Abstract

OBJECTIVES: This study evaluated the comparative effectiveness of vitamin K antagonists (VKAs), direct thrombin inhibitors (DTIs) and factor Xa inhibitors (FXaI) in patients with atrial fibrillation (AF) at risk of stroke in everyday practice. METHODS: Data from patients with AF and Congestive heart failure, Hypertension, Age 75 years, Diabetes mellitus, prior Stroke, TIA, or thromboembolism, Vascular disease, Age 65-74 years, Sex category (CHA2DS2-VASc) score ≥2 (excluding gender) in the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation registry were analysed using an improved method of propensity weighting, overlap weights and Cox proportional hazards models. RESULTS: All-cause mortality, non-haemorrhagic stroke/systemic embolism (SE) and major bleeding over 2 years were compared in 25 551 patients, 7162 (28.0%) not treated with oral anticoagulant (OAC) and 18 389 (72.0%) treated with OAC (FXaI (41.8%), DTI (11.4%) and VKA (46.8%)). OAC treatment compared with no OAC treatment was associated with decreased risk of all-cause mortality (HR 0.82 (95% CI 0.74 to 0.91)) and non-haemorrhagic stroke/SE (HR 0.71 (95% CI 0.57 to 0.88)) but increased risk of major bleeding (HR 1.46 (95% CI 1.15 to 1.86)). Non-vitamin K antagonist oral anticoagulant (NOAC) use compared with no OAC treatment was associated with lower risks of all-cause mortality and non-haemorrhagic stroke/SE (HR 0.67 (95% CI 0.59 to 0.77)) and 0.65 (95% CI 0.50 to 0.86)) respectively, with no increase in major bleeding (HR 1.10 (95% CI 0.82 to 1.47)). NOAC use compared with VKA use was associated with lower risk of all-cause mortality and major bleeding (rates/100 patient-years 3.6 (95% CI 3.3 to 3.9) vs 4.8 (95% CI 4.5 to 5.2) and 1.0 (95% CI 0.9 to 1.1) vs 1.4 (95% CI 1.2 to 1.6); HR 0.79 (95% CI 0.70 to 0.89) and 0.77 (95% CI 0.61 to 0.98) respectively), with similar risk of non-haemorrhagic stroke/SE (rates/100 patient-years 0.8 (95% CI 0.7 to 0.9) versus 1.0 (95% CI 0.8 to 1.1); HR 0.96 (95% CI 0.73 to 1.25). CONCLUSION: Important benefits in terms of mortality and major bleeding were observed with NOAC versus VKA with no difference among NOAC subtypes. TRIAL REGISTRATION NUMBER: NCT01090362.