Lowering apixaban from the standard 5.0 mg twice daily dose to 2.5 mg twice daily did not significantly reduce the rates of bleeding or increase the rate of recurrent venous thromboembolism (VTE) among patients with cancer treated with anticoagulation for 6 to 12 months.
The investigator-initiated, multicenter, double-blind EVE study (ClinicalTrials.gov Identifier: NCT03080883), which was presented at the International Society of Thrombosis and Haemostasis (ISTH) 2023 Congress, randomly assigned 360 patients with cancer who completed between 6 and 12 months of anticoagulation for a confirmed VTE.
The primary endpoint was combined major bleeding plus clinically relevant nonmajor bleeding. The secondary endpoint was symptomatic VTE recurrence or arterial thromboembolism, including myocardial infarction, stroke, transient ischemic attack, or peripheral embolism.
At baseline, the mean age was 64 and 55% of patients were female. The most common thrombosis was pulmonary embolism, which had affected 58% of patients, followed by any deep vein thrombosis (DVT) among 40%, upper extremity DVT among 16%, with the remaining patients having cerebral or splanchnic venous thromboembolism. There were 74% of patients receiving active chemotherapy. Distant metastasis was present among 60% of patients, and the most common tumor types were pancreatic/hepatobiliary, colorectal, hematologic, and lung.
The rate of major plus clinically relevant non-major bleeding was similar, occurring among 8.9% of patients who received the 2.5 mg dose group compared with 12.2% of patients in the 5 mg dose group (hazard ratio [HR], 0.72; 95% CI, 0.38-1.37; P =.39). The number needed to harm was 30.
Major bleeding occurred in 2.8% and 2.2% of patient in the 2.5-mg and 5-mg dose arms (HR, 1.26; 95% CI, 0.34-4.66; P =.73) and clinically relevant non-major bleeding occurred among 6.7% and 9.9% of patients, respectively (HR, 0.66; 95% CI, 0.32-1.37; P =.26).
There was no significant difference in major bleeding at different sites, including gastrointestinal, genitourinary, intracranial, and fatal (P =.73). The rates of clinically relevant non-major bleeding were also similar at different sites (P =.26).
Robert D. McBane II, MD, of the Mayo Clinic in Rochester, MN, and the presenter of the study, noted that there appeared to be an association between bleeding occurring near the same site of the underlying malignancy.
The 2.5-mg dose of apixaban did not increase the rates of VTE recurrence. The overall rate was 5% in the 2.5-mg arm compared with 4% at the 5-mg arm (HR, 1.00; 95% CI, 0.40-2.53; P =1.0). The number needed to treat was 167. Recurrence rates were similar for pulmonary embolism, leg or arm DVT, and splanchnic or cerebral thrombosis. The rate of arterial thrombosis was also similar, occurring in 1 patient in each arm.
There were no deaths attributed to major bleeding or thromboembolism in either dose group. All-cause mortality was 15% in the 2.5-mg group and 12% in the 5-mg group (HR, 1.21; 95% CI, 0.67-2.18).
Disclosures: This research was supported by Bristol-Myers Squibb-Pfizer Alliance.
McBane RD II, et al. Extending venous thromboembolism secondary prevention with apixaban in cancer patients: EVE trial. ISTH 2023 Congress. June 24-28, 2023. Abstract LB 02.1.