Direct oral anticoagulants, all-cause mortality and cardiovascular events in patients with atrial fibrillation with and without obesity: a sub-analysis of the nationwide START registry.

Abstract Introduction Atrial fibrillation (AF) was often associated with cardiovascular comorbidities, such as obesity. Direct oral anticoagulants (DOACs) use in patients with AF and obesity is still uncertain for the low number of obese patients enrolled in clinical trial and for peculiar pharmacokinetic characteristics of obese patients. We compared the all-cause mortality and cardiovascular events (CVEs) risk in obese patients with AF treated with DOAC or warfarin. Methods 10.369 AF patients on oral anticoagulants were enrolled in the multicenter nationwide START registry. Obesity was defined as body mass index (BMI) ≥30 Kg/m2. 1st degree obesity was defined by a BMI between 30 and 34.9 Kg/m2, while ≥2nd degree was defined if BMI was ≥35 Kg/m2. The association between DOACs use, all-cause mortality and CVEs was investigated with Cox regression analysis to estimate hazard ratio (HR) and 95% confidence interval (95%CI). Results Mean age was 76.3±9.4 and 45.3% were women. 3,725 (35.9%) patients were overweight and 2,240 (21.6%) were obese. Obese patients were more frequently affected by arterial hypertension, diabetes, anemia, heart failure, and chronic lung disease. During a mean follow up was 23.9±19 months, 704 deaths and 821 CVEs occurred. In obese patients, elderly (HR 2.460, 95% 1.690-3.583, p0.001), anemia (HR 1.514, 95%CI 1.045-2.192, p=0.028), cerebrovascular disease history (HR 1.614, 95%CI 1.056-2.467, p=0.027), peripheral artery disease (PAD) (HR 2.204, 95%CI 1.278-3.800, p= 0.004) and heart failure (HF) (HR 1.769, 95%CI 1.220-2.563, p= 0.003) were associated with higher risk of all-cause mortality, while, among treatment, only DOAC use was associated with a lower mortality risk (HR 0.637, 95%CI 0.445-0.912, p= 0.014). Elderly 8HR 2.102, 95%CI 1.501-2.943, p0.001), anemia (HR 1.440, 95%CI 1.019-2.036, p= 0.039), cerebrovascular disease history (HR 1.707, 95%CI 1.160-2.512, p=0.007), PAD (HR 1.931, 95%CI 1.147-3.250, p= 0.013) and HF (HR 1.562, 95%CI 1.105-2.208, p= 0.012) were also associated with higher risk of CVEs, while DOAC treatment was not associated with a reduction of CVE in obese patients (HR 0.751, 95%CI 0.542-1.041, p=0.086). DOAC use (vs warfarin) was associated with a both reduction in all-cause mortality and CVEs in patients with normal weight (HR 0.473, 95%CI 0.367-0.609, p0.001 and HR 0.658, 95%CI 0.525-0.824, p0.001, respectively) and overweight (HR 0.471, 95%CI 0.360-0.617, p0.001 and HR 0.616, 95%CI 0.486-0.791, p0.001, respectively). DOAC use was also associated with a reduction in all-cause mortality (HR 0.640, 95%CI 0.428-0.957, p= 0.030) but not CVEs (HR 0.822, 95%CI 0.575-1.175, p= 0.282) in patients with first degree obesity. No difference between DOAC and VKA users was observed in patients with at least second degree of obesity. Conclusion DOAC use seems to be associated with a lower risk of all cause-mortality but not CVEs in obese AF patients, further study, especially on severe obesity are needed.