Obese patients with atrial fibrillation are more efficiently protected from thrombosis under warfarin or xabans compared to non-obese patients; a systematic review and Meta-analysis of six randomized controlled trials.

INTRODUCTION: Recommendations about proper anticoagulation in obese patients, body mass index (BMI) > 30 kg/m2, are not yet clearly defined. Obese patients were included in randomized controlled trials comparing new anticoagulants (NOACs) with warfarin in patients with atrial fibrillation or thromboembolism. METHODS: We performed a medline search entering proper criteria and finally 6 post-hoc analysis of RCTs, reporting outcome according to BMI, were included in this meta-analysis. Two major outcomes were considered end points in our meta-analysis; thrombosis, including ischemic cerebral events (transient or not) and venous thrombosis (DVD) /pulmonary embolism (PE) and bleeding, including major bleeding and clinically relevant non-major bleeding. RESULTS: In the NOACs treated group, thrombosis occurred less frequently in obese vs non-obese patients; RR and 95 % CI 0,75 (0,58-0,97), p = 0,03, while low heterogeneity was observed (I2= 40 %). In the warfarin treated subgroup there was statistically significant difference with less thrombotic events occurring in the obese vs non-obese patients; RR and (95 % CI) 0,80 (0,66-0,98), p = 0,03, and heterogeneity was low (I2 = 24 %). This protective effect called the obesity paradox is limited to obese patients anticoagulated for non-valvular atrial fibrillation (NVAF); RR (95 % CI) was 0,70 (0,58-0,85) p = 0,03 and I2 = 24 %. Bleeding events were similar under both NOACs and warfarin in obese vs non-obese analysis. CONCLUSIONS: Obese patients anticoagulated for NVAF with either standard dose of xabans or INR guided warfarin are more efficiently protected against thrombosis compared to non-obese patients.

Apixaban reduces the risk of major and clinically relevant non-major bleeding compared to warfarin in patients with end stage renal disease; a systematic review and meta-analysis of ten studies.

Optimal anticoagulation in patients with end-stage renal disease ESRD is a matter of debate since these patients are not included in randomized controlled trials (RCTs). Evolving data are in favor of apixaban compared to warfarin. METHODS: We extracted data from 2 RCTs, 5 retrospective cohort studies and 3 large data-based studies. Both dosing regimens of apixaban, standard or reduced, were accepted. In most studies characteristics of patients were balanced between arms. Patients with either atrial fibrillation (AF) or venous thromboembolism (VTE) were included. Quality of studies was graded as high and the funnel plot did not detect any publication bias. In total we analyzed the outcome of 6693 ESRD patients treated with apixaban and 19,836 treated with warfarin. Our analysis was performed by using the random effects model. We report our data as Risk Ratio (RR) and associated 95 % confidence interval values (95 %, CI). RESULTS: The RR (95 % CI) of major bleeding was 0.69 (0.57-0.84) p = 0.0002 in favor of apixaban vs warfarin with heterogeneity to be statistically significant I2 63% p = 0.004. Meta-regression analysis with year of publication as moderator shows in bubble plotting that studies published earlier than 2018 were plotted as outliers. The RR (95 % CI) of clinically relevant non-major bleeding (CRNMB) was 0.74 (0.64-0.87) p = 0.0002 favoring again apixaban. Standard apixaban dose over reduced dose is less hemorrhagic compared to warfarin. Overall, in our study the risk of thrombosis in both arms was statistically non-different. CONCLUSIONS: In our study we observed less hemorrhagic events with apixaban in ESRD patients compared to warfarin.