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

Abstract

Direct oral anticoagulant (DOAC) agents are becoming the anticoagulation strategy of choice. However, their use in the treatment of acute venous thromboembolism (VTE) in morbidly obese patients (bodyweight of > 120 kg or BMI > 40 kg/ m 2) guarded. This is due to the scarce data supporting their use in this population. As a result, the International Society on Thrombosis and Haemostasis recommended against their use in this cohort of patients. New data emerged supporting the use of DOACs in these patients. Hence, we aimed to systematically review the literature exploring the efficacy and safety of these agents compared to warfarin in VTE treatment in morbidly obese patients. A systematic review of PubMed and EMBASE since inception until 01/04/2020. Subsequently, a non-inferiority (NI of 1.75) meta-analysis utilizing the random-effects model. Five observational studies (6585 patients) were included in our meta-analysis. DOAC analogs were non-inferior compared to warfarin in reducing the primary efficacy outcome of VTE recurrence (OR 1.07, 95% CI 0.93-1.23) and the primary safety outcome (major bleeding events) (OR 0.80, 95% CI 0.54-1.17). Our meta-analysis comprising real-world observational data concludes that the use of DOAC analogs in morbidly obese patients (bodyweight of > 120 kg or BMI > 40 kg/m 2) is non-inferior with regards to efficacy and safety compared to warfarin. This finding helps to resolve the uncertainty associated with the use of DOACs in this cohort. Additionally, it invites for a confirmatory non-inferiority randomized controlled trial testing DOAC vs. Warfarin in this group of patients.

A review of indications and comorbidities in which warfarin may be the preferred oral anticoagulant

“…Clinical outcomes associated with DOACs in obese patients remain to be elucidated in RCTs. To date, four published systematic reviews and meta‐analyses provide insight into this population 48‐50 . Most studies in these reviews were retrospective observational analyses of patients with body mass index (BMI) >40 kg/m 2 or weight >120 kg and included rivaroxaban or apixaban 48 .…”

“…Most studies in these reviews were retrospective observational analyses of patients with body mass index (BMI) >40 kg/m 2 or weight >120 kg and included rivaroxaban or apixaban 48 . Overall, retrospective cohorts of AF and VTE identified no significant differences between specific DOACs and warfarin for thromboembolism or major bleeding events 48,49,51 . One post hoc analysis of the ARISTOTLE trial found that, compared to warfarin, apixaban was associated with a lower rate of SSE in patients with BMI 35–40 kg/m 2 (HR 0.31, 95% CI 0.13–0.74) and lower rates of major bleeding in BMI 25–30 kg/m 2 (HR 0.73, 95% CI 0.57–0.92).…”

“…To date, four published systematic reviews and meta-analyses provide insight into this population. [48][49][50] Most studies in these reviews were retrospective observational analyses of patients with body mass index (BMI) >40 kg/m 2 or weight >120 kg and included rivaroxaban or apixaban. 48 Overall, retrospective cohorts of AF and VTE identified no significant differences between specific DOACs and warfarin for thromboembolism or major bleeding events.…”

“…48 Overall, retrospective cohorts of AF and VTE identified no significant differences between specific DOACs and warfarin for thromboembolism or major bleeding events. 48,49,51…”

Direct Oral Anticoagulants in the Treatment of Venous Thromboembolism: Use in Patients with Advanced Renal Impairment, Obesity, or Other Weight-Related Special Populations

“…A meta-analysis of these five observational studies that specifically evaluated patients with VTE and a BMI greater than 40 kg/m 2 or a weight greater than 120 kg (n ¼ 6585) has been published. 93 There was no difference in the primary efficacy endpoint of recurrent VTE (odds ratio [OR]: 1.07, 95% CI: 0.93-1.23) or in the primary safety endpoint of major bleeding (OR: 0.80, 95% CI: 0.54-1.17). It should be noted that 88% of the patients in the meta-analysis come from the study by Spyropoulos and colleagues, and the majority of the DOAC use was rivaroxaban followed by apixaban.…”