Apixaban for Extended Treatment of Provoked Venous Thromboembolism

Abstract

Background: The appropriate duration of anticoagulation for venous thromboembolism (VTE) in patients who have a transient provoking factor (e.g., surgery, trauma, or immobility) and concomitant enduring risk factors is uncertain.

Methods: In this single-center, double-blind, randomized trial, adults with VTE after the occurrence of a transient provoking factor who had at least one enduring risk factor and had completed at least 3 months of anticoagulation were assigned to receive oral apixaban (at a dose of 2.5 mg twice daily) or placebo for 12 months. The primary efficacy outcome was the first symptomatic recurrent VTE. The primary safety outcome was the first episode of major bleeding according to the criteria of the International Society on Thrombosis and Hemostasis.

Results: A total of 600 patients underwent randomization (mean age, 59.5 years; female sex, 57.0%; non-White race, 19.2%). The trial population had a broad range of provoking factors and enduring risk factors. Symptomatic recurrent VTE occurred in 4 of the 300 patients (1.3%) in the apixaban group and in 30 of the 300 patients (10.0%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.04 to 0.36; P<0.001). Major bleeding occurred in 1 patient in the apixaban group and none in the placebo group. Clinically relevant nonmajor bleeding was observed in 14 of 294 patients (4.8%) in the apixaban group and in 5 of 294 patients (1.7%) in the placebo group (hazard ratio, 2.68; 95% CI, 0.96 to 7.43; P = 0.06). One patient in the apixaban group and 3 patients in the placebo group died, with no deaths attributed to cardiovascular or hemorrhagic causes. Nonhemorrhagic, nonfatal adverse events occurred in 6 patients (2.0%) in each group.

Conclusions: Among patients with provoked VTE and enduring risk factors, low-intensity therapy with apixaban for 12 months resulted in a lower risk of symptomatic recurrent VTE than placebo, with a low risk of major bleeding. (Funded by Bristol-Myers Squibb-Pfizer Alliance; HI-PRO ClinicalTrials.gov number, NCT04168203.).