What is the safest and most effective therapy for the extended treatment of venous thromboembolism?

As compared with aspirin, the use of rivaroxaban to extend anticoagulation beyond the initial 6 to 12 months to treat provoked or unprovoked venous thromboembolism (VTE) reduces the risk of recurrent symptomatic VTE without increasing the risk of bleeding. You would need to treat approximately 30 to 33 patients with either full-dose or low-dose rivaroxaban to prevent 1 additional clot. (LOE = 1b)

Weitz JI, Lensing AWA, Prins MH, et al, for the EINSTEIN CHOICE Investigators. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med 2017;376(13):1211-1222.  [PMID:28316279]

Randomized controlled trial (double-blinded)

Industry

Concealed

Outpatient (any)

These authors recruited 3396 adult patients with symptomatic proximal deep venous thrombosis or pulmonary embolism who had received 6 to 12 months of anticoagulation with a vitamin K antagonist or a direct oral anticoagulant. Those who already required extended anticoagulation therapy were excluded. Patients were then randomized, using concealed allocation, to receive either rivaroxaban 20 mg, rivaroxaban 10 mg, or aspirin 100 mg once daily along with a placebo version of the treatment they were not receiving. The 3 groups had similar baseline characteristics: approximately 60% of the index VTEs were provoked and 40% were unprovoked. The median duration of study treatment was also similar across the 3 groups at almost 12 months. After excluding patients who did not take any study medications, 3365 patients were included in the intention-to-treat analysis. The primary outcome—a composite of symptomatic, recurrent, fatal or nonfatal VTE—was decreased in both rivaroxaban groups as compared with the aspirin group (rivaroxaban 20 mg vs aspirin: 1.5% vs 4.4%, hazard ratio [HR] 0.34; 95% CI 0.20 - 0.59; rivaroxaban 10 mg vs aspirin: 1.2% vs 4.4%; HR 0.26; 0.14 - 0.47). Rates of major bleeding and clinically relevant nonmajor bleeding were similar in all 3 groups (major bleeding: 0.5% with 20 mg, 0.4% with 10 mg, 0.3% with aspirin; nonmajor bleeding: 2.7% with 20 mg, 2.0% with 10 mg, 1.8% with aspirin). This study was not powered to determine whether the lower dose of rivaroxaban is noninferior to the higher dose.