Effectiveness and safety of apixaban compared to warfarin in atrial fibrillation by BMI: a non-interventional cohort study using the UK’s Clinical Practice Research Datalink (CRPD)

Abstract

Background: Current guidelines recommend starting anticoagulation therapy for patients with non-valvular atrial fibrillation (NVAF) and an increased risk of stroke. Warfarin was the anticoagulant of choice for a long period before apixaban showed superiority in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) study on the prevention of stroke/systemic embolism and bleeding. However, little is known about their effects on overweight and obese patients compared to normal weight populations, with concerns that obesity might undermine apixaban’s effects because of its fixed dosing across body mass index (BMI) groups. Methods: I emulated a target trial mirroring the ARISTOTLE study using data from the Clinical Practice Research Datalink (CPRD) linked to secondary databases. I estimated the BMI-stratum-specific hazard ratios to investigate the non-inferiority or superiority of apixaban compared to warfarin in NVAF patients in rates of a composite of stroke/systemic embolism (SE) (primary effectiveness outcome) and their individual components or superiority in major bleeding (primary safety outcome) and all-cause mortality. Results: In 51,520 patients, apixaban was non-inferior in all groups of BMI on the composite of stroke/SE with multivariable adjusted hazard ratios (HRs) of 1.11 (95% CI: 0.93, 1.32; p:0.257) in the normal weight, 1.06 (95% CI: 0.90, 1.25; p:0.459) in the overweight and 0.98 (95% CI: 0.83, 1.17; p:0.857) in the obese groups with no evidence of statistical interaction (interaction-p: 0.563). In major bleeding, apixaban was superior in normal weight (HR: 0.79; 95% CI: 0.67, 0.94; p:0.008), overweight (HR: 0.75; 95% CI: 0.64, 0.87; p:<0.001) and obese groups (HR: 0.79; 95% CI: 0.68, 0.91; p:<0.001) with no evidence of interaction (interaction-p: 0.797). Conclusion: In NVAF, BMI was not an effect modifier of the effectiveness and safety of apixaban compared to warfarin. BMI-stratum-specific estimates were consistent in overweight and obese compared to normal weight patients.