| 1. |
- Björck, Fredrik, et al.
(författare)
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Warfarin persistence among stroke patients with atrial fibrillation
- 2015
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Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 136:4, s. 744-748
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Warfarin treatment discontinuation is significant among patients with atrial fibrillation (AF). For AF patients with stroke a warfarin persistence rate of 0.45 after 2 years has previously been reported. No consistent predictors for discontinuation have been established. Aims: Evaluation of warfarin persistence and variables associated with discontinuation, in a large Swedish cohort with unselected stroke/TIA patients with AF treated with warfarin. Materials and methods: 4 583 patients with stroke/TIA and AF in the Swedish National Patient Register (NPR), from 1. Jan 2006 to 31. Dec 2011, were matched with the Swedish national quality register AuriculA. They were followed until treatment cessation, death or end of study. Baseline characteristics and CHA(2)DS(2)VASc score were retrieved from NPR. Treatment-time was retrieved from AuriculA. Results: Overall proportion of warfarin persistence was 0.78 (95% confidence interval (CI) 0.76 to 0.80) after one year, 0.69 (95% CI 0.67 to 0.71) after 2 years and 0.47 (95% CI 0.43 to 0.51) after 5 years. Variables clearly associated with higher discontinuation were dementia (hazard ratio (HR) 2.22, CI 1.51-3.27) and alcohol abuse (HR 1.66, CI 1.19-2.33). Chronic obstructive pulmonary disease (COPD), cancer and chronic heart failure (CHF) were each associated with over 20% increased risk of treatment discontinuation. Higher CHA(2)DS(2)VASc score and start-age lead to lower persistence (p < 0.001). Conclusions: Persistence to warfarin in unselected stroke/TIA patients with AF is in Sweden greater than previously reported. Lower persistence is found among patients with high treatment start-age, incidence of dementia, alcohol abuse, cancer, CHF, COPD and/or high CHA(2)DS(2)VASc score.
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| 2. |
- Sandén, Per, et al.
(författare)
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Venous thromboembolism and cancer risk
- 2017
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 43:1, s. 68-73
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Björck, Fredrik, 1974-, et al.
(författare)
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Predictors for INR-control in a well-managed warfarin treatment setting
- 2019
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer. - 0929-5305 .- 1573-742X. ; 47:2, s. 227-232
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 4. |
- Björck, Fredrik, et al.
(författare)
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Warfarin persistence among atrial fibrillation patients – why is treatment ended?
- 2016
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Ingår i: Cardiovascular Therapeutics. - : Wiley. - 1755-5914. ; 34:6, s. 468-474
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Tidskriftsartikel (refereegranskat)abstract
- Background and AimWarfarin 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.MethodsFrom 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.ResultsProportion 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.ConclusionsAlthough 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.
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| 5. |
- Björck, Fredrik, 1974-
(författare)
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Warfarin treatment quality in stroke prevention
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundIschemic stroke is a serious condition often associated to presence of atrial fibrillation (AF). Use of anticoagulants for AF patients greatly reduces the risk of stroke. Warfarin is the most commonly used anticoagulant in Sweden. The aim of this thesis was to study the impact of warfarin treatment quality in Swedish stroke prevention.MethodsStudy I, II and IV were relatively large multicentre, retrospective, cohort studies based on Swedish registries, especially AuriculA, a quality register for AF and anticoagulation. Background data as well as bleeding and thromboembolic complications were retrieved from the National Patient Register. The Cause of Death Register was used in study II and IV. The Swedish Prescribed Drug Register was used in study IV, for data on concomitant acetylsalicylic acid (ASA) use. Study period was January 1, 2006, to December 31, 2011. Study III enrolled all warfarin treated AF patients in Sundsvall, registered in AuriculA on January 1, 2010. This smaller cohort was followed until discontinuation or study-stop December 31, 2013. All used data were collected from each patient’s medical record.ResultsThe annual risk of major bleedings and thromboembolic events for warfarin treated patients, including all different indications for warfarin, was relatively low (2.24% and 2.66%), with incidence of intracranial bleeding of 0.37% per treatment year. The overall mean time in therapeutic range (TTR) was 76.5%. Patients started on warfarin due to AF had a mean TTR of 68.6%, with an annual risk of major bleeding and thromboembolic events of 2.23% and 2.95%, and with 0.44% annual risk of intracranial bleeding. No significant differences in overall complications were found when comparing treatment monitored in anticoagulation clinics (ACC) with treatment monitored in primary health care centers (PHCC). There were significantly increased risk of both overall major bleedings and thromboembolic events for those warfarin treated AF patients receiving additional ASA treatment, having individual TTR (iTTR) below 70%, or having high international normalized ratio (INR) variability. AF patients with low INR variability had generally lower complication rates, compared with patients with high INR variability. There were however no alteration on cumulative incidence of complications due to INR variability, for AF patients with iTTR ≥70%. The overall proportion of persistence to warfarin treatment for stroke patients with AF was found to be 0.69 after 2 years treatment and 0.47 after 5 years. Stroke patients with diagnosed dementia at baseline were more than two-times likely of discontinuing warfarin than others. Excessive alcohol use, chronic obstructive pulmonary disease, cancer and chronic heart failure were baseline diagnoses each associated with over 20% increased risk of treatment discontinuation. Lower persistence to treatment was linked to increasing start-age and CHA2DS2-VASc scores. As documented reasons for warfarin treatment discontinuation in AF patients, we found regained sinus rhythm as the most common addressed cause (31.2%), followed by problematic monitoring and bleedings. We estimated that only half (49.5%) of the treatment discontinuations were clinically well motivated.ConclusionsQuality of Swedish warfarin treatment in initiated stroke prevention is high, with generally low rates of complications and high TTRs, no matter treatment in ACC or PHCC, including high long time persistence to warfarin in secondary stroke prevention. For better outcome in future warfarin stroke prophylactic treatment clinicians should aim for iTTRs above 70%, avoid additional ASA therapy, support fragile patients like those with excessive alcohol use and dementia, and base decisions on treatment discontinuations on solid medical arguments.
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| 6. |
- Björck, Fredrik, et al.
(författare)
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Warfarin treatment quality is consistently high in both anticoagulation clinics and primary care setting in Sweden
- 2015
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Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 136:2, s. 216-220
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Dahlén, Torsten, et al.
(författare)
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Adverse outcomes in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors : Follow-up of patients diagnosed 2002-2017 in a complete coverage and nationwide agnostic register study
- 2022
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Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 97:4, s. 421-430
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Tidskriftsartikel (refereegranskat)abstract
- Tyrosine kinase inhibitors (TKIs) have profoundly improved the clinical outcome for patients with chronic myeloid leukemia (CML), but their overall survival is still subnormal and the treatment is associated with adverse events. In a large cohort-study, we assessed the morbidity in 1328 Swedish CML chronic phase patients diagnosed 2002-2017 and treated with TKIs, as compared to that in carefully matched control individuals. Several Swedish patient registers with near-complete nationwide coverage were utilized for data acquisition. Median follow-up was 6 (IQR, 3-10) years with a total follow-up of 8510 person-years for the full cohort. Among 670 analyzed disease categories, the patient cohort showed a significantly increased risk in 142 while, strikingly, no category was more common in controls. Increased incidence rate ratios/IRR (95% CI) for more severe events among patients included acute myocardial infarction (AMI) 2.0 (1.5-2.6), heart failure 2.6 (2.2-3.2), pneumonia 2.8 (2.3-3.5), and unspecified sepsis 3.5 (2.6-4.7). When comparing patients on 2nd generation TKIs vs. imatinib in a within-cohort analysis, nilotinib generated elevated IRRs for AMI (2.9; 1.5-5.6) and chronic ischemic heart disease (2.2; 1.2-3.9), dasatinib for pleural effusion (11.6; 7.6-17.7) and infectious complications, for example, acute upper respiratory infections (3.0; 1.4-6.0). Our extensive real-world data reveal significant risk increases of severe morbidity in TKI-treated CML patients, as compared to matched controls, particularly for 2nd generation TKIs. Whether this increased morbidity may also translate into increased mortality, thus preventing CML patients to achieve a normalized overall survival, needs to be further explored.
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| 8. |
- Enblom-Larsson, Anneli, et al.
(författare)
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Thromboembolic events, major bleeding and mortality in essential thrombocythaemia and polycythaemia vera : a matched nationwide population-based study
- 2024
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Ingår i: British Journal of Haematology. - : John Wiley & Sons. - 0007-1048 .- 1365-2141. ; 204:5, s. 1740-1751
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Tidskriftsartikel (refereegranskat)abstract
- Thromboembolic events and bleeding are known complications in essential thrombocythaemia (ET) and polycythaemia vera (PV). Using multiple Swedish health care registers, we assessed the rate of arterial and venous events, major bleeding, all-cause stroke and all-cause mortality in ET and PV compared to matched controls. For each patient with ET (n = 3141) and PV (n = 2604), five matched controls were randomly selected. In total, 327 and 405 arterial or venous events were seen in the group of ET and PV patients respectively. Compared to corresponding controls, the rate of venous thromboembolism, major bleeding and all-cause mortality per 100 treatment years was significantly increased among both ET (0.63, 0.79 and 3.70) and PV patients (0.94, 1.20 and 4.80). The PV patients also displayed a significantly higher rate of arterial events and all-cause stroke compared to controls. When dividing the cohort into age groups, we found a significantly higher rate of arterial and venous events in all age groups of PV patients, and the rate of all-cause mortality was significantly higher in both ET and PV patients in all ages above the age of 50. This study confirms that PV and ET are diseases truly marked by thromboembolic complications and bleeding.
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| 9. |
- Grzymala-Lubanski, Bartosz, et al.
(författare)
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Computer aided warfarin dosing in the Swedish national quality registry AuriculA : algorithmic suggestions are performing better than manually changed doses
- 2013
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Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 131:2, s. 130-134
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 10. |
- Labaf, Ashkan, et al.
(författare)
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INR variability and outcomes in patients with mechanical heart valve prosthesis
- 2015
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Ingår i: Thrombosis Research. - : Elsevier. - 0049-3848 .- 1879-2472. ; 136:6, s. 1211-1215
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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