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  • 1.
    Björck, Fredrik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ek, Agnes
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Johansson, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Warfarin persistence among atrial fibrillation patients – why is treatment ended?2016Ingår i: Cardiovascular Therapeutics, ISSN 1755-5914, Vol. 34, nr 6, s. 468-474Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and Aim

    Warfarin treatment discontinuation is significant among patients with atrial fibrillation (AF). Studies mainly focused on whether the proportion of warfarin persistence and discontinuationare clinically appropriate are absent. This study evaluates warfarin persistence with focus on predictors for, and reasons to, warfarin discontinuation in AF patients.

    Methods

    From the national quality register AuriculA, all AF patients in Sundsvall, Sweden, on warfarin treatment on January first, 2010 were included. These 478 patients were followed until discontinuation or study-stop December 31, 2013. By going through each patient’s medical record risk factors for thromboembolism, bleeding and causes of discontinuation were obtained.

    Results

    Proportion of warfarin persistence was 0.91 (95% confidence interval (CI) 0.89 to 0.93) after one year and 0.73 (95% CI 0.69 to 0.77) after four years. Previous intracranial bleeding, excessive alcohol use, anemia and pulmonary or peripheral emboli were each associated with over two times higher risk of discontinuation (hazard ratio (HR) 5.66, CI 2.23-14.36, HR 2.54, CI 1.48-4.37, HR 2.40, CI 1.38-4.17, and HR 2.13, CI 1.02-4.46). Among patients discontinuing, 50.5% were due to questionable causes, such as sinus rhythm (33.9%), patients demand (10.1%) and falls (8.2%). The majority (43.1%) of treatment discontinuers were changed to aspirin, while 40.4% of them were left without medical stroke prophylaxis.

    Conclusions

    Although persistence to warfarin among AF patients proves higher than previously reported, there is room for improvement since half of the discontinuers have questionable reasons for treatment stop and the majority of them receive no other efficient stroke prophylaxis.

  • 2.
    Björck, Fredrik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Kadhim, Hayder
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Predictors for INR-control in a well-managed warfarin treatment setting2019Ingår i: Journal of Thrombosis and Thrombolysis, ISSN 0929-5305, E-ISSN 1573-742X, Vol. 47, nr 2, s. 227-232Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Warfarin is well studied in patients with non-valvular atrial fibrillation (AF). It has low complication rates for patients achieving individual Time in Therapeutic Range (iTTR)>70%. The risk scores SAMe-TT2R2 and PROSPER are designed to predict future TTR, but are derived from a heterogeneous population with generally low iTTR. The aim of this study was to evaluate predictors for high and low iTTR in an AF population in Sweden, where there is a generally good anticoagulation control. A retrospective register study based on Swedish warfarin dosing system AuriculA, including 28,011 AF patients starting treatment during 1 January 2006 to 31 December 2011. Complications and risk factors were analysed and related to iTTR. Mean age was 73.7 (SD +/- 9.5) years, with 42.0% women. Mean CHA(2)DS(2)-VASc score (SD) was 3.6 (+/- 1.7). For patients with iTTR<60% there were over three times higher prevalence of excessive alcohol consumption than for patients with iTTR>70% (3.7% vs. 1.1%). Previous stroke were more prevalent for patients with high than low iTTR (17.1% vs. 20.3%). Concomitant comorbidities were associated with increased risk of poor iTTR. In Swedish AF patients, excessive alcohol use is clearly associated with iTTR below 60%. Patients with previous stroke are more likely to get iTTR above 70%, unlike those with concomitant disorders who more often have poor anticoagulation control. The SAMe-TT2R2-score cannot be applied in Sweden.

  • 3.
    Björck, Fredrik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Renlund, Henrik
    Lip, Gregory Y. H.
    Wester, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Svensson, Peter J.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Outcomes in a Warfarin-Treated Population With Atrial Fibrillation2016Ingår i: JAMA cardiology, ISSN 2380-6583, E-ISSN 2380-6591, Vol. 1, nr 2, s. 172-180Artikel i tidskrift (Refereegranskat)
    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 CHA2DS2-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.

  • 4.
    Björck, Fredrik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Renlund, Henrik
    Svensson, Peter J
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Warfarin persistence among stroke patients with atrial fibrillation2015Ingår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 136, nr 4, s. 744-748Artikel i tidskrift (Refereegranskat)
    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 2years 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 CHA2DS2VASc 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 2years and 0.47 (95% CI 0.43 to 0.51) after 5years. 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 CHA2DS2VASc 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 CHA2DS2VASc score.

  • 5.
    Björck, Fredrik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sandén, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Renlund, Henrik
    Svensson, Peter J
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Warfarin treatment quality is consistently high in both anticoagulation clinics and primary care setting in Sweden2015Ingår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 136, nr 2, s. 216-220Artikel i tidskrift (Refereegranskat)
    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.

  • 6. Dahlen, Torsten
    et al.
    Edgren, Gustaf
    Höglund, Martin
    Lambe, Mats
    Björkholm, Magnus
    Sandin, Fredrik
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Richter, Johan
    Ohm, Lotta
    Back, Magnus
    Stenke, Leif
    Increased Risk of Cardiovascular Events Associated with TKI Treatment in Chronic Phase Chronic Myeloid Leukemia: Data from Swedish Population-Based Registries2014Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, nr 21Artikel i tidskrift (Övrigt vetenskapligt)
  • 7. Dahlen, Torsten
    et al.
    Edgren, Gustaf
    Lambe, Mats
    Hoglund, Martin
    Bjorkholm, Magnus
    Sandin, Fredrik
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Richter, Johan
    Olsson-Stromberg, Ulla
    Ohm, Lotta
    Back, Magnus
    Stenke, Leif
    Cardiovascular Events Associated With Use of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia: A Population-Based Cohort Study2016Ingår i: Annals of Internal Medicine, ISSN 0003-4819, E-ISSN 1539-3704, Vol. 165, nr 3, s. 161-166Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Tyrosine kinase inhibitors (TKIs) have increased survival dramatically for patients with chronic myeloid leukemia (CML), but continuous administration of these drugs may elicit long-term toxicity. Objective: To investigate the incidence of vascular events in patients with CML treated with first-and second-generation TKIs. Design: Retrospective cohort study using nationwide population-based registries. Setting: Sweden. Patients: All patients diagnosed with chronic-phase CML in Sweden from 2002 to 2012 and treated with a TKI, and 5 age- and sex-matched control individuals per patient. Measurements: Relative risks, expressed as incidence rate ratios comparing patients with control individuals, were calculated. Events per 1000 person-years were assessed in interdrug comparisons. Results: 896 patients, 94.4% with documented TKI treatment, were followed for a median of 4.2 years. There were 54 arterial and 20 venous events in the CML cohort, corresponding to relative risks of 1.5 (95% CI, 1.1 to 2.1) and 2.0 (CI, 1.2 to 3.3), respectively. The event rate for myocardial infarction was higher in patients treated with nilotinib or dasatinib (29 and 19 per 1000 person-years, respectively) than in those receiving imatinib (8 per 1000 person-years), although data are limited and the CIs were wide and overlapped. Among 31 patients treated with a TKI who had myocardial infarction, 26 (84%) had at least 1 major cardiac risk factor diagnosed before the event occurred. Limitations: Patients may have been exposed to multiple TKIs. Data on second-and third-generation TKIs were limited. Conclusion: An increased risk for arterial and venous vascular events was seen in patients with CML treated with a TKI. Further study is needed to determine whether the risk for myocardial infarction increases with second-generation drugs.

  • 8. Dimberg, Ivar
    et al.
    Grzymala-Lubanski, Bartosz
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Hägerfelth, Anette
    Rosenqvist, Mårten
    Svensson, Peter
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Computerised assistance for warfarin dosage: effects on treatment quality2012Ingår i: European journal of internal medicine, ISSN 0953-6205, E-ISSN 1879-0828, Vol. 23, nr 8, s. 742-744Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Well-managed warfarin treatment with a high time in therapeutic range (TTR) corresponds to fewer bleedings or thromboembolic complications. Many small centres manage their warfarin dosing manually, with little or no knowledge of their treatment quality as measured by TTR. AuriculA is a Swedish National web-based anticoagulation dosing system. Our hypothesis was that the web based dosing system, compared to manual dosing, would improve the TTR.

    Methods: Retrospective cohort study of medical records from patients with atrial fibrillation on warfarin treatment from two centres, with previously manual warfarin dosing regimens. Data for calculation of TTR was extracted manually from medical records from the time when using manual dosing and compared with the computerised regimen.

    Results: In centre 1, the mean TTR was significantly increased after the introduction of AuriculA, from 64.3% (95% CI 58.8-69.8) to 71.3% (95% CI 67.7-74.8), p=0.03. In centre 2, a high TTR of 73.6% (95% CI 71.3-75.9) was maintained after the implementation, 74.0% (95% CI 71.6-76.3). INR tests were prescribed significantly more frequent after the introduction of AuriculA in both centres; 20% more often at centre 1 and 21% at centre 2.

    Conclusion: Computerised dosing assistance within the Swedish national quality registry AuriculA improves or maintains a high treatment quality with warfarin as measured by TTR.

    (C) 2012 European Federation of Internal Medicine. Published by Elsevier B. V. All rights reserved.

  • 9.
    Grzymala-Lubanski, Bartosz
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Internal medicine, Sundsvall Hospital.
    Labaf, Ashkan
    Department for Coagulation Disorders, University of Lund, Malmö, Sweden.
    Englund, Erling
    Department of Research and Development, County Council of Västernorrland, Sundsvall Hospital, Sundsvall, Sweden.
    Svensson, Peter J.
    Department for Coagulation Disorders, University of Lund, Malmö, Sweden.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mechanical heart valve prosthesis and warfarin: treatment quality and prognosis2014Ingår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 133, nr 5, s. 795-798Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Every year about 2500 patients in Sweden undergo surgery due to heart valve disease. A mechanical heart valve prosthesis causes risk of thromboembolic stroke or thrombus formation in the valve while anticoagulant treatment increases the risk of bleeding. Treatment quality with warfarin is crucial for patients with mechanical valve prostheses. It has previously been shown that poorly controlled warfarin treatment increases mortality in this patient group. TTR (Time in Therapeutic Range) on warfarin has been shown to affect the risk of complications in atrial fibrillation, but has not been studied in patients with mechanical heart valves. Our aim is to evaluate the impact of TTR on the risk of complications in this patient group. Materials and Methods: A non-randomized, prospective study of 534 adults with mechanical heart valve prostheses from Malmo and Sundsvall registered in the Swedish National Quality Registry Auricula between 01.01.2008 and 31.12.2011. Quartiles regarding individual TTR levels were compared regarding risk of complications. Results: The risk of complications was significantly higher at lower TTR levels for all complications (p = 0.005), bleeding (p = 0.01) and death (p = 0.018) but not for thromboembolism. In multivariate analysis the risk was significantly increased at lower TTR levels for bleeding and all complications but not for death or thromboembolism. Conclusion: Patients with a lower warfarin treatment quality measured by TTR have a higher risk of complications such as severe bleeding or death. A TTR of 83% or higher at the individual level should be obtained for best outcome.

  • 10.
    Grzymala-Lubanski, Bartosz
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Själander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Renlund, Henrik
    Svensson, Peter J.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Computer aided warfarin dosing in the Swedish national quality registry AuriculA: algorithmic suggestions are performing better than manually changed doses2013Ingår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 131, nr 2, s. 130-134Artikel i tidskrift (Refereegranskat)
    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.

  • 11.
    Grzymala-Lubanski, Bartosz
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Svensson, Peter J.
    Renlund, Henrik
    Jeppsson, Anders
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Warfarin treatment quality and prognosis in patients with mechanical heart valve prosthesis2017Ingår i: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 103, nr 3, s. 198-203Artikel i tidskrift (Refereegranskat)
    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).

  • 12.
    Gunnarsson, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Höglund, M.
    Stenke, L.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Sandin, F.
    Björkholm, M.
    Dreimane, A.
    Lambe, M.
    Markevärn, Berit
    Olsson-Strömberg, U.
    Wadenvik, H.
    Richter, J.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Increased prevalence of prior malignancies and autoimmune diseases in patients diagnosed with chronic myeloid leukemia2016Ingår i: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 30, nr 7, s. 1562-1567Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We recently reported an increased incidence of second malignancies in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKI). To elucidate whether this increase may be linked, not to TKI but rather to a hereditary or acquired susceptibility to develop cancer, we estimated the prevalence of malignancies, autoimmune disease (AD) and chronic inflammatory disease (CID) in CML patients prior to their CML diagnosis. Nationwide population-based registers were used to identify patients diagnosed with CML in Sweden 2002-2012 and to estimate the prevalence of other malignancies, AD and CID prior to their CML diagnosis. For each patient with CML, five matched controls were selected from the general population. Conditional logistic regression was used to calculate odds ratios (OR). Nine hundred and eighty-four CML patients were assessed, representing more than 45 000 person-years of follow-up. Compared with matched controls, the prevalence of prior malignancies and AD was elevated in CML patients: OR 1.47 (95% confidence interval (CI) 1.20-1.82) and 1.55 (95% CI 1.21-1.98), respectively. No associations were detected between CML and previous CID. An increased prevalence of other malignancies and AD prior to the diagnosis of CML suggest that a hereditary or acquired predisposition to cancer and/or autoimmunity is involved in the pathogenesis of CML.

  • 13.
    Gunnarsson, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Höglund, Martin
    Stenke, Leif
    Wållberg Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Sandin, Fredrik
    Björkholm, Magnus
    Dreimane, Arta
    Lambe, Mats
    Markevärn, Berit
    Olsson-Strömberg, Ulla
    Wadenvik, Hans
    Richter, Johan
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Increased Prevalence of Prior Malignancies and Autoimmune Diseases in Patients Diagnosed with Chronic Myeloid Leukemia2015Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, nr 23Artikel i tidskrift (Övrigt vetenskapligt)
  • 14.
    Gunnarsson, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Leif, Stenke
    Hoglund, Martin
    Sandin, Fredrik
    Bjorkholm, Magnus
    Dreimane, Arta
    Lambe, Mats
    Markevärn, Berit
    Olsson-Stromberg, Ulla
    Richter, Johan
    Wadenvik, Hans
    Wallvik, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Second Malignancies Following Treatment of Chronic Myeloid Leukemia in the Tyrosine Kinase Inhibitor Era2014Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, nr 21Artikel i tidskrift (Övrigt vetenskapligt)
  • 15.
    Gunnarsson, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sandin, Fredrik
    Höglund, Martin
    Stenke, Leif
    Björkholm, Magnus
    Lambe, Mats
    Olsson-Strömberg, Ulla
    Richter, Johan
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Population-based assessment of chronic myeloid leukemia in Sweden: striking increase in survival and prevalence2016Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 97, nr 4, s. 387-392Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The clinical outcome for patients with chronic myeloid leukemia (CML) has improved dramatically following the introduction of tyrosine kinase inhibitors. An improved survival, combined with a constant incidence, is expected to increase the prevalence of CML. However, data on the prevalence of CML remain scarce. We examined the overall and relative (age and gender matched) survival and assessed the past, present, and projected future prevalence of CML in Sweden. Data on all patients diagnosed with CML between 1970 and 2012 were retrieved from the Swedish Cancer Register and the Swedish Cause of Death Register. The 5-year overall survival increased from 0.18 to 0.82, during the observed time period. Between 2006 and 2012, the 5-year relative survival was close to normal for 40-year-old, but considerably lower for 80-year-old CML patients. The observed prevalence tripled from 1985 to 2012, from 3.9 to 11.9 per 100 000 inhabitants. Assuming no further improvements in relative survival, the prevalence is projected to further increase by 2060 to 22.0 per 100 000 inhabitants (2587 persons in Sweden). The projected dramatic increase in CML prevalence has major medical and health economic implications and needs to be considered in planning how to organize future care of CML patients.

  • 16.
    Gunnarsson, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Stenke, Leif
    Höglund, Martin
    Sandin, Fredrik
    Björkholm, Magnus
    Dreimane, Arta
    Lambe, Mats
    Markevärn, Berit
    Department of Haematology, University Hospital, Umeå.
    Olsson-Strömberg, Ulla
    Richter, Johan
    Wadenvik, Hans
    Wallvik, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Second malignancies following treatment of chronic myeloid leukaemia in the tyrosine kinase inhibitor era2015Ingår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 169, nr 5, s. 683-688Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Given that tyrosine kinase inhibitors (TKIs) have dramatically improved the survival of patients with chronic myeloid leukaemia (CML), we were interested in examining the possible risk of long-term adverse events, such as the emergence of other neoplasms. Therefore, we studied the development of second malignancies in 868 patients diagnosed with CML between 2002 and 2011 using the Swedish CML register, cross-linked to the Swedish Cancer register. With a median follow-up of 3·7 (range 0-9·9) years, 65 (7·5%) patients developed 75 second malignancies (non-haematological), 52 of which were of the invasive type. Compared to expected rates in the background population, the risk of second malignancies was higher in the CML cohort, with a standardized incidence ratio (SIR) of 1·52 (95% CI 1·13-1·99). The SIR before and after the second year following diagnosis of CML was 1·58 and 1·47, respectively. Among specific cancer types, gastrointestinal and nose and throat cancer were significantly increased. Founded on a population-based material, our results indicate that CML patients treated in the TKI era are at an increased risk of developing a second malignancy, with indications that this risk may more likely be linked to CML itself rather than to the TKI treatment.

  • 17.
    Hultin, Magnus
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Edin, Benoni B.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Two Years Experiences of a new Swedish National Proficiency Test for Doctors of Medicine.2018Ingår i: Abstract book, undee, 2018Konferensbidrag (Refereegranskat)
  • 18.
    Hultin, Magnus
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Edin, Benoni
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Warglo, Zara
    Socialstyrelsen.
    Wennberg, Åsa
    Socialstyrelsen.
    Sänkta krav på utländska läkare vore förödande2018Ingår i: Dagens Samhälle, ISSN 1652-6511, nr 4 decArtikel i tidskrift (Övrig (populärvetenskap, debatt, mm))
    Abstract [sv]

    Det är avgörande att det ställs samma höga krav på läkare från länder utanför EU som på svenskutbildade. Bilden av att det ställs olika krav på olika grupper vore förödande, skriver ansvariga för kunskapsprovet för läkare vid Umeå universitet ihop med Socialstyrelsen.

  • 19. Höglund, Martin
    et al.
    Sandin, Fredrik
    Hellström, Karin
    Björeman, Mats
    Björkholm, Magnus
    Brune, Mats
    Dreimane, Arta
    Ekblom, Marja
    Lehmann, Sören
    Ljungman, Per
    Malm, Claes
    Markevärn, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Myhr-Eriksson, Kristina
    Ohm, Lotta
    Olsson-Strömberg, Ulla
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Wadenvik, Hans
    Simonsson, Bengt
    Stenke, Leif
    Richter, Johan
    Tyrosine kinase inhibitor usage, treatment outcome, and prognostic scores in CML: report from the population-based Swedish CML registry2013Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 122, nr 7, s. 1284-1292Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Clinical management guidelines on malignant disorders are generally based on data from clinical trials with selected patient cohorts. In Sweden, more than 95% of all patients diagnosed with chronic myeloid leukemia (CML) are reported to the national CML registry, providing unique possibilities to compile population-based information. This report is based on registry data from 2002 to 2010, when a total of 779 patients (425 men, 354 women; median age, 60 years) were diagnosed with CML (93% chronic, 5% accelerated, and 2% blastic phase) corresponding to an annual incidence of 0.9/100 000. In 2002, approximately half of the patients received a tyrosine kinase inhibitor as initial therapy, a proportion that increased to 94% for younger (<70 years) and 79% for older (>80 years) patients during 2007-2009. With a median follow-up of 61 months, the relative survival at 5 years was close to 1.0 for patients younger than 60 years and 0.9 for those aged 60 to 80 years, but only 0.6 for those older than 80 years. At 12 months, 3% had progressed to accelerated or blastic phase. Sokal, but not European Treatment and Outcome Study, high-risk scores were significantly linked to inferior overall and relative survival. Patients living in university vs nonuniversity catchment areas more often received tyrosine kinase inhibitors up front but showed comparable survival.

  • 20. Ilander, M
    et al.
    Olsson-Strömberg, U
    Schlums, H
    Guilhot, J
    Brück, O
    Lähteenmäki, H
    Kasanen, T
    Koskenvesa, P
    Söderlund, S
    Höglund, M
    Markevärn, B
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lotfi, K
    Dreimane, A
    Lübking, A
    Holm, E
    Björeman, M
    Lehmann, S
    Stenke, L
    Ohm, L
    Gedde-Dahl, T
    Majeed, W
    Ehrencrona, H
    Koskela, S
    Saussele, S
    Mahon, F-X
    Porkka, K
    Hjorth-Hansen, H
    Bryceson, Y T
    Richter, J
    Mustjoki, S
    Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia2017Ingår i: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 31, nr 5, s. 1108-1116Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recent studies suggest that a proportion of chronic myeloid leukemia (CML) patients in deep molecular remission can discontinue the tyrosine kinase inhibitor (TKI) treatment without disease relapse. In this multi-center, prospective clinical trial (EURO-SKI, NCT01596114) we analyzed the function and phenotype of T and NK cells and their relation to successful TKI cessation. Lymphocyte subclasses were measured from 100 imatinib treated patients at baseline and 1 month after the discontinuation, and functional characterization of NK and T cells was done from 45 patients. The proportion of NK cells was associated with the molecular relapse free survival as patients with higher than median NK-cell percentage at the time of drug discontinuation had better probability to stay in remission. Similar association was not found with T or B cells or their subsets. In non-relapsing patients the NK-cell phenotype was mature, whereas patients with more naïve CD56(bright) NK cells had decreased relapse free survival. In addition, the TNF-α/IFN-γ cytokine secretion by NK cells correlated with the successful drug discontinuation. Our results highlight the role of NK cells in sustaining remission and strengthen the status of CML as an immunogenic tumor warranting novel clinical trials with immunomodulating agents.

  • 21. Ilander, Mette Matilda
    et al.
    Olsson-Strömberg, Ulla
    Lahteenmaki, Hanna
    Tiina, Kasanen
    Koskenvesa, Perttu
    Söderlund, Stina
    Höglund, Martin
    Markevärn, Berit
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lotfi, Kourosh
    Malm, Claes
    Lubking, Anna
    Ekblom, Marja
    Holm, Elena
    Bjoreman, Mats
    Lehmann, Soren
    Stenke, Leif
    Ohm, Lotta
    Majeed, Waleed
    Pfirrmann, Markus
    Muller, Martin C.
    Guilhot, Joelle
    Ehrencrona, Hans
    Hjorth-Hansen, Henrik
    Saussele, Susanne
    Mahon, Francois-Xavier
    Porkka, Kimmo
    Richter, Johan
    Mustjoki, Satu
    Early Disease Relapse after Tyrosine Kinase Inhibitor Treatment Discontinuation in CML Is Related Both to Low Number and Impaired Function of NK-Cells2014Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, nr 21Artikel i tidskrift (Övrigt vetenskapligt)
  • 22. Ilander, Mette
    et al.
    Olsson-Stromberg, Ulla
    Lahteenmaki, Hanna
    Kasanen, Tiina
    Koskenvesa, Perttu
    Soderlund, Stina
    Hoglund, Martin
    Markevärn, Berit
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lofti, Kouros
    Malm, Claes
    Lubking, Anna
    Ekblom, Marja
    Holm, Elena
    Bjoreman, Mats
    Lehmann, Soren
    Stenke, Leif
    Ohm, Lotta
    Hjorth-Hansen, Henrik
    Saussele, Susanne
    Mahon, Francois-Xavier
    Porkka, Kimmo
    Richter, Johan
    Mustjoki, Satu
    Disease Relapse After Tyrosine Kinase Inhibitor Treatment Discontinuation in Chronic Myeloid Leukaemia is Related to Both Low Number and Impaired Function of NK Cells2014Ingår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 79, nr 6, s. 467-468Artikel i tidskrift (Övrigt vetenskapligt)
  • 23. Ilander, Mette
    et al.
    Schlums, Heinrich
    Olsson-Stromberg, Ulla
    Lahteenmäki, Hanna
    Kasanen, Tiina
    Koskenvesa, Perttu
    Söderlund, Stina
    Höglund, Martin
    Markevärn, Berit
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Lotfi, Kourosh
    Malm, Claes
    Lubking, Anna
    Ekblom, Marja
    Holm, Elena
    Björeman, Mats
    Lehmann, Soren
    Stenke, Leif
    Ohm, Lotta
    Majeed, Waleed
    Muller, Martin C
    Ehrencrona, Hans
    Hjorth-Hansen, Henrik
    Saussele, Susanne
    Mahon, Francois-Xavier
    Porkka, Kimmo
    Guilhot, Joelle
    Bryceson, Yenan
    Richter, Johan
    Mustjoki, Satu
    Mature, Adaptive-like CD56(DIM) NK Cells in Chronic Myeloid Leukemia Patients in Treatment Free Remission2015Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, nr 23Artikel i tidskrift (Övrigt vetenskapligt)
  • 24. Labaf, A.
    et al.
    Stagmo, M.
    Wieloch, M.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Svensson, P. J.
    Predictive accuracies of CHA2DS2-VASc and HAS-BLED, and anticoagulation quality in relation to thromboemblism and bleeding in patients with mechanical heart valves2013Ingår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, nr Supplement: 1, s. 379-379Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: The variability of international normalized ratio (INR) is considered a risk factor in patients with mechanical heart valves (MHV)and INR target range still remains unestablished. CHA2DS2-VASc andHAS-BLED are risk stratification schemas designed for atrial fibrillation. Their ability to discriminate thromboembolism (TE) and bleeding for patients with MHV have never been investigated.

    Methods: We conducted a complete study of all patients with MHV followed in two centres. A total of 407 and 140 patients respectively were followed between 2008-2011. Data on INR, time in therapeutic range (TTR), variability, CHA2DS2-VASc and HAS-BLED were extracted.

    Results: The mean (±SD) age in centre 1 and 2 were 70 (14) and 61 (14) respectively. The target INR range for all MHV was 2-4 in centre 1 and 2-3 in centre 2 and mean INR was 2.9 (0.31) and 2.6 (0.19) respectively. The incidence of TE was 3.4 per 100 patient-years in centre 1 and 1.4 per 100 patient-years in centre 2, p=0.035, and for major bleeding 4.9 per 100 patient-years and 1.7 per 100 patient-years respectively, p=0.005. TheHAS-BLED score correlated well with bleeding, with area under the curveof 0.63 (95% confidence interval [CI]: 0.57-0.70). CHA2DS2-VASc had 0.56 (95% CI: 0.48-0.64) for TE. Adding atrial fibrillation as a risk factor did not improve the c statistic. INR variability (SD), comparing the 3rd tertile with the first had (Odds ratio [OR]: 4.05; 95% [CI]: 2.09-7.84) for major bleeding and (OR: 2.01; 95% [CI]: 1.0-3.99) for TE. INR SD was higher with a higher mean INR and target range 2-4 (p<0.001) andindependently predicted bleeding.

    Conclusion: HAS-BLED predicted bleeding with discriminatory ability similar to previous reports to atrial fibrillation whilst CHA2DS2-VAScpredictive ability for TE was modest. Higher INR intensity is associated with higher variability, which correlates to primarily bleeding, but also TE. Some of the difference between the groups considering TE can be accounted for more significant risk factors in the centre 1 cohort. A more narrow INR target range could be recommended to reduce variability ofanticoagulation.

  • 25. Labaf, Ashkan
    et al.
    Grzymala-Lubanski, Bartosz
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Svensson, Peter J
    Stagmo, Martin
    Glomerular filtration rate and association to stroke, major bleeding, and death in patients with mechanical heart valve prosthesis2015Ingår i: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 170, nr 3, s. 559-565Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS: The impact of estimated glomerular filtration rate (eGFR) on adverse events in patients with mechanical heart valves (MHVs) is unknown. We analyzed the independent association of eGFR and thromboembolism (TE), major bleeding, and mortality in patients with MHV in an observational cohort study.

    METHODS AND RESULTS: All patients (n = 520) with MHV replacement on anticoagulation treatment were followed up prospectively regarding TE, major bleeding, and death at 2 anticoagulation centers during 2008 to 2011. The mean age was 69 years, 72% with aortic valve replacement, and time in therapeutic range 2.0 to 4.0 was 91%. The incidence of the combined end point of major bleeding, TE, and death increased sharply with each decreasing eGFR stratum: 5.5, 8.4, 16, and 32 per 100 patient-years for eGFR >60, 45 to 60, 30 to 45, and <30 mL/min per 1.73 m(2), respectively. After multivariate adjustment for comorbidities, every unit decrease in eGFR increased the risk of major bleeding by 2%, death by 3%, and the combined end point by 1%. There was no association between eGFR and TE. There was an increased proportion of international normalized ratio >3.0 and >4.0 and decreasing time in therapeutic range for each decreasing eGFR stratum (P < .001 for trend). The hazard ratios of the combined end point for eGFR <30, 30 to 45, and 45 to 60 mL/min per 1.73 m(2) were 3.2 (95% CI 1.8-5.6), 1.5 (95% CI 0.9-2.5), and 0.9 (95% CI 0.6-1.5), respectively, compared to eGFR >60 mL/min per 1.73 m(2).

    CONCLUSION: In patients with MHV on anticoagulation, eGFR is an independent predictor of major bleeding and death and not TE.

  • 26. Labaf, Ashkan
    et al.
    Grzymala-Lubanski, Bartosz
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Internal Medicine, General Hospital in Sundsvall, Sundsvall, Sweden.
    Stagmo, Martin
    Lövdahl, Susanna
    Wieloch, Mattias
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Internal Medicine, General Hospital in Sundsvall, Sundsvall, Sweden.
    Svensson, Peter J.
    Thromboembolism, major bleeding and mortality in patients with mechanical heart valves: a population-based cohort study2014Ingår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 134, nr 2, s. 354-359Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Low incidences of thromboembolism (TE) and bleeding in patients with mechanical heart valves (MHV) have previously been reported. This study assesses the incidence of and clinical risk factors predicting TE, major bleeding and mortality in a clinical setting. Methods and results: All 546 patients undergoing anticoagulation treatment due to MHV replacement at hospitals in Malmo and Sundsvall in Sweden were monitored during 2008-2011 and the incidence of TE, major bleeding and mortality was prospectively followed. There were 398, 122 and 26 patients in the aortic group (AVR), mitral (MVR) group and the combined aortic/mitral valve group respectively. The incidence of TE was 1.8 and 2.2 per 100 patient-years in the AVR group MVR group respectively. The corresponding incidences of bleeding were 4.4 and 4.6, respectively. Independent predictor of thromboembolism was vascular disease (Odds ratio {OR}: 4.2; 95% CI: 1.0-17.4). Predictor of bleeding was previous bleeding (OR: 2.7; 95% CI: 1.4-5.3). Independent predictors of mortality was age (Hazard ratio {HR}: 1.03; 95% CI: 1.00-1.05), hypertension (HR: 2.4; 95% CI: 1.3-4.5), diabetes (HR: 2.4; 95% CI: 1.3-4.3) and alcohol overconsumption (HR: 5.2; 95% CI: 1.7-15.9). Standardized mortality/morbidity ratio for mortality and AMI was 0.99 (95% CI: 0.8-1.2) and 0.87 (95% CI: 0.5-1.2) respectively. Conclusion: The incidence of TE and major bleeding in this unselected clinical population exceeds that of previously reported retrospective and randomized trials. Despite this, mortality is equal to that of the general population.

  • 27. Labaf, Ashkan
    et al.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Stagmo, Martin
    Svensson, Peter J
    INR variability and outcomes in patients with mechanical heart valve prosthesis2015Ingår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 136, nr 6, s. 1211-1215Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The quality of treatment with warfarin is mainly assessed by the time in therapeutic range (TTR) in patients with mechanical heart valve prosthesis (MHV). Our aim was to evaluate if International Normalized Ratio (INR) variability predicted a combined endpoint of thromboembolism, major bleeding and death better than TTR.

    METHODS AND RESULTS: We included 394 patients at one center with MHV during 2008-2011 with adverse events and death followed prospectively. TTR 2.0-4.0 and log-transformed INR variability was calculated for all patients. In order to make comparisons between the measures, the gradient of the risk per one standard deviation (SD) was assessed. INR variability performed equal as TTR 2.0-4.0 per one SD unit adjusted for covariates, hazard ratio (HR) 1.30 (95% CI 1.1-1.5) and 0.71 (95% CI 0.6-0.8) respectively for the combined endpoint, and performed better for mortality HR 1.47 (95% CI 1.1-1.9) and 0.70 (95% CI 0.6-0.8). INR variability was categorized into high and low group and TTR into tertiles. High variability within the low and high TTR, had a HR 2.0 (95% CI 1.7-3.6) and 2.2 (95% CI 1.1-4.1) respectively, of the combined endpoint compared to the low variability/high TTR group. INR values <2.0 greatly increased the rate of thromboembolism whereas the rate of major bleeding increased moderately between INR 3.0 and 4.0 and increased substantially after INR >4.0.

    CONCLUSION: The INR variability is an equal predictor as TTR of the combined endpoint of thromboembolism, major bleeding and death, and adds important information on top of TTR in patients with MHV.

  • 28. Labaf, Ashkan
    et al.
    Svensson, Peter J
    Renlund, Henrik
    Jeppsson, Anders
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Incidence and risk factors for thromboembolism and major bleeding in patients with mechanical valve prosthesis: a nationwide population-based study2016Ingår i: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 181, s. 1-9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Risk factors of stroke/thromboembolism (TE) and major bleeding, and incidence of these events in specific age categories in warfarin-treated patients with mechanical heart valves (MHV) are uncertain. Our objective was to calculate event rates in specific age categories and identify risk factors for adverse events.

    METHODS AND RESULTS: We identified 4,810 treatment periods with MHV between January 2006 and December 2011 in the Auricula and Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registries. There were 3,751 treatment periods with aortic valve replacements (AVR) and 866 with mitral valve replacements (MVR). Median follow-up time was 4.5 years (IQR, 1.5-6.0). Time in therapeutic range with warfarin for patients with AVR was 74.2% for international normalized ratio of 2.0 to 3.0, with 72% of the patients having this target range. Rate of stroke/TE for AVR and MVR was 1.3 and 1.6 per 100 patient years, respectively (P=.20). The rate of first major bleeding was 2.6 and 3.9 per 100 patient years with AVR and MVR, respectively (P<.001). By multivariate analysis for AVR, age (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.01-1.03 per year) and previous stroke (HR, 2.4; 95% CI, 1.7-3.5) emerged as independent risk factors for stroke/TE. Heart failure (HR, 0.9; 95% CI, 0.6-1.4) and atrial fibrillation (HR, 1.0; 95% CI, 0.7-1.4) were not associated to stroke/TE. For major bleeding events, age (HR, 1.02; 95% CI, 1.01-1.03 per year) and previous major bleeding (HR, 2.5; 95% CI, 1.9-3.3) emerged as independent risk factors for AVR.

    CONCLUSIONS: In a nationwide cohort study with MHV and high time in therapeutic range, heart failure and atrial fibrillation did not appear as risk factors of stroke/TE.

  • 29. Larfors, Gunnar
    et al.
    Sandin, Fredrik
    Richter, Johan
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Stenke, Leif
    Lambe, Mats
    Höglund, Martin
    The impact of socio-economic factors on treatment choice and mortality in chronic myeloid leukaemia2017Ingår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 98, nr 4, s. 398-406Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: To evaluate the influence of socio-economic variables on treatment selection and survival of patients with chronic myeloid leukaemia (CML).

    METHODS: Using information available in population-based Swedish registries, we evaluated indices of health, education and economy from the 980 patients in the Swedish CML register diagnosed between 2002 and 2012. Apart from internal comparisons, five age-, gender- and region-matched control subjects per patient served as control cohort. Median follow-up time from CML diagnosis was 4.8 years.

    RESULTS: Among patients with CML, low personal or household income, short education, living alone, poor performance status and high age (>60 years) were significantly associated with an inferior survival (in univariate analyses). However, similar findings were noted also in the matched control group, and in comparisons adjusted for calendar year, age and performance status, socio-economic variables were not significantly associated with CML survival. Meanwhile, both education and income were independently linked to TKI treatment overall and to upfront treatment with second-generation TKIs.

    CONCLUSIONS: In conclusion, socio-economic conditions were associated with survival in the studied CML cohort but these associations could be explained by differences at baseline. Meanwhile, socio-economic conditions appeared to influence treatment choice.

  • 30. Mochalina, Natalia
    et al.
    Isma, Nazim
    Svensson, Peter J.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Carlsson, Maj
    Juhlin, Tord
    Wieloch, Mattias
    Ischemic stroke rates decline in patients with atrial fibrillation as anticoagulants uptake improves: A Swedish cohort study2017Ingår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 158, s. 44-48Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: The impact of the increased anticoagulants uptake on incidence rate of ischemic stroke is largely unknown. We assessed time trends in rates of ischemic stroke in patients with incident atrial fibrillation (AF) diagnosed between 2011 and 2013.

    Materials and methods: Population-based retrospective registry study of all 11,500 adults diagnosed with incident non-valvular atrial fibrillation in 2011-2013 in primary and secondary care and receiving oral anticoagulants (n = 4847), aspirin (n = 2850) or no treatment (n = 3766) in Skane County, Sweden. The primary outcome was the rate of ischemic stroke within 365 days after AF diagnosis.

    Results and conclusion: Cumulative incidence of ischemic stroke decreased from 2.87% (95% confidence interval (CI) 2.37-3.45%) to 1.93% (95% CI 1.54-2.41%) while the uptake of oral anticoagulants increased from 36.6% to 48.4% between 2011 and 2013 (regression coefficient - 0.08; 95% CI, - 0.09 to - 0.07, p < 0.001). The increased uptake of oral anticoagulants in the community is associated with decreased incidence of ischemic stroke in AF patients.

  • 31. Mochalina, Natalia
    et al.
    Jöud, Anna
    Carlsson, Maj
    Sandberg, Maria E. C.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Juhlin, Tord
    Svensson, Peter J.
    Antithrombotic therapy in patientswith non-valvular atrial fibrillation in Southern Sweden: A population-based cohort study2016Ingår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 140, s. 94-99Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Oral anticoagulants in patients with atrial fibrillation (AF) with moderate-to-high stroke risk are strongly recommended by the current guidelines.

    Materials and methods: Population-based register study of all 13,837 patients with incident non-valvular AF diagnosed during 2011-2014 in primary and secondary care (including all in-and outpatient visits) in Skane County, Sweden. The outcome was the prescription of direct-acting oral anticoagulants (DOAC), warfarin or acetylsalicylic acid (ASA).

    Results and conclusion: Guideline adherence increased from 47.6% in 2011 to 66.1% in 2014, mostly due to decrease in undertreatment. In patients with CHA(2)DS(2)-VASc score >= 2, ASA uptake decreased from 29.9% to 14.7% and DOAC uptake increased from 2.1% to 25.1%. The use of ASA was more common among elderly and with increasing stroke-and bleeding risk. Overall, 47.4% of patients with CHA(2)DS(2)-VASc score >= 2 did not receive oral anticoagulants. Undertreatment was particularly common in women < 65 years (55.8%) and in patients >84 years (65.3% in women and 62% in men). Overtreatment of patients at low stroke risk was 35.9% in men and 36.4% in women. Provider speciality affected the choice of treatment only to a minor degree. Despite increasing guideline adherence, there is a suboptimal use of antithrombotic therapy in a large proportion of AF patients diagnosed in different clinical settings. Efforts to further improve guideline adherence should particularly be targeted on women < 65 years, elderly > 84 years and patients at low stroke risk.

  • 32. Richter, Johan
    et al.
    Söderlund, Stina
    Lübking, Anna
    Dreimane, Arta
    Lotfi, Kourosh
    Markevärn, Berit
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Saussele, Susanne
    Olsson-Strömberg, Ulla
    Stenke, Leif
    Musculoskeletal pain in patients with chronic myeloid leukemia after discontinuation of Imatinib: a Tyrosine Kinase Inhibitor withdrawal syndrome?2014Ingår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 32, nr 25, s. 2821-2823Artikel i tidskrift (Refereegranskat)
  • 33.
    Sandén, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Renlund, Henrik
    Svensson, Peter J.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Bleeding complications and mortality in warfarin-treated VTE patients, dependence of INR variability and iTTR2017Ingår i: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 117, nr 1, s. 27-32Artikel i tidskrift (Refereegranskat)
    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.

  • 34.
    Sandén, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Renlund, Henrik
    Svensson, Peter J.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Bleeding complications in venous thrombosis patients on well-managed warfarin2016Ingår i: Journal of Thrombosis and Thrombolysis, ISSN 0929-5305, E-ISSN 1573-742X, Vol. 41, nr 2, s. 351-358Artikel i tidskrift (Refereegranskat)
    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.

  • 35.
    Sandén, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Renlund, Henrik
    Svensson, Peter J
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Warfarin treatment complications do not correlate to cTTR when above 70%2015Ingår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 136, nr 6, s. 1185-1189Artikel i tidskrift (Refereegranskat)
    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 179,624treatmentyears, 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.

  • 36.
    Sandén, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
    Svensson, Peter J
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Venous thromboembolism and cancer risk2017Ingår i: Journal of Thrombosis and Thrombolysis, ISSN 0929-5305, E-ISSN 1573-742X, Vol. 43, nr 1, s. 68-73Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cancer increases the risk of venous thromboembolism (VTE) and about 20 % of all VTE are associated with cancer. VTE can also be used as a marker for occult cancer. The objective was to examine the correlation between VTE and cancer regarding predictors for a subsequent cancer diagnosis. Patients treated for VTE between January 1st 2006 and December 31th 2011 were extracted from the Swedish national quality register AuriculA and crossmatched with the Swedish National Patient Register. In total 7854 patients corresponding to 14284 treatments years were examined. Primary VTE was found in 6451 patients, with 3936 first and 2515 recurrent VTE. There were 1403 patients with secondary VTE. After a first or recurrent primary VTE the incidence of cancer diagnose was high being 9.4-10.0 % the first year compared to 2.7-2.5 % during the second year. Cancer in the digestive organs was the most common type of cancer among those with first primary VTE with 19.2 % of diagnoses. In multivariable analysis age was found to increase the risk of cancer diagnosis after both first and recurrent primary VTE HR 1.02 (CI 1.02-1.03) and HR 1.02 (CI 1.01-1.03). For a first primary VTE anemia HR 2.13 (CI 1.48-3.08) and male sex HR 1.38 (CI 1.09-1.76) increased the risk while hypertension HR 0.74 (0.57-0.96), dementia HR 0.30 (CI 0.10-0.95) and history of major bleeding HR 0.52 (CI 0.28-0.97) reduced the risk of a subsequent cancer diagnosis. There is a substantial proportion of patients being diagnosed with cancer the first year after a primary VTE, anaemia and male sex confers an increased risk.

  • 37. Simonsson, Bengt
    et al.
    Gedde-Dahl, Tobias
    Markevärn, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Remes, Kari
    Stentoft, Jesper
    Almqvist, Anders
    Björeman, Mats
    Flogegard, Max
    Koskenvesa, Perttu
    Lindblom, Anders
    Malm, Claes
    Mustjoki, Satu
    Myhr-Eriksson, Kristina
    Ohm, Lotta
    Räsänen, Anu
    Sinisalo, Marjatta
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Strömberg, Ulla
    Bjerrum, Ole Weiss
    Ehrencrona, Hans
    Gruber, Franz
    Kairisto, Veli
    Olsson, Karin
    Sandin, Fredrik
    Nagler, Arnon
    Nielsen, Johan Lanng
    Hjorth-Hansen, Henrik
    Porkka, Kimmo
    Combination of pegylated IFN-alpha 2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia2011Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 118, nr 12, s. 3228-3235Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Biologic and clinical observations suggest that combining imatinib with IFN-alpha may improve treatment outcome in chronic myeloid leukemia (CML). We randomized newly diagnosed chronic-phase CML patients with a low or intermediate Sokal risk score and in imatinib-induced complete hematologic remission either to receive a combination of pegylated IFN-alpha 2b (Peg-IFN-alpha 2b) 50 mu g weekly and imatinib 400 mg daily (n = 56) or to receive imatinib 400 mg daily monotherapy (n = 56). The primary endpoint was the major molecular response (MMR) rate at 12 months after randomization. In both arms, 4 patients (7%) discontinued imatinib treatment (1 because of blastic transformation in imatinib arm). In addition, in the combination arm, 34 patients (61%) discontinued Peg-IFN-alpha 2b, most because of toxicity. The MMR rate at 12 months was significantly higher in the imatinib plus Peg-IFN-alpha 2b arm (82%) compared with the imatinib monotherapy arm (54%; intention-to-treat, P = .002). The MMR rate increased with the duration of Peg-IFN-alpha 2b treatment (< 12-week MMR rate 67%, > 12-week MMR rate 91%). Thus, the addition of even relatively short periods of Peg-IFN-alpha 2b to imatinib markedly increased the MMR rate at 12 months of therapy. Lower doses of Peg-IFN-alpha 2b may enhance tolerability while retaining efficacy and could be considered in future protocols with curative intent.

  • 38.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Low-molecular-weight heparin prophylaxis does not affect mortality in acutely ill medical patients at low risk for venous thromboembolism2012Ingår i: Evidence-Based Medicine, ISSN 1356-5524, E-ISSN 1473-6810, Vol. 17, nr 6, artikel-id e12Artikel i tidskrift (Refereegranskat)
  • 39.
    Själander, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Jeppsson, Anders
    Svensson, Peter J
    [Guidelines for anticoagulation in patients with valve prosthesis. More supposition than scientific evidence].2010Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, nr 39, s. 2326-2328Artikel i tidskrift (Refereegranskat)
  • 40.
    Själander, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Missios, Anna
    Mulugeta, Elsa
    Wetterlöv, Therese
    Svensson, Peter J
    [Investigation of thrombosis: only when the patient benefits from the results]2010Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, nr 10, s. 679-681Artikel i tidskrift (Refereegranskat)
  • 41.
    Själander, Sara
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Holmqvist, Fredrik
    Smith, J Gustav
    Platonov, Pyotr G
    Kesek, Milos
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Svensson, Peter J
    Blomström-Lundqvist, Carina
    Tabrizi, Fariborz
    Tapanainen, Jari
    Poci, Dritan
    Jönsson, Anders
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Assessment of use vs discontinuation of oral anticoagulation after pulmonary vein isolation in patients with atrial fibrillation2017Ingår i: JAMA cardiology, ISSN 2380-6583, E-ISSN 2380-6591, Vol. 2, nr 2, s. 146-152Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Importance: Pulmonary vein isolation (PVI) is a recommended treatment for patients with atrial fibrillation, but it is unclear whether it results in a lower risk of stroke.

    Objectives: To investigate the proportion of patients discontinuing anticoagulation treatment after PVI in association with the CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years [doubled], diabetes, stroke [doubled], vascular disease, age 65-74 years, sex category [female]) score, identify factors predicting stroke after PVI, and explore the risk of cardiovascular events after PVI in patients with and without guideline-recommended anticoagulation treatment.

    Design, Setting, and Participants: A retrospective cohort study was conducted using Swedish national health registries from January 1, 2006, to December 31, 2012, with a mean-follow up of 2.6 years. A total of 1585 patients with atrial fibrillation undergoing PVI from the Swedish Catheter Ablation Register were included, with information about exposure to warfarin in the national quality register Auricula. Data analysis was performed from January 1, 2015, to April 30, 2016.

    Exposures: Warfarin treatment.

    Main Outcomes and Measures: Ischemic stroke, intracranial hemorrhage, and death.

    Results: In this cohort of 1585 patients, 73.0% were male, the mean (SD) age was 59.0 (9.4) years, and the mean (SD) CHA2DS2-VASc score was 1.5 (1.4). Of the 1585 patients, 1175 were followed up for more than 1 year after PVI. Of these, 360 (30.6%) discontinued warfarin treatment during the first year. In patients with a CHA2DS2-VASc score of 2 or more, patients discontinuing warfarin treatment had a higher rate of ischemic stroke (5 events in 312 years at risk [1.6% per year]) compared with those continuing warfarin treatment (4 events in 1192 years at risk [0.3% per year]) (P = .046). Patients with a CHA2DS2-VASc score of 2 or more or those who had previously experienced an ischemic stroke displayed a higher risk of stroke if warfarin treatment was discontinued (hazard ratio, 4.6; 95% CI, 1.2-17.2; P = .02 and hazard ratio, 13.7; 95% CI, 2.0-91.9; P = .007, respectively).

    Conclusions and Relevance: These findings indicate that discontinuation of warfarin treatment after PVI is not safe in high-risk patients, especially those who have previously experienced an ischemic stroke.

  • 42.
    Själander, Sara
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Holmqvist, Fredrik
    Smith, J. Gustav
    Platonov, Pyotr G.
    Kesek, Milos
    Svensson, Peter J.
    Blomström-Lundqvist, Carina
    Tabrizi, Fariborz
    Tapanainen, Jari
    Poci, Dritan
    Jönsson, Anders
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Oral anticoagulation after pulmonary vein isolation: a nationwide register studyManuskript (preprint) (Övrigt vetenskapligt)
  • 43.
    Själander, Sara
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Svensson, Peter J.
    Friberg, Leif
    Atrial fibrillation patients do not benefit from acetylsalicylic acid2014Ingår i: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 16, nr 5, s. 631-638Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Oral anticoagulation is the recommended treatment for stroke prevention in patients with atrial fibrillation. Notwithstanding, many patients are treated with acetylsalicylic acid (ASA) as monotherapy. Our objective was to investigate if atrial fibrillation patients benefit from ASA as monotherapy for stroke prevention. Retrospective study of patients with a clinical diagnosis of atrial fibrillation between 1 July 2005 and 1 January 2009 in the National Swedish Patient register, matched with data from the National Prescribed Drugs register. Endpoints were ischaemic stroke, thrombo-embolic event, intracranial haemorrhage, and major bleeding. The study population consisted of 115 185 patients with atrial fibrillation, of whom 58 671 were treated with ASA as monotherapy and 56 514 were without any antithrombotic treatment at baseline. Mean follow-up was 1.5 years. Treatment with ASA was associated with higher risk of ischaemic stroke and thrombo-embolic events compared with no antithrombotic treatment. Acetylsalicylic acid as monotherapy in stroke prevention of atrial fibrillation has no discernable protective effect against stroke, and may even increase the risk of ischaemic stroke in elderly patients. Thus, our data support the new European guidelines recommendation that ASA as monotherapy should not be used as stroke prevention in atrial fibrillation.

  • 44.
    Själander, Sara
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Sjögren, Vilhelm
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Renlund, Henrik
    Norrving, Bo
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Dabigatran, rivaroxaban and apixaban vs. high TTR warfarin in atrial fibrillationManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Objective: New oral anticoagulants are non-inferior compared with warfarin regarding stroke prevention in atrial fibrillation, with similar or decreased risk of bleeding. However, it is unclear whether high TTR warfarin is as effective and safe as NOACs. Our objective was to investigate efficacy and safety of apixaban, dabigatran or rivaroxaban compared with warfarin in clinical practice.

    Methods: Nationwide retrospective cohort study based on Swedish quality registries. Atrial fibrillation patients initiated on apixaban, dabigatran, rivaroxaban or warfarin between 2013-01-01 and 2015-12-31 were included. Main outcomes measures were all-cause stroke and systemic embolism, all-cause stroke, ischemic stroke, hemorrhagic stroke; major bleeding, intracranial bleeding, gastrointestinal bleeding, other bleeding (fatal or requiring hospital care); all-cause mortality; myocardial infarction.

    Results: The study included 64382 patients corresponding to 81176 treatment years. Of these, 37174 patients were instituted on warfarin, 6574 on dabigatran, 8323 on rivaroxaban and 12311 on apixaban. In warfarin treated patients, the time in therapeutic range was 71.4 %. After propensity score matching, there was no significant difference in risk of stroke or systemic embolism between NOAC and warfarin treated patients. Hazard ratios for major bleeding events were 0.63(95%CI 0.52-0.75) for apixaban, 0.74(0.62-0.87) for dabigatran and 1.06(0.92-1.23) for rivaroxaban, compared with warfarin.

    Conclusions: This study showed no difference between apixaban, dabigatran, or rivaroxaban compared to high TTR warfarin treatment regarding stroke prevention. However, fewer bleeding events were seen for apixaban and dabigatran, but not for rivaroxaban. Further studies are needed on the comparability of individual NOACs with respect to bleeding risks. 

  • 45.
    Själander, Sara
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sjögren, Vilhelm
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Renlund, Henrik
    Norrving, Bo
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Dabigatran, rivaroxaban and apixaban vs. high TTR warfarin in atrial fibrillation2018Ingår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 167, s. 113-118Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: New oral anticoagulants are non-inferior compared with warfarin regarding stroke prevention in atrial fibrillation, with similar or decreased risk of bleeding. However, it is unclear whether high TTR warfarin is as effective and safe as NOACs. Our objective was to investigate efficacy and safety of apixaban, dabigatran or rivaroxaban compared with warfarin in clinical practice.

    Materials and methods: Nationwide retrospective cohort study based on Swedish quality registries. Atrial fibrillation patients initiated on apixaban, dabigatran, rivaroxaban or warfarin between 2013-01-01 and 2015-1231 were included. Main outcome measures were all-cause stroke and systemic embolism, all-cause stroke, ischemic stroke, hemorrhagic stroke; major bleeding, intracranial bleeding, gastrointestinal bleeding, other bleeding (fatal or requiring hospital care); all-cause mortality; myocardial infarction.

    Results: The study included 64,382 patients corresponding to 81,176 treatment years. Of these, 37,174 patients were instituted on warfarin, 6574 on dabigatran, 8323 on rivaroxaban and 12,311 on apixaban. In warfarin treated patients, the time in therapeutic range was 71.4%. After propensity score matching, there was no significant difference in risk of stroke or systemic embolism between NOAC and warfarin treated patients. Hazard ratios for major bleeding events were 0.63(95% CI 0.52-0.75) for apixaban, 0.74(0.62-0.87) for dabigatran and 1.06(0.92-1.23) for rivaroxaban, compared with warfarin.

    Conclusions: This study showed no difference between apixaban, dabigatran, or rivaroxaban compared to high TTR warfarin treatment regarding stroke prevention. However, fewer bleeding events were seen for apixaban and dabigatran, but not for rivaroxaban. Further studies are needed on the comparability of individual NOACs with respect to bleeding risks.

  • 46.
    Sjögren, Vilhelm
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Byström, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Renlund, Henrik
    Svensson, Peter J.
    Oldgren, Jonas
    Norrving, Bo
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Non-vitamin K oral anticoagulants are non-inferior for stroke prevention but cause fewer major bleedings than well-managed warfarin: a retrospective register study2017Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 7, artikel-id e0181000Artikel i tidskrift (Refereegranskat)
    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.

  • 47.
    Sjögren, Vilhelm
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Grzymala-Lubanski, Bartosz
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Renlund, Henrik
    Friberg, Leif
    Lip, Gregory Y. H.
    Svensson, Peter J.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Safety and efficacy of well managed warfarin: a report from the Swedish quality register Auricula2015Ingår i: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 113, nr 6, s. 1370-1377Artikel i tidskrift (Refereegranskat)
    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.

  • 48.
    Sjögren, Vilhelm
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Grzymala-Lubanski, Bartosz
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Renlund, Henrik
    Svensson, Peter
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Safety and Efficacy of Bridging With Low-Molecular-Weight Heparin During Temporary Interruptions of Warfarin: A Register-Based Cohort Study2017Ingår i: Clinical and applied thrombosis/hemostasis, ISSN 1076-0296, E-ISSN 1938-2723, Vol. 23, nr 8, s. 961-966Artikel i tidskrift (Refereegranskat)
    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 CHADS2 (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 CHA2DS2-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.

  • 49. Soderlund, S.
    et al.
    Dahlen, T.
    Creignou, M.
    Sandin, F.
    Olsson-Stromberg, U.
    Dreimane, A.
    Markevaem, B.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Wadenvik, H.
    Stenke, L.
    Richter, J.
    Hoeglund, M.
    Progression of chronic phase chronic myeloid leukemia to advanced phase on tki therapy: A population based analysis from the Swedish CML register2015Ingår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 100, s. 233-233Artikel i tidskrift (Övrigt vetenskapligt)
  • 50. Spronk, H. M. H.
    et al.
    Padro, T.
    Siland, J. E.
    Prochaska, J. H.
    Winters, J.
    van der Wal, A. C.
    Posthuma, J. J.
    Lowe, G.
    d'Alessandro, E.
    Wenzel, P.
    Coenen, D. M.
    Reitsma, P. H.
    Ruf, W.
    van Gorp, R. H.
    Koenen, R. R.
    Vajen, T.
    Alshaikh, N. A.
    Wolberg, A. S.
    Macrae, F. L.
    Asquith, N.
    Heemskerk, J.
    Heinzmann, A.
    Moorlag, M.
    Mackman, N.
    van der Meijden, P.
    Meijers, J. C. M.
    Heestermans, M.
    Renne, T.
    Dolleman, S.
    Chayoua, W.
    Ariens, R. A. S.
    Baaten, C. C.
    Nagy, M.
    Kuliopulos, A.
    Posma, J. J.
    Harrison, P.
    Vries, M. J.
    Crijns, H. J. G. M.
    Dudink, E. A. M. P.
    Buller, H. R.
    Henskens, Y. M. C.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Zwaveling, S.
    Erkuner, O.
    Eikelboom, J. W.
    Gulpen, A.
    Peeters, F. E. C. M.
    Douxfils, J.
    Olie, R. H.
    Baglin, T.
    Leader, A.
    Schotten, U.
    Scaf, B.
    van Beusekom, H. M. M.
    Mosnier, L. O.
    van der Vorm, L.
    Declerck, P.
    Visser, M.
    Dippel, D. W. J.
    Strijbis, V. J.
    Pertiwi, K.
    ten Cate-Hoek, A. J.
    ten Cate, H.
    Atherothrombosis and Thromboembolism: Position Paper from the Second Maastricht Consensus Conference on Thrombosis2018Ingår i: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 118, nr 2, s. 229-250Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Atherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets and coagulation proteases, interacting with circulating cells and in different vascular beds, modify several complex pathologies including atherosclerosis. In the second Maastricht Consensus Conference on Thrombosis, this theme was addressed by diverse scientists from bench to bedside. All presentations were discussed with audience members and the results of these discussions were incorporated in the final document that presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following five topics:

    1. Risk factors, biomarkers and plaque instability: In atherothrombosis research, more focus on the contribution of specific risk factors like ectopic fat needs to be considered; definitions of atherothrombosis are important distinguishing different phases of disease, including plaque (in) stability; proteomic and metabolomics data are to be added to genetic information.

    2. Circulating cells including platelets and atherothrombosis: Mechanisms of leukocyte and macrophage plasticity, migration, and transformation in murine atherosclerosis need to be considered; diseasemechanism-based biomarkers need to be identified; experimental systems are needed that incorporatewhole-blood flow to understand how red blood cells influence thrombus formation and stability; knowledge on platelet heterogeneity and priming conditions needs to be translated toward the in vivo situation.

    3. Coagulation proteases, fibrin(ogen) and thrombus formation: The role of factor (F) XI in thrombosis including the lower margins of this factor related to safe and effective antithrombotic therapy needs to be established; FXI is a key regulator in linking platelets, thrombin generation, and inflammatory mechanisms in a renin-angiotensin dependent manner; however, the impact on thrombin-dependent PAR signaling needs further study; the fundamental mechanisms in FXIII biology and biochemistry and its impact on thrombus biophysical characteristics need to be explored; the interactions of red cells and fibrin formation and its consequences for thrombus formation and lysis need to be addressed. Platelet-fibrin interactions are pivotal determinants of clot formation and stability with potential therapeutic consequences.

    4. Preventive and acute treatment of atherothrombosis and arterial embolism; novel ways and tailoring? The role of protease-activated receptor (PAR)-4 vis a vis PAR-1 as target for antithrombotic therapy merits study; ongoing trials on platelet function test-based antiplatelet therapy adjustment support development of practically feasible tests; risk scores for patients with atrial fibrillation need refinement, taking new biomarkers including coagulation into account; risk scores that consider organ system differences in bleeding may have added value; all forms of oral anticoagulant treatment require better organization, including education and emergency access; laboratory testing still needs rapidly available sensitive tests with short turnaround time.

    5. Pleiotropy of coagulation proteases, thrombus resolution and ischaemia-reperfusion: Biobanks specifically for thrombus storage and analysis are needed; further studies on novelmodified activated protein C-based agents are required including its cytoprotective properties; new avenues for optimizing treatment of patients with ischaemic stroke are needed, also including novel agents that modify fibrinolytic activity (aimed at plasminogen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor.

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