Two doses of rivaroxaban versus aspirin for prevention of recurrent venous thromboembolism

Summary

Patients with unprovoked venous thromboembolism (VTE) are at high risk for recurrence. Although rivaroxaban is effective for extended VTE treatment at a dose of 20 mg once daily, use of the 10 mg dose may further improve its benefit-to-risk ratio. Low-dose aspirin also reduces rates of recurrent VTE, but has not been compared with anticoagulant therapy. The EINSTEIN CHOICE study is a multicentre, randomised, double-blind, active-controlled, event-driven study comparing the efficacy and safety of two once daily doses of rivaroxaban (20 and 10 mg) with aspirin (100 mg daily) for the prevention of recurrent VTE in patients who completed 6–12 months of anticoagulant therapy for their index acute VTE event. All treatments will be given for 12 months. The primary efficacy objective is to determine whether both doses of rivaroxaban are superior to aspirin for the prevention of symptomatic recurrent VTE, while the principal safety outcome is the incidence of major bleeding. The trial is anticipated to enrol 2,850 patients from 230 sites in 31 countries over a period of 27 months. In conclusion, the EINSTEIN CHOICE study will provide new insights into the optimal antithrombotic strategy for extended VTE treatment by comparing two doses of rivaroxaban with aspirin (clinicaltrials.gov NCT02064439).

Keywords

Venous thrombosis - deep-vein thrombosis - pulmonary embolism - anti-platelet agents - prevention

• References

• 1 Kearon C, Akl EA, Comerota AJ. et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: e419S-494S.
• 2 Prandoni P, Noventa F, Ghirarduzzi A. et al. The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica 2007; 92: 199-205.
• 3 Tagalakis V, Patenaude V, Kahn SR. et al. Treatment patterns of venous thromboembolism in a real-world population: the Q-VTE study cohort. Thromb Res 2014; 134: 795-802.
• 4 Ageno W, Samperiz A, Caballero R. et al. Duration of anticoagulation after venous thromboembolism in real world clinical practice. Thromb Res 2015; 135: 666-672.
• 5 Brighton TA, Eikelboom JW, Mann K. et al. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med 2012; 367: 1979-1987.
• 6 Becattini C, Agnelli G, Schenone A. et al. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med 2012; 366: 1959-1967.
• 7 Simes J, Becattini C, Agnelli G. et al. Aspirin for the prevention of recurrent venous thromboembolism: the INSPIRE collaboration. Circulation 2014; 130: 1062-1071.
• 8 Yeh CH, Gross PL, Weitz JI. Evolving use of new oral anticoagulants for treatment of venous thromboembolism. Blood 2014; 124: 1020-1028.
• 9 Schulman S, Kearon C, Kakkar AK. et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med 2013; 368: 709-718.
• 10 EINSTEIN Investigators. Bauersachs R, Berkowitz SD. et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363: 2499-2510.
• 11 Agnelli G, Buller HR, Cohen A. et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med 2013; 368: 699-708.
• 12 EINSTEIN Investigators. Buller HR, Prins MH. et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012; 366: 1287-1297.
• 13 Prins MH, Lensing AW, Bauersachs R. et al. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies. Thromb J 2013; 11: 21.
• 14 Bamber L, Wang MY, Prins MH. et al. Patient-reported treatment satisfaction with oral rivaroxaban versus standard therapy in the treatment of acute symptomatic deep-vein thrombosis. Thromb Haemost 2013; 110: 732-741.
• 15 Prins MH, Bamber L, Cano SJ. et al. Patient-reported treatment satisfaction with oral rivaroxaban versus standard therapy in the treatment of pulmonary embolism; results from the EINSTEIN PE trial. Thromb Res 2015; 135: 281-288.
• 16 Eriksson BI, Kakkar AK, Turpie AG. et al. Oral rivaroxaban for the prevention of symptomatic venous thromboembolism after elective hip and knee replacement. J Bone Joint Surgery Brit Vol 2009; 91: 636-644.
• 17 Cohen AT, Spiro TE, Buller HR. et al. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med 2013; 368: 513-523.
• 18 Shih JH. Sample size calculation for complex clinical trials with survival endpoints. Controlled Clin Trials 1995; 16: 395-407.
• 19 Kearon C, Ginsberg JS, Kovacs MJ. et al, Extended Low-Intensity Anticoagulation for Thrombo-Embolism I. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med 2003; 349: 631-699.
• 20 Ridker PM, Goldhaber SZ, Danielson E. et al. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med 2003; 348: 1425-1434.