Direct oral anticoagulants for extended treatment of venous thromboembolism: insights from the EINSTEIN CHOICE study

Abstract

The risk of recurrence of venous thromboembolism (VTE) persists after interruption of the initial anticoagulation therapy. New evidence shows that direct oral anticoagulants are effective for extended treatment of VTE and may reduce the risk of all-cause mortality. The optimal duration of anticoagulation after VTE is, however, controversial and complicated by the need for individualised assessment and balance between thrombosis and bleeding risks. Three direct oral anticoagulants (rivaroxaban, apixaban and dabigatran) have been studied for extended treatment of VTE. Dabigatran was shown to be safer than vitamin K antagonists and similarly effective for the prevention of recurrent VTE. Dabigatran, apixaban and rivaroxaban resulted in significant decreases in the rate of recurrent symptomatic VTE when compared to placebo, without a statistically significant difference in the risk of major bleeding. The latest guidelines of the American College of Chest Physicians suggest the use of low-dose aspirin to prevent VTE recurrence in patients who want to stop anticoagulation. In the randomised, double-blind, phase 3 EINSTEIN CHOICE trial, once-daily rivaroxaban at doses of 20 mg or 10 mg and 100 mg of aspirin were compared in VTE patients for whom there was clinical equipoise for extended anticoagulation. Either a treatment dose (20 mg) or a prophylactic dose (10 mg) of rivaroxaban significantly reduced the risk of VTE recurrence without a significant increase in bleeding risk compared with aspirin. The EINSTEIN CHOICE trial included patients with provoked or unprovoked VTE. Patients with VTE provoked by minor persistent or minor transient risk factors enrolled in this trial had not-negligible VTE recurrence rates. These new findings on extended therapy suggest the possibility of anticoagulation regimens at intensities tailored to the patients' risk profiles and VTE characteristics, with a shift of the risk-benefit balance in favour of extended treatment.

Figure 1

Venous thromboembolism recurrence and major bleeding rates in extension studies with direct oral anticoagulants. VTE: venous thromboembolism; ASA: aspirin.

Figure 2

Primary efficacy endpoint (recurrent venous thromboembolism) in the EINSTEIN CHOICE trial. Kaplan-Meier curves. Adapted with permission from Weitz JI et al. VTE: venous thromboembolism.

Figure 3

Primary safety endpoint (major bleeding) in the EINSTEIN CHOICE trial. Kaplan-Meier curves. Adapted with permission from Weitz JI et al.