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Stroke prevention in atrial fibrillation
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: The Framingham Study from 1991 showed a clear correlation between atrial fibrillation (AF) and ischemic stroke, where patients with AF had an almost fivefold increase in risk of stroke compared with patients without AF. Since then, several trials have evaluated different antithrombotic treatments to reduce the risk of stroke in patients with AF. Other trials have investigated factors that increase the risk of stroke in patients with AF and risk score systems have been developed to categorize patients into low or increased risk of stroke to help clinicians to decide which patients benefit from antithrombotic treatment and in whom it can be abstained, not to expose patients with low stroke risk to an increased risk of bleeding conferred by antithrombotic treatment. The aims of this thesis were: [1] to evaluate if a warfarin dosing algorithm can increase hit rate and decrease mean error compared with manually changed doses; [2] to assess the prevalence and net clinical benefit of aspirin as monotherapy for stroke prevention in AF; [3] to investigate the risk of thromboembolic and haemorrhagic complications within 30 days after electrical cardioversion (ECV) of AF in patients with and without oral anticoagulation (OAC) pre-treatment; and [4] to assess the proportion of patients discontinuing OAC after pulmonary vein isolation (PVI), identify factors predicting stroke after PVI and to investigate risk of complications after PVI with and without OAC.

Materials and methods: All studies are retrospective and based on data from Swedish national quality registries. In paper I, data from Auricula was used to compare the resulting INR values after algorithmic warfarin dose suggestions and manually changed doses. In paper II data was extracted from the Swedish National Patient Register, the Dispensed Drugs Register and the Cause of Death Register. Patients with aspirin treatment were compared with patients without any antithrombotic treatment regarding risk of thromboembolic and haemorrhagic complications. In paper III data was collected from the Swedish National Patient Register and the Dispensed Drugs Register to examine risk of complications (thromboembolic and haemorrhagic events) within 30 days after cardioversion, comparing patients with and without oral anticoagulation pre-treatment. In paper IV data from six different Swedish national quality registries were used (Swedish Catheter Ablation Register, Auricula, Swedish National Patient Register, Dispensed Drugs Register, Cause of Death Register and Riksstroke). Patients undergoing pulmonary vein isolation (PVI) were investigated for adherence to guidelines regarding oral anticoagulation, predictors for stroke after PVI, as well as risk of ischemic stroke or intracranial haemorrhage after PVI in patients with and without treatment.

Results: Paper I showed that a computerized dosing algorithm for warfarin in most cases perform as well or better compared with doses that have been changed manually, with a better hit-rate (0.72 vs. 0.67) and a lower mean error (0.44 vs. 0.48). Paper II showed that 32% of 182.678 patients with a diagnosis of AF were on monotherapy with aspirin for stroke prevention. A total of 115.185 patients were included, 58.671 with aspirin treatment and 56.514 without antithrombotic treatment at baseline. After stratification after CHA2DS2-VASc score and after multivariable adjustment, aspirin treatment did not confer a decrease in thromboembolic events. After propensity score mathcing, rate of ischemic stroke was 7.4%/year (95% CI 7.1-7.6) in aspirin treated patients and 6.6%/year (95% CI 6.4-6.9) in patients without antithrombotic treatment. In paper III 22.874 patients undergoing electrical cardioversion were included, 10.722 with and 12.152 without OAC pre-treatment. In patients with low stroke risk (CHA2DS2-VASc 0-1), no thromboembolic complication was seen within 30 days after cardioversion. In patients with CHA2DS2-VASc ≥2, the risk of thromboembolic complications was increased when no oral anticoagulation pre-treatment was used, results that remained after propensity score matching. No difference regarding haemorrhagic complications was seen. Paper IV included a total of 1585 patients undergoing PVI with a mean follow up of 2.6 years. Adherence to current guidelines regarding oral anticoagulation was good in patients with CHA2DS2-VASc ≥2. Previous ischemic stroke was a predictor for a new stroke after PVI. In patients with CHA2DS2-VASc ≥2 stroke risk was increased in patients discontinuing OAC compared to those continuing OAC (1,60%/year vs. 0.34%/year).

Conclusion: Oral anticoagulation is still underutilized for prevention of stroke and systemic embolism in patients with atrial fibrillation. Patients with risk factors for stroke (CHA2DS2-VASc ≥2p) benefit from continuous oral anticoagulation treatment to prevent stroke, also in conjunction with electrical cardioversion and after pulmonary vein isolation. If warfarin is chosen, a computerised dosing algorithm can facilitate and standardize warfarin dosing and lead to better resulting INR values than manually changed doses. Aspirin should not be used for stroke prevention in patients with atrial fibrillation.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet , 2016. , 96 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1823
Keyword [en]
Atrial fibrillation, stroke, oral anticoagulation, aspirin, haemorrhage, electrical cardioversion, pulmonary vein isolation
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
URN: urn:nbn:se:umu:diva-124951ISBN: 978-91-7601-519-3OAI: oai:DiVA.org:umu-124951DiVA: diva2:956883
Public defence
2016-09-23, Aulan, Sundsvalls sjukhus, Sundsvall, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2016-09-02 Created: 2016-08-31 Last updated: 2016-09-05Bibliographically approved
List of papers
1. Computer aided warfarin dosing in the Swedish national quality registry AuriculA: algorithmic suggestions are performing better than manually changed doses
Open this publication in new window or tab >>Computer aided warfarin dosing in the Swedish national quality registry AuriculA: algorithmic suggestions are performing better than manually changed doses
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2013 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 131, no 2, 130-134 p.Article in journal (Refereed) Published
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.

Keyword
Anticoagulation, Atrial fibrillation, Computer-assisted therapy, INR, Warfarin
National Category
Cardiac and Cardiovascular Systems Hematology
Identifiers
urn:nbn:se:umu:diva-66123 (URN)10.1016/j.thromres.2012.11.016 (DOI)000313719400009 ()23232091 (PubMedID)
External cooperation:
Available from: 2013-02-15 Created: 2013-02-15 Last updated: 2016-09-01Bibliographically approved
2. Atrial fibrillation patients do not benefit from acetylsalicylic acid
Open this publication in new window or tab >>Atrial fibrillation patients do not benefit from acetylsalicylic acid
2014 (English)In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 16, no 5, 631-638 p.Article in journal (Refereed) Published
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.

Keyword
Atrial fibrillation, Stroke, Acetylsalicylic acid
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-90440 (URN)10.1093/europace/eut333 (DOI)000336080400006 ()
External cooperation:
Available from: 2014-07-09 Created: 2014-06-23 Last updated: 2016-09-01Bibliographically approved
3. Atrial fibrillation patients with CHA2DS2-VASc > 1 benefit from oral anticoagulation prior to cardioversion
Open this publication in new window or tab >>Atrial fibrillation patients with CHA2DS2-VASc > 1 benefit from oral anticoagulation prior to cardioversion
2016 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 215, 360-363 p.Article in journal (Refereed) Published
Abstract [en]

Background: Electrical cardioversion of atrial fibrillation is associated with an increased risk of embolic stroke, but is generally considered safe if performed within 48 h after onset. Our objective was to investigate if thromboembolism and bleeding in association with cardioversion of atrial fibrillation differed between patients with and without oral anticoagulation.

Methods: Retrospective study of patients with atrial fibrillation undergoing electrical cardioversion from national Swedish health registries from January 1st 2006 until December 1st 2010. Main outcome measures were thromboembolism and bleeding.

Results: In total 22,874 atrial fibrillation patients underwent electrical cardioversion, 10,722 with and 12,152 without oral anticoagulation pre-treatment. Patients with low stroke risk (CHA(2)DS(2)-VASc 0-1) did not suffer from any thromboembolic complications within 30 days after cardioversion. After adjustment for factors included in CHA(2)DS(2)-VASc and after propensity score matching, patients without oral anticoagulation had higher risk for thromboembolic complications, odds ratio 2.54 (95% confidence interval 1.70-3.79) and odds ratio 2.51 (95% confidence interval 1.69-3.75). There were no significant differences regarding bleeding complications between patients with or without anticoagulation after adjustment for factors included in HAS-BLED, odds ratio 1.08 (95% confidence interval 0.51-2.25), nor after propensity score matching, odds ratio 1.00 (95% confidence interval 0.48-2.10).

Conclusion: The results suggest that electrical cardioversion without prior anticoagulation may not be safe for patients with risk factors for thromboembolism (CHA(2)DS(2)-VASc score >1 point).

Keyword
Atrial fibrillation, Thromboembolism, Electrical cardioversion, Oral anticoagulation
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-122543 (URN)10.1016/j.ijcard.2016.04.031 (DOI)000376297100079 ()27128562 (PubMedID)
External cooperation:
Available from: 2016-07-27 Created: 2016-06-20 Last updated: 2016-09-01Bibliographically approved
4. Oral anticoagulation after pulmonary vein isolation: a nationwide register study
Open this publication in new window or tab >>Oral anticoagulation after pulmonary vein isolation: a nationwide register study
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(English)Manuscript (preprint) (Other academic)
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-124946 (URN)
External cooperation:
Available from: 2016-08-31 Created: 2016-08-31 Last updated: 2016-09-01

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