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Purpose of Review
To update a previous review in patients with atrial fibrillation/atrial flutter (AF) on the optimal risk stratification tools for stroke and bleeding prediction and on stroke prevention with current treatment options (new antithrombotic strategies, devices, and oral anticoagulants, including oral direct thrombin inhibitors and factor Xa inhibitors).
- CHADS2 and CHA2DS2-VASc scores have the best evidence to predict stroke events.
- HAS-BLED has the best evidence to predict bleeding risk.
- Imaging tools for stroke prediction require further evidence.
- Dabigatran (150mg dose) is superior to warfarin in reducing stroke with no difference in harms
- Apixaban reduces stroke, major bleeding, and all-cause mortality when compared to warfarin
- Rivaroxaban is similar to warfarin across outcomes.
- Edoxapan reduced hemorrhagic stroke and major bleeding compared to warfarin but had no difference in other outcomes.
- Further RCTs are needed directly comparing oral anticoagulants, including thrombin inhibitors and individual Xa inhibitors.
Objectives: This review updates previous reviews regarding the optimal risk stratification tools for stroke and bleeding prediction and treatment options for stroke prevention.
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 June 23, 2017.
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 285 articles (164 unique studies). This included 62 studies relevant to predicting thromboembolic risk, 34 relevant to predicting bleeding risk, and 93 relevant to interventions for preventing thromboembolic (TE) events. Data suggest that the continuous and categorical CHADS2 and continuous CHA2DS2-VASc scores have the best evidence predicting TE risk (c-statistics 0.69 [95% confidence interval (CI), 0.66 to 0.73], 0.66 [95% CI 0.63 to 0.69], and 0.67 [95% CI 0.64 to 0.705], respectively; moderate strength of evidence (SOE) for each score) and that the HAS-BLED score has the best evidence to predict bleeding risk (moderate SOE). The (ABC) tool for prediction of stroke or bleeding is promising but needs further study.
We found that a thrombin inhibitor (dabigatran 150 mg) was superior to warfarin in reducing the incidence of stroke (including hemorrhagic) or systemic embolism (relative risk [RR] 0.66; 95% CI 0.53 to 0.82), with no 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 rivaroxaban was similar to warfarin in preventing stroke or systemic embolism (moderate SOE), with similar rates of major bleeding and death (moderate SOE for both outcomes) The Xa inhibitor apixaban was superior to warfarin in reducing the incidence of 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 reducing the incidence of stroke or systemic embolism (HR 0.45; 95% CI 0.32 to 0.62), with similar hemorrhagic events, including major bleeding (HR 1.13; 95% CI 0.74 to 1.75), in patients who are not suitable for warfarin (high SOE for both outcomes). Comparative effectiveness findings for stroke prevention was limited by the direct comparisons between individual direct oral anticoagulants. Evidence regarding nonpharmacological interventions was sparse but left atrial appendage (LAA) closure devices did show a trend towards benefit over warfarin for strokes, bleeding, and all-cause mortality however with higher adverse safety events (low SOE).
Conclusions: Overall, we found that CHADS2 and CHA2DS2-VASc scores have the best evidence to predict stroke risk in patients with AF, 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. More studies are needed directly comparing oral anticoagulants including thrombin inhibitors and individual Xa inhibitors.