Impact of concurrent antiplatelet use on the safety and efficacy of thromboprophylaxis with apixaban in patients with cancer: A post-hoc analysis of the AVERT trial

BACKGROUND: Data on bleeding risk from combining prophylactic anticoagulation with drugs that have antiplatelet properties (antiplatelet agents or nonsteroidal anti-inflammatory drugs (NSAIDs)) in patients with active cancer are limited. We evaluated the impact of concurrent antiplatelet/NSAID use on the safety and efficacy of apixaban thromboprophylaxis in ambulatory cancer patients. METHODS: This post-hoc analysis of the AVERT trial assessed clinically relevant bleeding (major plus clinically relevant non-major bleeding [CRNMB]) as the primary outcome. Secondary outcomes included major VTE, major bleeding, CRNMB, and all-cause mortality. Hazard ratios (HRs) were estimated using Cox models adjusted for age, sex, and center. Subgroup analyses examined antiplatelet agents (aspirin or clopidogrel) and NSAIDs separately. RESULTS: Among 563 included patients, 184 used drugs with antiplatelet properties (apixaban n = 99; placebo n = 85) and 379 did not. In the apixaban arm, concurrent use of these drugs increased clinically relevant bleeding (HR 1.80; 95% CI 1.15-2.82) and CRNMB (HR 2.01; 95% CI 1.21-3.34) without reducing VTE (HR 0.61; 95% CI 0.26-1.45). Among antiplatelet users (n = 61), risks of clinically relevant bleeding (HR 2.02; 95% CI 1.29-3.18) and CRNMB (HR 2.63; 95% CI 1.59-4.35) were higher. NSAID users (n = 42) showed no significant differences in bleeding outcomes. In the placebo arm, concurrent use was not associated with increased clinically relevant bleeding but was linked to more CRNMB (HR 1.88; 95% CI 1.00-3.55). No impact on all-cause mortality was observed. CONCLUSIONS: Concurrent use of antiplatelet drugs during apixaban thromboprophylaxis in cancer patients increases clinically relevant bleeding without reducing VTE.