Direct oral anticoagulants in the treatment of acute venous thromboembolism in patients with obesity: A systematic review with meta-analysis

Abstract

Background: Direct oral anticoagulants' (DOAC) pharmacokinetics are affected by obesity. Their efficacy and safety in obesity (BMI≥30 kg/m²) and morbid obesity (BMI≥40 kg/m²) are still unclear in the treatment of venous thromboembolism (VTE).

Objectives: To compare the efficacy/safety of DOAC versus vitamin K antagonist (VKA)/low molecular weight heparin (LMWH) for the treatment of VTE in patients with obesity and morbid obesity. The primary efficacy/safety outcomes were VTE recurrence and major bleeding (MB). Clinically relevant non-MB and mortality were also evaluated.

Methods: A systematic literature search (MEDLINE, EMBASE, CENTRAL, Web of Science) identified studies evaluating DOAC in the treatment of VTE in patients with obesity and reporting one of the outcomes. Relative risks (RR) and 95 % confidence intervals (CI) were estimated using the Mantel-Haenszel method.

Results: We included 21 studies (50,360pts) of which 16,150 patients had a BMI≥30 kg/m² and 6443 patients had a BMI≥40 kg/m². VTE recurrence was similar with DOAC compared to VKA/LMWH in patients with obesity (RR 1.03;95 %CI 0.93-1.15;p = 0.55) and morbid obesity (RR 1.06;95 %CI 0.94-1.19;p = 0.35). DOAC were also associated with a reduction in MB (RR 0.57;95 %CI 0.34-0.94;p = 0.03 and RR 0.71;95 %CI 0.50-1.00;p = 0.05 in patients with obesity and morbid obesity, respectively). Subgroup analyses comparing randomized controlled trials to observational studies showed consistent results. No difference was observed in regards of clinically relevant non-MB and mortality.

Conclusion: There is no signal for differences in VTE recurrence in patients with obesity and morbid obesity treated with DOAC compared to VKA/LMWH, while DOAC likely reduce the risk of MB compared to VKA/LMWH.

Keywords: Body mass index; Direct oral anticoagulant; Obesity; Venous thromboembolism.