Background:
Obesity is a real burden and its prevalence is constantly increasing. High body weight is a risk factor for developing venous thromboembolism (VTE). Direct oral anticoagulants’ (DOAC) pharmacokinetics and pharmacodynamics are affected by obesity. Their efficacy and safety in obese (BMI ≥30kg/m
2
) and morbidly obese (BMI ≥40kg/m
2
) patients are still unclear in the treatment of VTE.
Objectives:
To compare the efficacy and safety of DOAC with vitamin K antagonist (VKA)/low molecular weight heparin (LMWH) in the acute treatment of VTE in obese and morbidly obese patients. The primary efficacy outcome was VTE recurrences. The safety outcomes were major bleeding (MB) and clinically relevant non-MB (CRNMB). All-cause mortality was also assessed.
Hypothesis:
We hypothesized that DOAC would present the same efficacy and safety for the treatment of acute VTE in obese and morbidly obese patients compared to VKA/LMWH.
Methods:
A systematic literature search (MEDLINE, EMBASE, CENTRAL, Web of Science) was conducted from inception to April 15
th
2020, identifying trials studying DOAC in the treatment of acute VTE in obese patients. Studies were included if one of the outcomes was reported. Two independent reviewers performed the study selection, data extraction, risk of bias assessment and strength of body evidence evaluation using the GRADE methodology. Analyses were conducted using the Mantel-Haenszel method based on a random-effect model. Relative risks (RR) were estimated for the effect measure with 95% confidence intervals.
Results:
From 1240 citations screened, we included 21 studies (58,590 patients). VTE recurrences was similar with DOAC compared to VKA/LMWH in obese patients (risk ratio (RR): 1.03; 95%CI 0.93-1.15; p=0.55) and morbidly obese patients (RR 1.06; 95CI 0.94-1.19; p=0.35). DOAC was associated with a reduction in MB in obese patients (RR 0.57; 95%CI 0.34-0.94; p=0.03) and morbidly obese patients (RR 0.71; 95%CI 0.50-1.00; p=0.05) compared to VKA/LMWH. In obese patients, no difference was observed in CRNMB with DOAC compared to VKA/LMWH.
Conclusion:
DOAC is as effective in reducing VTE and is associated with less MB compared to VKA/LMWH in obese and morbidly obese patients.
Comparative effectiveness and safety of direct oral anticoagulants compared to warfarin in morbidly obese patients with acute venous thromboembolism: systematic review and a meta-analysis
