Apixaban thromboprophylaxis in ambulatory patients with cancer and obesity: Insights from the AVERT trial

Background: The use of direct oral anticoagulants (DOACs) in obese patients is uncertain. It is unclear if body mass index (BMI) affects the safety and efficacy of DOACs for the primary prevention of venous thromboembolism (VTE) in high-risk ambulatory patients with cancer. We sought to determine the outcomes associated with the use of apixaban for the primary prevention of cancer-associated VTE according to BMI. Methods: The randomized, double-blinded, placebo-controlled AVERT trial evaluated apixaban thromboprophylaxis in intermediate-to-high risk ambulatory cancer patients receiving chemotherapy. For this post-hoc analysis, the primary efficacy and safety outcomes were objectively confirmed VTE and clinically relevant bleeding (major and clinically relevant non-major bleeding), respectively. Obesity was defined as BMI =30 kg/m(2). Results: Among 574 patients randomized, 217 (37.8 %) patients had BMI >= 30 kg/m(2). Obese patients were overall younger, more likely to be female, had higher creatinine clearance and hemoglobin, lower platelet count, and better ECOG performance status. Compared to placebo, apixaban thromboprophylaxis was associated with reduced VTE in both obese (hazard ratio [HR] 0.26; 95 % confidence interval [CI], 0.14-0.46; p < 0.0001) and non-obese (HR 0.54; 95%CI, 0.29-1.00; p = 0.049) patients. The HR for clinically relevant bleeding (apixaban vs. placebo) was numerically higher in obese (2.09; 95%CI, 0.96-4.51; p = 0.062) than non-obese subjects (1.23; 95%CI, 0.71-2.13; p = 0.46), but overall in line with the risks observed in the general trial population. Conclusions: In the AVERT trial enrolling ambulatory cancer patients receiving chemotherapy, we found no substantial differences in the efficacy or safety of apixaban thromboprophylaxis across obese and non-obese subjects.