Cappato, Riccardo

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.

Abstract Background Unexpected variations in treatment benefits by geographic region raise questions about the generalizability of findings from international clinical trials. Purpose Investigate the outcome of catheter ablation vs drug therapy in CABANA patients with AF treated at North American (NA) compared with non-NA sites, a pre-specified comparison. Methods CABANA randomized 2204 symptomatic patients with atrial fibrillation (AF) to ablation vs drug therapy at 126 centers in 10 countries. The primary endpoint was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Results There were 1285 patients enrolled at 85 NA sites, and 919 at 45 non-NA sites. At baseline, NA and non-NA patients differed significantly with regard to age, sex, BMI, CCS, CHA2DS2-VASc score, family history of AF, prior AF hospitalization, history of A Flutter, diabetes, NYHA class, and proportion with sleep apnea, heart disease, CAD, CHF, or EF >35%. Four-year Kaplan-Meier event rates showed considerable differences in treatment effects between NA and non-NA patients (see Table). Ablation was associated with a 50% reduction in the primary endpoint in non-NA (HR 0.50, 95% CI 0.24 to 1.03) vs a 5% reduction in NA (HR 0.95, 95% CI 0.69 to 1.30) enrollees despite higher event rates in NA patients. The trend of favorable outcome with ablation at non-NA sites was maintained after adjustment for baseline covariates that differed between the non-NA (HR 0.51, 95% CI 0.24 to 1.04) and NA populations (HR 0.93, 95% CI 0.68 to 1.20). Conclusion We observed substantial geographic variation in clinical outcomes and treatment effects in the CABANA trial that suggests an important disconnection between overall event rates and treatment benefit from ablation in AF. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): NIH