Extending Venous Thromboembolism Secondary Prevention with Apixaban in Cancer Patients. the EVE Trial.

ABSTRACTPurposeCancer-associated venous thromboembolism (VTE) management guideline recommendations include continued therapeutic anticoagulation while active cancer persists. The Federal Drug Administration label for apixaban for secondary VTE prevention includes a dose reduction to 2.5 mg twice daily after 6 months of treatment. The study purpose was to determine whether this dose reduction is advisable for cancer-associated VTE.Patients and MethodsA randomized, double-blind trial compared apixaban 2.5 mg to 5 mg twice daily for 12 months among cancer patients with VTE who had completed 6 – 12 months of anticoagulation. The primary outcome was combined major bleeding plus clinically relevant nonmajor bleeding (CRNMB).ResultsOf 370 patients recruited, 360 were included in the intention-to-treat analyses. Major plus CRNMB occurred in 16 of 179 patients (8.9%) in the apixaban 2.5 mg group compared to 22 of 181 patients (12.2%) in the 5 mg group (HR 0.72, 95% CI 0.38-1.37, p=0.39). Major bleeding occurred in 2.8% of the apixaban 2.5 mg group and 2.2% in the 5 mg group (HR 1.26, 95% CI 0.34-4.66, p=0.73). Recurrent VTE or arterial thrombosis occurred in 9 of 179 patients (5.0%) in the apixaban 2.5 mg group and 9 of 181 patients (5.0%) in the 5 mg group (HR 1.0 95% CI 0.40–2.53, p=1.00). All-cause mortality rates were similar between groups, 13% vs. 12% (HR 1.14, 95% CI 0.63–2.04; p=0.67).ConclusionFor secondary prevention of cancer associated VTE, Apixaban 2.5 mg compared to 5 mg twice daily did not lower combined bleeding events. (EVE trial. NCT03080883).