Essence of this Article
Although the risk of recurrent venous thromboembolism (VTE) reduces after the first few months of treatment, a residual risk remains. For patients who have received anticoagulation treatment for up to 3 months after a first episode of symptomatic deep vein thrombosis, the cumulative risk of VTE recurrence is approximately 18% after 2 years, 25% after 5 years and 30% after 8 years.497 Despite this risk, physicians often terminate anticoagulation after 6–12 months because the risk of bleeding is believed to outweigh the risk of recurrent VTE. EINSTEIN CHOICE is currently evaluating the already established 20 mg once-daily dose of rivaroxaban, a reduced 10 mg once-daily dose of rivaroxaban and a 100 mg once-daily dose of acetylsalicylic acid for the long-term prevention of recurrent VTE. The findings may enable alignment of anticoagulant treatment with the benefit–risk profile of the individual patient.
Extended Secondary Prevention of Venous Thromboembolism
Despite the continued risk of recurrent venous thromboembolism (VTE), anticoagulation is often withdrawn after 6–12 months owing to concerns over the risk of bleeding. Patients often receive no further treatment, or are switched to acetylsalicylic acid (ASA). Although international normalized ratio-adjusted vitamin K antagonist therapy is highly effective for the long-term secondary prevention of recurrent VTE, the limitations associated with this treatment (i.e. the need for continuous international normalized ratio monitoring and dose adjustments, patient compliance issues and the risk of major bleeding) can be burdensome for both patients and physicians.498 Although treatment with ASA does not involve the limitations traditionally associated with vitamin K antagonists, studies to date have shown a lesser efficacy compared with anticoagulation in the prevention of recurrent VTE. The ASPIRE499 and WARFASA500 studies followed patients who had received initial anticoagulation therapy (for 6 weeks–24 months and 6–18 months, respectively) after a first episode of unprovoked VTE. Results showed non-significant and significant reductions in recurrent VTE compared with placebo, respectively, without increasing the risk of major bleeding (Table).
|Study||ASA 100 mg (n/N)||Placebo (n/N)||HR (95% CI)||p-value|
|Clinically relevant bleeding|
Table: Acetylsalicylic acid versus placebo studies for preventing recurrent venous thromboembolism
ASA, acetylsalicylic acid; CI, confidence interval; HR, hazard ratio; VTE, venous thromboembolism.
EINSTEIN CHOICE (clinicaltrials.gov; NCT02064439), a multicentre, randomized, double-blind, event-driven phase III study, is investigating the superiority of oral Factor Xa inhibitor rivaroxaban at standard and reduced doses versus ASA for the long-term prevention of symptomatic VTE in patients who have completed between 6 and 12 months of anticoagulant treatment for acute VTE (Figure 1). The study is expected to enrol 2850 patients and will examine the rates of fatal or non-fatal symptomatic recurrent VTE and major bleeding.
EINSTEIN CHOICE is the fourth phase III study in the EINSTEIN clinical trial programme and follows on from EINSTEIN EXT. In EINSTEIN EXT, extended-duration therapy with rivaroxaban 20 mg once daily for 6 or 12 months was superior to placebo for the prevention of recurrent VTE in patients who had previously completed 6–12 months of treatment for deep vein thrombosis or pulmonary embolism.501 In addition, a reduction from the previously studied rivaroxaban 20 mg once-daily regimen may maintain efficacy while further improving the safety profile. Consequently, the results of the EINSTEIN CHOICE study may provide physicians with additional therapeutic options to ensure an optimal benefit–risk balance for patients during their treatment.