Risks and benefits of oral anticoagulants for stroke prophylaxis in atrial fibrillation according to body mass index: Nationwide cohort study of primary care records in England

Direct oral anticoagulants (DOACs) are effective and safe alternatives to warfarin for stroke prophylaxis for atrial fibrillation (AF). Whether this extends to patients at the extremes of body mass index (BMI) is unclear. Using linked primary and secondary data, Jan 1, 2010 to Nov 30, 2018, we included CHA2DS2-VASC score ≥3 in women and ≥2 in men with AF treated with oral anticoagulants (OACs). Outcomes were ischaemic stroke, major bleeding and all-cause mortality by World Health Organisation BMI classification. Patients who received warfarin were propensity score matched (1:1 ratio) with those who received DOACs and the association of time-varying OAC exposure on outcomes quantified using Cox proportional hazards models. We included 29,135 (22,818 warfarin, 6317 DOAC); 585 (2.0%) underweight, 8427 (28.9%) normal weight, 10,705 (36.7%) overweight, 5910 (20.3%) class I obesity and 3508 (12.0%) class II/III obesity. Patients treated with DOACs were older and more comorbid. After 3.7 (SD 2.5) years follow up, there was no difference in risk of ischaemic stroke and major bleeding by BMI category between DOACs and warfarin. Normal weight, overweight and obese class I patients had higher risk of all-cause mortality when treated with DOACs compared with warfarin (HR: 1.45 [95% CI 1.24–1.69], p