Clinical Question

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

Bottom Line

Compared with aspirin, the use of rivaroxaban (Xarelto) to extend anticoagulation beyond the initial six to 12 months to treat provoked or unprovoked 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 full- or low-dose rivaroxaban to prevent one additional clot. (Level of Evidence = 1b)

Synopsis

These authors recruited 3,396 adult patients with symptomatic proximal deep venous thrombosis or pulmonary embolism who had received six 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 20 mg of rivaroxaban, 10 mg of rivaroxaban, or 100 mg of aspirin once daily with a placebo version of the treatment they were not receiving. The three 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 three groups at almost 12 months.

After excluding patients who did not take any study medications, 3,365 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 compared with the aspirin group (20-mg rivaroxaban vs. aspirin: 1.5% vs. 4.4%; hazard ratio [HR] = 0.34; 95% confidence interval [CI], 0.20 to 0.59; 10-mg rivaroxa-ban vs. aspirin: 1.2% vs. 4.4%; HR = 0.26; 95% CI, 0.14 to 0.47). Rates of major bleeding and clinically relevant nonmajor bleeding were similar in all three groups (major bleeding: 0.5% with 20-mg rivaroxaban vs. 0.4% with 10-mg rivaroxaban vs. 0.3% with aspirin; non-major bleeding: 2.7% with 20 mg vs. 2.0% with 10 mg vs. 1.8% with aspirin). This study was not powered to determine whether the lower dose of rivaroxaban is noninferior to the higher dose.

Study design: Randomized controlled trial (double-blinded)

Funding source: Industry

Allocation: Concealed

Setting: Outpatient (any)

Reference:WeitzJILensingAWPrinsMHet alEINSTEIN CHOICE InvestigatorsRivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med2017;376(13):1211–1222.