Superior Safety and Efficacy of Doacs over Warfarin in Obese Patients: A Propensity-Matched Cohort Study

Background: Prior studies on acute venous thromboembolism (VTE) and non-valvular atrial fibrillation (AF) have shown that direct oral anticoagulants (DOACs) offer similar or superior efficacy and reduced bleeding risks compared to warfarin for patients with VTE and cardiac arrhythmias. However, these studies have not extensively included morbidly obese individuals (BMI ≥ 40 kg/m²), leaving a gap in knowledge regarding the safety and effectiveness of DOACs compared to warfarin in this group. This research aims to assess the performance and safety of the direct oral factor Xa inhibitors, apixaban and rivaroxaban, relative to warfarin in morbidly obese patients.

Methods: A retrospective cohort study was performed using the TriNetX US Collaborative Network, involving 189,175 patients on DOACs and 117,487 patients on warfarin. Propensity score matching was applied, resulting in two cohorts of 82,502 patients each. The study measured key outcomes such as mortality, recurrent VTE, major bleeding, any bleeding, and incident stroke. For each outcome, incidence rates per 100 person-years, hazard ratios (HR), and p-values were computed.

Results: The mean age of the patients in both the DOACs and warfarin cohorts was 64.9 years after matching. Gender distribution was similar between the cohorts, with the DOACs cohort consisting of 56.8% females and 39.3% males, and the warfarin cohort comprising 57.5% females and 40.2% males. In terms of race and ethnicity, 17.0% of the DOACs cohort were Black or African American, 71.2% were White, and 3.7% were Hispanic or Latino. For the warfarin cohort, 17.3% were Black or African American, 70.1% were White, and 4.0% were Hispanic or Latino. The incidence rates per 100 person-years showed lower mortality in the DOACs cohort compared to the warfarin cohort (6.65 vs 9.08), with a hazard ratio (HR) of 0.734 (95% CI: 0.705-0.763, p=0.001). The incidence of recurrent VTE was lower in the DOACs cohort compared to the warfarin cohort (4.68 vs 6.89), with an HR of 0.674 (95% CI: 0.642-0.709, p=0.012). Major bleeding rates were lower in the DOACs cohort (3.33 vs 4.94), with an HR of 0.671 (95% CI: 0.635-0.708, p<0.001). Overall bleeding rates were significantly lower in the DOACs cohort (7.49 vs 13.87), with an HR of 0.526 (95% CI: 0.508-0.544, p<0.001). The incidence of incident stroke was lower in the DOACs cohort (6.09 vs 9.41), with an HR of 0.640 (95% CI: 0.615-0.666, p<0.001).

Conclusions: In morbidly obese patients, DOACs use resulted in significantly lower rates of mortality, recurrent VTE, major bleeding, overall bleeding, and incident stroke compared to warfarin. These results indicate that DOACs may be a safer and more effective anticoagulation option for morbidly obese individuals. Further prospective studies with detailed data on comorbidities, cancer diagnosis, pharmacogenetics, thrombophilia, compliance, and target therapeutic INR achievement are recommended to validate these findings.