Stroke Prevention in Patients With Atrial Fibrillation: A Systematic Review Update
Comparative Effectiveness Reviews, No. 214
Authors
Investigators: Gillian D. Sanders, Ph.D., Angela Lowenstern, M.D., Ethan Borre, B.A., Ranee Chatterjee, M.D., M.P.H., Adam Goode, D.P.T., Ph.D., Lauren Sharan, M.D., Nancy M. Allen LaPointe, Pharm.D., M.H.S., Giselle Raitz, M.D., Bimal Shah, M.D., M.B.A., Roshini Yapa, M.B.B.S., J. Kelly Davis, B.A., Kathryn Lallinger, M.S.L.S., Robyn Schmidt, B.A., Andrzej Kosinski, Ph.D., and Sana Al-Khatib, M.D., M.H.S.Structured Abstract
Objective:
This review updates previous reviews regarding the optimal risk stratification tools for stroke and bleeding prediction, and treatment options for stroke prevention in patients with atrial fibrillation.
Data sources:
We searched PubMed®, Embase®, and the Cochrane Database of Systematic Reviews for relevant English-language comparative studies published from January 1, 2000, to February 14, 2018.
Review methods:
Two investigators screened each abstract and full-text article for inclusion, abstracted data, rated quality and applicability, and graded evidence. When possible, random-effects models were used to compute summary estimates of effects.
Results:
Our review included 320 articles (185 unique studies). This included 61 studies relevant to predicting thromboembolic risk, 38 relevant to predicting bleeding risk, and 117 relevant to interventions for preventing thromboembolic (TE) events. Data suggest that the CHADS2, CHA2DS2-VASc, and ABC risk scores have the best evidence predicting TE risk (moderate strength of evidence [SOE] for limited prediction ability of each score) and that the HAS-BLED score has the best evidence to predict bleeding risk (moderate SOE).
We found that a thrombin inhibitor (dabigatran 150 mg) was superior to warfarin in preventing stroke (including hemorrhagic) or systemic embolism (relative risk [RR] 0.66; 95% confidence interval [CI] 0.53 to 0.82), with no statistically significant difference in the occurrence of major bleeding (RR 0.93; 95% CI 0.81 to 1.07) (high SOE for both outcomes). The Xa inhibitor apixaban was superior to warfarin in preventing stroke or systemic embolism (hazard ratio [HR] 0.79; 95% CI 0.66 to 0.95; high SOE), major bleeding (HR 0.69; 95% CI 0.60 to 0.80; high SOE), and all-cause mortality (HR 0.89; 95% CI 0.80 to 0.998; low SOE) Apixaban was also superior to aspirin in preventing stroke or systemic embolism (HR 0.45; 95% CI 0.32 to 0.62), with similar risk for major bleeding (HR 1.13; 95% CI 0.74 to 1.75) in patients who are not suitable for warfarin (moderate SOE for both outcomes). The Xa inhibitor edoxaban reduced hemorrhagic stroke and major bleeding compared to warfarin (moderate SOE for both outcomes) but had no evidence of a difference in stroke or systemic embolism (moderate SOE) or myocardial infarction (moderate SOE). The Xa inhibitor rivaroxaban was similar to warfarin in preventing stroke or systemic embolism (HR 0.88, 95% CI 0.74 to 1.03; moderate SOE), with similar rates of major bleeding (low SOE) and death (moderate SOE). Low SOE for major bleeding was due to a trend toward an increase in risk of major bleeding with rivaroxaban seen in observational studies. Comparative effectiveness findings for stroke prevention were limited by the direct comparisons between individual direct oral anticoagulants. Evidence regarding nonpharmacologic interventions was sparse, but left atrial appendage (LAA) closure devices showed a trend toward benefit over warfarin for strokes, major bleeding, and all-cause mortality that did not reach statistical significance. Higher adverse events (excessive bleeding or procedure-related complications) were observed with LAA (low SOE).
Conclusions:
Overall, we found that CHADS2, CHA2DS2-VASc, and ABC scores have similar evidence regarding their ability to predict stroke risk in patients with atrial fibrillation, whereas HAS-BLED has the best evidence to predict bleeding risk. Direct oral anticoagulants (specifically apixaban and dabigatran) demonstrate reductions in stroke events and reductions (apixaban) or similar (dabigatran) rates in bleeding events when compared with warfarin, while rivaroxaban was similar in both benefits and harms to warfarin. Edoxaban reduced hemorrhagic stroke and major bleeding compared to warfarin but had no evidence of a difference in other outcomes. More studies are needed directly comparing oral anticoagulants, including thrombin inhibitors and individual Xa inhibitors.
Suggested citation:
Sanders GD, Lowenstern A, Borre E, Chatterjee R, Goode A, Sharan L, Allen LaPointe NM, Raitz G, Shah B, Yapa R, Davis JK, Lallinger K, Schmidt R, Kosinski A, Al-Khatib S. Stroke Prevention in Patients With Atrial Fibrillation: A Systematic Review Update. Comparative Effectiveness Review No. 214. (Prepared by the Duke Evidence-based Practice Center under Contract No. 290-2015-00004-I for AHRQ and PCORI.) AHRQ Publication No. 18-EHC018-EF. PCORI Publication No. 2018-SR-04. Rockville, MD: Agency for Healthcare Research and Quality; October 2018. Posted final reports are located on the Effective Health Care Program search page. https://doi.org/10.23970/AHRQEPCCER214.
This report is based on research conducted by the Duke Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-2015-00004-I). The Patient Centered Outcomes Research Institute (PCORI) funded the report (PCORI Publication No. 2018-SR-04). The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ or PCORI. Therefore, no statement in this report should be construed as an official position of PCORI, AHRQ, or of the U.S. Department of Health and Human Services.
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