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.