More Than an Aspirin a Day to Keep Recurrent Venous Thromboembolism Away

Whether to extend anticoagulant therapy for a deep vein thrombosis or pulmonary embolism beyond the acute treatment period can be a problematic decision. Anticoagulant therapy reduces the risk of recurrent venous thromboembolic events (VTE), but at the cost of an increased risk of bleeding. Reducing the intensity of anticoagulant therapy^1-3  or switching to aspirin³  have both been proposed as options in patients who wish to continue protection, but the efficacy and safety of these strategies is still uncertain.

Dr. Jeffrey I. Weitz and colleagues reported the results of a double-blind, randomized controlled trial, “EINSTEIN CHOICE,” which compared rivaroxaban 10 mg daily (low intensity) with rivaroxaban 20 mg daily (standard intensity) and aspirin 100 mg daily for prevention of recurrent VTE. All 3,365 randomly assigned patients received six to 12 months of anticoagulant therapy prior to enrollment. Patients with provoked or unprovoked VTE were eligible as long as their clinician believed there was uncertainty about the value of long-term treatment. Study duration was up to 12 months. The primary efficacy outcome measure was symptomatic fatal or nonfatal recurrent VTE, and the primary safety outcome was major bleeding.

The results showed that the rivaroxaban 20-mg and 10-mg doses were both superior to aspirin for the prevention of recurrent VTE (rivaroxaban 20 mg, 1.5%; rivaroxaban 10 mg, 1.2%; aspirin, 4.4%; HR [rivaroxaban 20 mg vs. aspirin], 0.34; 95% CI, 0.20-0.59; p<0.001; HR [rivaroxaban 10 mg vs. aspirin], 0.26; 95% CI, 0.14-0.47; p<0.001). Between the two doses of rivaroxaban, there was no difference in the risk of recurrence (HR, 1.34; 95% CI, 0.65-2.75; p=0.42) or the risk of major bleeding (0.5% and 0.4%, respectively). Furthermore, the risk of major bleeding in both rivaroxaban arms was similar to aspirin (0.3%). The risk of clinically relevant nonmajor bleeding was not significantly different across the three groups (rivaroxaban 10 mg, 2.0%; rivaroxaban 20 mg, 2.7%; aspirin, 1.8%).

There are important limitations to this study that should be considered. First, the total number of events (80) was small. This is likely due to the substantial proportion of patients with provoked VTE enrolled in the study (60%). This group is known to have a low risk of recurrence without anticoagulant therapy; therefore their inclusion in the study is controversial.⁵  Additionally, the duration of treatment was limited to one year. Patients facing this choice are deciding if they should continue anticoagulation indefinitely, which can mean decades of treatment. Lastly, the study was not powered to determine if 10 mg of rivaroxaban is noninferior to 20 mg with respect to efficacy.