Schenck-Gustafsson, Karin
    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.
    Effect of Gender on Patients With ST-Elevation and Non-ST-Elevation Myocardial Infarction Without Obstructive Coronary Artery Disease2015In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 115, no 12, p. 1661-1666Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to compare the prognoses of patients with ST-segment elevation myocardial infarction (STEMI) and those with non-ST-segment elevation myocardial infarction (NSTEMI) without obstructive coronary artery disease (CAD) and the risk associated with gender for future cardiovascular events. The study population was selected from 95,849 patients who underwent coronary angiography for myocardial infarction from 2005 to 2010 and registered in the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Outcome analyses, including all-cause death, myocardial infarction, congestive heart failure, stroke, and revascularization, were performed in 2,268 patients with STEMI and 10,904 with NSTEMI without obstructive CAD (<50% stenosis). Hazard ratios and 95% confidence intervals comparing women with men were calculated for events, adjusting for cardiovascular risk factors and age. Nonobstructive CAD was found in 7% of patients with STEMI (6% men, 10% women) and in 17% of those with NSTEMI (11% men, 28% women). During a median follow-up of 2.6 years, 8% of patients with STEMI and 5% of those with NSTEMI died. Gender-associated differences in risk were observed in patients with NSTEMI, with adjusted hazard ratios lower in women than men for mortality (hazard ratio 0.90, 95% confidence interval 0.50 to 0.73) and congestive heart failure (hazard ratio 0.61, 95% confidence interval 0.52 to 0.72). In the 2 groups, women underwent less revascularization. In conclusion, nonobstructive CAD was more common in patients with NSTEMI than those with STEMI, as well as in women compared with men. Long-term mortality in patients with nonobstructive CAD was higher after STEMI than NSTEMI. The gender differences in outcomes suggest gender differences in the underlying pathogenesis of myocardial infarction without obstructive CAD.

  • 10.
    Jolly, Sanjit S.
    et al.
    McMaster Univ, Hamilton, ON, Canada.;Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada..
    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.
    Dzavik, Vladimir
    Univ Hlth Network, Peter Munk Cardiac Ctr, Toronto, ON, Canada..
    Cairns, John A.
    Univ British Columbia, Vancouver, BC, Canada..
    Mahmoud, Karim D.
    Erasmus MC, Ctr Thorax, Dept Cardiol, Rotterdam, Netherlands..
    Zijlstra, Felix
    Erasmus MC, Ctr Thorax, Dept Cardiol, Rotterdam, Netherlands..
    Yusuf, Salim
    McMaster Univ, Hamilton, ON, Canada.;Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Olivecrona, Göran K.
    Lund Univ, Skane Univ Hosp Lund, Lund, Sweden..
    Renlund, Henrik
    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.
    Gao, Peggy
    McMaster Univ, Hamilton, ON, Canada.;Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada..
    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.
    Alazzoni, Ashraf
    McMaster Univ, Hamilton, ON, Canada.;Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Kedev, Sasko
    Sts Cyril & Methodius Univ, Univ Clin Cardiol, Skopje, Macedonia..
    Stankovic, Goran
    Univ Belgrade, Fac Med, Clin Ctr Serbia, Belgrade, Serbia.;Univ Belgrade, Fac Med, Dept Cardiol, Belgrade, Serbia..
    Meeks, Brandi
    McMaster Univ, Hamilton, ON, Canada.;Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Frobert, Ole
    Univ Orebro, Fac Hlth, Dept Cardiol, Orebro, Sweden..
    Thrombus Aspiration in ST-Segment-Elevation Myocardial Infarction An Individual Patient Meta-Analysis: Thrombectomy Trialists Collaboration2017In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 135, no 2, p. 143-+Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Thrombus aspiration during percutaneous coronary intervention (PCI) for the treatment of ST-segment-elevation myocardial infarction (STEMI) has been widely used; however, recent trials have questioned its value and safety. In this meta-analysis, we, the trial investigators, aimed to pool the individual patient data from these trials to determine the benefits and risks of thrombus aspiration during PCI in patients with ST-segment-elevation myocardial infarction. METHODS: Included were large (n >= 1000), randomized, controlled trials comparing manual thrombectomy and PCI alone in patients with ST-segment-elevation myocardial infarction. Individual patient data were provided by the leadership of each trial. The prespecified primary efficacy outcome was cardiovascular mortality within 30 days, and the primary safety outcome was stroke or transient ischemic attack within 30 days. RESULTS: The 3 eligible randomized trials (TAPAS [Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction], TASTE [Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia], and TOTAL [Trial of Routine Aspiration Thrombectomy With PCI Versus PCI Alone in Patients With STEMI]) enrolled 19 047 patients, of whom 18 306 underwent PCI and were included in the primary analysis. Cardiovascular death at 30 days occurred in 221 of 9155 patients (2.4%) randomized to thrombus aspiration and 262 of 9151 (2.9%) randomized to PCI alone (hazard ratio, 0.84; 95% confidence interval, 0.70-1.01; P=0.06). Stroke or transient ischemic attack occurred in 66 (0.8%) randomized to thrombus aspiration and 46 (0.5%) randomized to PCI alone (odds ratio, 1.43; 95% confidence interval, 0.98-2.10; P=0.06). There were no significant differences in recurrent myocardial infarction, stent thrombosis, heart failure, or target vessel revascularization. In the subgroup with high thrombus burden (TIMI [Thrombolysis in Myocardial Infarction] thrombus grade >= 3), thrombus aspiration was associated with fewer cardiovascular deaths (170 [2.5%] versus 205 [3.1%]; hazard ratio, 0.80; 95% confidence interval, 0.65-0.98; P=0.03) and with more strokes or transient ischemic attacks (55 [0.9%] versus 34 [0.5%]; odds ratio, 1.56; 95% confidence interval, 1.02-2.42, P=0.04). However, the interaction P values were 0.32 and 0.34, respectively. CONCLUSIONS: Routine thrombus aspiration during PCI for ST-segment-elevation myocardial infarction did not improve clinical outcomes. In the high thrombus burden group, the trends toward reduced cardiovascular death and increased stroke or transient ischemic attack provide a rationale for future trials of improved thrombus aspiration technologies in this high-risk subgroup.

  • 11.
    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.

  • 12.
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics, Mathematical Statistics.
    First-passage percolation on ladder-like graphs with heterogeneous exponential times.2011Report (Other academic)
    Abstract [en]

    We determine the asymptotic speed of the first-passage percolation process on some ladder-like graphs (or width-2 stretches) when the times associated with different edges are independent and exponentially distributed but not necessarily all with the same mean. The method uses a particular Markov chain associated with the first-passage percolation process and properties of its stationary distribution.

  • 13.
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics, Mathematical Statistics.
    First-passage percolation with exponential times on a ladder2008Report (Other (popular science, discussion, etc.))
  • 14.
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics, Mathematical Statistics.
    Generalized Pólya Urns via Stochastic Approximation2009Licentiate thesis, monograph (Other academic)
  • 15.
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics, Mathematical Statistics.
    Limit theorems for stochastic approximation algorithms.2011Report (Other academic)
    Abstract [en]

    We prove a central limit theorem applicable to one dimensional stochastic approximation algorithms that converge to a point where the error terms of the algorithm do not vanish. We show how this applies to a certain class of these algorithms that in particular covers a generalized Pólya urn model, which is also discussed.  In addition, we  show how to scale these algorithms in some cases where we cannot determine the limiting distribution but expect it to be non-normal.

  • 16.
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics, Mathematical Statistics.
    Recursive Methods in Urn Models and First-Passage Percolation2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This PhD thesis consists of a summary and four papers which deal with stochastic approximation algorithms and first-passage percolation.

    Paper I deals with the a.s. limiting properties of bounded stochastic approximation algorithms in relation to the equilibrium points of the drift function. Applications are given to some generalized Pólya urn processes.

    Paper II continues the work of Paper I and investigates under what circumstances one gets asymptotic normality from a properly scaled algorithm. The algorithms are shown to converge in some other circumstances, although the limiting distribution is not identified.

    Paper III deals with the asymptotic speed of first-passage percolation on a graph called the ladder when the times associated to the edges are independent, exponentially distributed with the same intensity.

    Paper IV generalizes the work of Paper III in allowing more edges in the graph as well as not having all intensities equal.

    List of papers
    1. Generalized Pólya Urns via Stochastic Approximation
    Open this publication in new window or tab >>Generalized Pólya Urns via Stochastic Approximation
    2009 (English)Licentiate thesis, monograph (Other academic)
    Place, publisher, year, edition, pages
    Uppsala: Department of Mathematics, Uppsala University, 2009
    Series
    U.U.D.M. report / Uppsala University, Department of Mathematics, ISSN 1101-3591 ; 2009:7
    Keywords
    stochastic approximation, unstable equilibrium, stable equilibrium, touchpoint, generalized pólya urns
    National Category
    Mathematics
    Research subject
    Mathematics
    Identifiers
    urn:nbn:se:uu:diva-106522 (URN)
    Presentation
    64119, Ångström Lab., Uppsala (Swedish)
    Opponent
    Supervisors
    Available from: 2009-06-25 Created: 2009-06-25 Last updated: 2012-07-26Bibliographically approved
    2. Limit theorems for stochastic approximation algorithms.
    Open this publication in new window or tab >>Limit theorems for stochastic approximation algorithms.
    2011 (English)Report (Other academic)
    Abstract [en]

    We prove a central limit theorem applicable to one dimensional stochastic approximation algorithms that converge to a point where the error terms of the algorithm do not vanish. We show how this applies to a certain class of these algorithms that in particular covers a generalized Pólya urn model, which is also discussed.  In addition, we  show how to scale these algorithms in some cases where we cannot determine the limiting distribution but expect it to be non-normal.

    Publisher
    p. 26
    Series
    U.U.D.M ; 2011:6
    Keywords
    stochastic approximation algorithms, central limit theorem, generalized Polya urn
    National Category
    Probability Theory and Statistics
    Research subject
    Mathematical Statistics
    Identifiers
    urn:nbn:se:uu:diva-145343 (URN)
    Available from: 2011-02-09 Created: 2011-02-08 Last updated: 2011-02-14Bibliographically approved
    3. First-Passage Percolation with Exponential Times on a Ladder
    Open this publication in new window or tab >>First-Passage Percolation with Exponential Times on a Ladder
    2010 (English)In: Combinatorics, probability & computing, ISSN 0963-5483, E-ISSN 1469-2163, Vol. 19, no 4, p. 593-601Article in journal (Refereed) Published
    Abstract [en]

    We consider first-passage percolation on a ladder, i.e., the graph N x {0, 1}, where nodes at distance 1 are joined by an edge, and the times are exponentially i.i.d. with mean 1. We find an appropriate Markov chain to calculate an explicit expression for the time constant whose numerical value is approximate to 0.6827. This time constant is the long-term average inverse speed of the process. We also calculate the average residual time.

    National Category
    Mathematics
    Identifiers
    urn:nbn:se:uu:diva-136164 (URN)10.1017/S0963548310000052 (DOI)000279038700007 ()
    Available from: 2010-12-10 Created: 2010-12-10 Last updated: 2017-12-11Bibliographically approved
    4. First-passage percolation on ladder-like graphs with heterogeneous exponential times.
    Open this publication in new window or tab >>First-passage percolation on ladder-like graphs with heterogeneous exponential times.
    2011 (English)Report (Other academic)
    Abstract [en]

    We determine the asymptotic speed of the first-passage percolation process on some ladder-like graphs (or width-2 stretches) when the times associated with different edges are independent and exponentially distributed but not necessarily all with the same mean. The method uses a particular Markov chain associated with the first-passage percolation process and properties of its stationary distribution.

    Publisher
    p. 25
    Series
    U.U.D.M ; 2011:5
    Keywords
    first-passage percolation, rate of percolation
    National Category
    Probability Theory and Statistics
    Research subject
    Mathematical Statistics
    Identifiers
    urn:nbn:se:uu:diva-145340 (URN)
    Available from: 2011-02-09 Created: 2011-02-08 Last updated: 2011-02-14Bibliographically approved
  • 17.
    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.

  • 18.
    Sanden, Per
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, Sundsvall, Sweden..
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Svensson, Peter J.
    Lund Univ, Dept Coagulat Disorders, Malmo, Sweden..
    Sjalander, Anders
    Umea Univ, Dept Publ Hlth & Clin Med, Sundsvall, Sweden..
    Bleeding complications and mortality in warfarin-treated VTE patients, dependence of INR variability and iTTR2017In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 117, no 1, p. 27-32Article in journal (Refereed)
    Abstract [en]

    High quality of warfarin treatment is important to prevent recurrence of venous thromboembolism (VTE) without bleeding complications. The aim of this study was to examine the effect of individual time in therapeutic range (iTTR) and International Normalised Ratio (INR) variability on bleeding risk and mortality in a large cohort of well managed patients with warfarin due to VTE. A cohort of 16612 patients corresponding to 19502 treatment periods with warfarin due to VTE between January 1, 2006 and December 31, 2011 was retrieved from the Swedish national quality register AuriculA and matched with the Swedish National Patient Register for bleeding complications and background characteristics and the Cause of death register for occurrence and date of death. The rate of bleeding was 1.79 (confidence interval (CI) 95 % 1.66-1.93) per 100 treatment years among all patients. Those with poor warfarin treatment quality had a higher rate of clinically relevant bleeding, both when measured as iTTR below 70%, 2.91 (CI 95% 2.61-3.21) or as INR variability over the mean value 0.85, 2.61 (CI 95% 2.36-2.86). Among those with both high INR variability and low iTTR the risk of clinically relevant bleeding was clearly increased hazard ratio (HR) 3.47 (CI 95 % 2.89-4.17). A similar result was found for all-cause mortality with a HR of 3.67 (CI 95 % 3.02-4.47). Both a low iTTR and a high INR variability increase the risk of bleeding complications or mortality. When combining the two treatment quality indicators patients at particular high risk of bleeding or death can be identified.

  • 19.
    Sanden, Per
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, Sundsvall, Sweden..
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Svensson, Peter J.
    Lund Univ, Dept Coagulat Disorders, Malmo, Sweden..
    Sjalander, Anders
    Umea Univ, Dept Publ Hlth & Clin Med, Sundsvall, Sweden..
    Warfarin treatment complications do not correlate to cTTR when above 70%2015In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 136, no 6, p. 1185-1189Article in journal (Refereed)
    Abstract [en]

    Background: The mean time in target range for each centre, cTTR, has previously been shown to correlate to the rate of complications in poorly managed warfarin treatment. However less is known about the correlation when warfarin treatment is well managed. Objectives: The aim of this study was to examine the correlation between cTTR and the rate of complications in a real life setting with cTTR above 70%, with focus on patients with warfarin due to atrial fibrillation or secondary prevention of a VTE. Patients/methods: In total 66,605 patients with 89,293 treatment periods, corresponding to 179,624 treatment years, with warfarin treatment due to VTE or AF between January 1st 2006 and December 31th 2011, was retrieved from the national quality register AuriculA. The cohort was matched with the National Patient Register in Sweden for complications and background characteristics. Results: We found 172 centres and 68,797 treatment periods for AF and 166 centres and 20,496 treatment periods for VTE. Over 90% of the patients had a target range between INR 2-3. We found no correlation between increasing cTTR and reduction in the rate of complications for the AF patients. However, for VTE patients we saw a correlation between increasing cTTR and a reduced complication rate. Conclusions: Our results show that at very high cTTR levels, above 70%, further improvements in cTTR do not correlate to less treatment complications at least for patients with AF.

  • 20.
    Sandén, Per
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, Sundsvall, Sweden..
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Svensson, Peter J.
    Lund Univ, Dept Coagulat Disorders, Malmo, Sweden..
    Sjalander, Anders
    Umea Univ, Dept Publ Hlth & Clin Med, Sundsvall, Sweden..
    Bleeding complications in venous thrombosis patients on well-managed warfarin2016In: Journal of Thrombosis and Thrombolysis, ISSN 0929-5305, E-ISSN 1573-742X, Vol. 41, no 2, p. 351-358Article in journal (Refereed)
    Abstract [en]

    Anticoagulation treatment is effective in preventing both death and recurrence in patients with venous thromboembolism (VTE), but at the same time confers a substantial risk of bleeding complications. The aim of this study was to examine the rate of and predictors for bleeding complications in VTE patients on warfarin with high treatment quality. In total 13,859 patients on warfarin for VTE between January 1st 2006 and December 31th 2011 were retrieved from the national quality register Auricula. The cohort was matched with the Swedish National Patient Register for complications and background characteristics, the Cause of Death Register for date and cause of death and the Swedish Prescribed Drug Register for retrieved medication. The rate of major bleeding was 2.36 per 100 treatment years, increasing with age from 1.25 to 4.33 for those under 60 or over 80 years of age, respectively. Factors found to independently increase the risk of bleeding complications were increasing age HR 1.02, cardiac failure HR 1.39, Chronic pulmonary disease HR 1.41, alcohol abuse HR 3.33, anaemia HR 1.75, hypertension HR 1.29 and a history of major bleeding HR 1.69. Warfarin as treatment for VTE is safe with a low rate of bleeding complications at least for the younger patient. In an era of NOAK, warfarin has a comparable safety profile among VTE patients and is still a valid treatment option.

  • 21. Sjogren, Vilhelm
    et al.
    Grzymala-Lubanski, Bartosz
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Friberg, Leif
    Lip, Gregory Y. H.
    Svensson, Peter J.
    Sjalander, Anders
    Safety and efficacy of well managed warfarin: A report from the Swedish quality register Auricula2015In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 113, no 6, p. 1370-1377Article in journal (Refereed)
    Abstract [en]

    The safety and efficacy of warfarin in a large, unselected cohort of warfarin-treated patients with high quality of care is comparable to that reported for non-vitamin K antagonists. Warfarin is commonly used for stroke prevention in atrial fibrillation, as well as for treatment and prevention of venous thromboembolism. While reducing risk of thrombotic/embolic incidents, warfarin increases the risk of bleeding. The aim of this study was to elucidate risks of bleeding and thromboembolism for patients on warfarin treatment in a large, unselected cohort with rigorously controlled treatment. This was a retrospective, registry-based study, covering all patients treated with warfarin in the Swedish national anticoagulation register Auricula, which records both primary and specialised care. The study included 77,423 unselected patients with 100,952 treatment periods of warfarin, constituting 217,804 treatment years. Study period was January 1, 2006 to December 31, 2011. Atrial fibrillation was the most common indication (68%). The mean time in therapeutic range of the international normalised ratio (INR) 2.0-3.0 was 76.5%. The annual incidence of I severe bleeding was 2.24% and of thromboembolism 2.65%. The incidence of intracranial bleeding was 0.37% per treatment year in the whole population, and 0.38% among patients with atrial fibrillation. In conclusion, warfarin treatment where patients spend a high proportion of time in the therapeutic range is safe and effective, and will continue to be a valid treatment option in the era of newer oral anticoagulants.

  • 22.
    Sjögren, Vilhelm
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Byström, Björn
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Svensson, Peter J.
    Lund Univ, Dept Translat Med, Clin Coagulat Res Unit, Skane Univ Hosp, Malmo, Sweden..
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Norrving, Bo
    Lund Hosp, Dept Clin Sci Lund, Neurol, Skane Univ Hosp, Lund, Sweden..
    Själander, Anders
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Non-vitamin K oral anticoagulants are non-inferior for stroke prevention but cause fewer major bleedings than well-managed warfarin: A retrospective register study2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 7, article id e0181000Article in journal (Refereed)
    Abstract [en]

    Background For patients with atrial fibrillation, non-vitamin K oral anticoagulants, or NOACs (dabigatran, rivaroxaban, edoxaban, and apixaban) have been proven non-inferior or superior to warfarin in preventing stroke and systemic embolism, and in risk of haemorrhage. In the pivotal NOAC studies, quality of warfarin treatment was poor with mean time in therapeutic range (TTR) 55-65%, compared with >= 70% in Swedish clinical practice. Methods We compared NOACs (as a group) to warfarin in non-valvular atrial fibrillation, studying all 12,694 patients starting NOAC treatment within the Swedish clinical register and dosing system Auricula, from July 1, 2011 to December 31, 2014, and matching them to 36,317 patients starting warfarin using propensity scoring. Endpoints were thromboembolic events and major bleedings that were fatal or required hospital care. Outcome data were collected from validated Swedish hospital administrative and clinical registers. Results Mean age was 72.2 vs 72.3 years, proportion of males 58.2% vs 57.0%, and mean follow-up time 299 vs 283 days for NOACs and warfarin. Distribution of NOACs was: dabigatran 40.3%, rivaroxaban 31.2%, and apixaban 28.5%. Mean TTR was 70%. There were no significant differences in rates of thromboembolic/thrombotic events or gastrointestinal bleeding. NOAC treated patients had lower rates of major bleeding overall, hazard ratio 0.78 (95% confidence interval 0.67-0.92), intracranial bleeding 0.59 (0.40-0.87), haemorrhagic stroke 0.49 (0.28-0.86), and other major bleeding 0.71 (0.57-0.89). Conclusion For patients with atrial fibrillation, NOACs are as effective for stroke prevention as well-managed warfarin but cause fewer major bleedings.

  • 23.
    Sjögren, Vilhelm
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Grzymala-Lubanski, Bartosz
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Svensson, Peter J.
    Lund Univ, Skane Univ Hosp, Clin Coagulat Res Unit, Dept Translat Med, Malmo, Sweden..
    Själander, Anders
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Safety and Efficacy of Bridging With Low-Molecular-Weight Heparin During Temporary Interruptions of Warfarin: A Register-Based Cohort Study2017In: Clinical and applied thrombosis/hemostasis, ISSN 1076-0296, E-ISSN 1938-2723, Vol. 23, no 8, p. 961-966Article in journal (Refereed)
    Abstract [en]

    Low-molecular-weight heparin (LMWH) is often recommended as a bridging therapy during temporary interruptions in warfarin treatment, despite lack of evidence. The aim of this study was to see whether we could find benefit from LMWH bridging. We studied all planned interruptions of warfarin within the Swedish anticoagulation register Auricula during 2006 to 2011. Low-molecular-weight heparin bridging was compared to nonbridging (control) after propensity score matching. Complications were identified in national clinical registers for 30 days following warfarin cessation, and defined as all-cause mortality, bleeding (intracranial, gastrointestinal, or other), or thrombosis (ischemic stroke or systemic embolism, venous thromboembolism, or myocardial infarction) that was fatal or required hospital care. Of the 14 556 identified warfarin interruptions, 12 659 with a known medical background had a mean age of 69 years, 61% were males, mean CHADS(2) (1 point for each of congestive heart failure, hypertension, age 75 years, diabetes, and 2 points for stroke or transient ischemic attack) score was 1.7, and CHA(2)DS(2)-VASc score was 3.4. The total number of LMWH bridgings was 7021. Major indications for anticoagulation were mechanical heart valve prostheses 4331, atrial fibrillation 1097, and venous thromboembolism 1331. Bridging patients had a higher rate of thrombotic events overall. Total risk of any complication did not differ significantly between bridging (1.5%) and nonbridging (1.2%). Regardless of indication for warfarin treatment, we found no benefit from bridging. The type of procedure prompting bridging was not known, and the likely reason for the observed higher risk of thrombosis with LMWH bridging is that low-risk procedures more often meant no bridging. Results from randomized trials are needed, especially for patients with mechanical heart valves.

  • 24.
    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)
  • 25.
    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.
    Åkerblom, Axel
    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.
    Kunadian, V.
    Newcastle Univ, Fac Med Sci, Newcastle Upon Tyne, Tyne & Wear, England..
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Steg, P. G.
    Hop Bichat Claude Bernard, Dept Hosp Univ FIRE, Paris, France..
    Katus, H. A.
    Univ Klinikum Heidelberg, Med Klin, Heidelberg, Germany..
    Himmelmann, A.
    AstraZeneca Res & Dev, Gothenburg, Sweden..
    Aylward, P.
    Flinders Univ S Australia, South Australian Hlth & Med Res Inst, Adelaide, SA, Australia.;Med Ctr, Adelaide, SA, Australia..
    Maurer, G.
    Med Univ Vienna, Vienna, Austria..
    Storey, R. F.
    Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England..
    Armstrong, P. W.
    Univ Alberta, Canadian VIGOUR Ctr, Edmonton, AB, Canada..
    Gibson, M.
    Harvard Med Sch, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Successful reperfusion is associated with lower levels of markers of myocardial damage and dysfunction in ST-elevation but not in non-ST-elevation myocardial infarction: insights from the PLATO trial2016In: EUROPEAN HEART JOURNAL, ISSN 0195-668X, Vol. 37, p. 1282-1283Article in journal (Refereed)
1 - 25 of 25
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