Factor Xa inhibitor more effective than aspirin for long-term prevention of recurrent VTE
Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism
Presented at ACC.17 by Philip S. Wells
In patients without reversible risk factors, the risk of recurrent venous thromboembolism (VTE) is up to 10% in the first year if anticoagulation therapy is stopped. Guidelines recommend the use of direct oral anticoagulant agents, such as rivaroxaban, for at least 3 months, for the prevention of VTE in high risk patients. However, in clinical practice, concerns about bleeding often lead to reluctance to continue anticoagulant therapy beyond 6 to 12 months.
Lower dose anticoagulant therapy, or aspirin instead of an anticoagulant may reduce this bleeding risk. Head-to-head comparison is necessary to determine the relative efficacy and safety of these approaches.
In this study, the efficacy and safety of two doses of rivaroxaban (10 mg or 20 mg once daily) and of aspirin, were assessed in 3365 patients with VTE, who had completed 6 to 12 months of anticoagulation therapy and for whom there was uncertainty regarding the need for continued anticoagulation. Primary efficacy outcome was symptomatic recurrent VTE (Non-fatal DVT or PE, fatal PE, or unexplained death where PE cannot be excluded).
- A primary efficacy outcome event occurred in 1.5% of patients who were receiving 20 mg of rivaroxaban and in 1.2% of patients receiving 10 mg, as compared with 4.4% of patients who were receiving aspirin.
- Fatal VTE occurred in 0.2% of patients in the 20 mg rivaroxaban group, in no patients in the 10 mg rivaroxaban group, and in 0.2% of patients in the aspirin group.
- Both rivaroxaban doses were superior to aspirin with respect to the primary efficacy outcome (HR for 20 mg rivaroxaban vs. aspirin: 0.34; 95% CI: 0.20 - 0.59; HR for 10 mg rivaroxaban vs. aspirin: 0.26; 95% CI: 0.14 - 0.47; P<0.001 for both comparisons).
- The HR for the comparison between the 20-mg and 10-mg rivaroxaban regimens was 1.34 (95% CI: 0.65 - 2.75; P = 0.42).
- Rates of recurrence in patients whose index events were provoked or unprovoked were lower in both the 20-mg rivaroxaban group (1.4% and 1.8%, respectively) and the 10-mg rivaroxaban group (0.9% and 1.5%, respectively) compared with the aspirin group.
- Major bleeding occurred in 0.5% of patients in the 20-mg rivaroxaban group and in 0.4% of patients in the 10-mg rivaroxaban group, as compared with 0.3% in the aspirin group.
- MI, stroke, or systemic embolism occurred in 0.3% in the 20-mg rivaroxaban group, in 0.4% in the 10-mg rivaroxaban group, and in 0.6% of patients in the aspirin group.
- The rates of death from any cause were 0.7% and 0.2% in the 20-mg and 10-mg rivaroxaban groups, respectively, as compared with 0.6% in the aspirin group.
Rivaroxaban, at both a treatment dose (20 mg) and a thrombo-prophylactic dose (10 mg), was more effective than aspirin for the prevention of recurrent VTE in patients for whom there was uncertainty about the benefit of continued anticoagulation. Rates of bleeding were similar between all treatment groups.
During the press conference, dr. Wells concluded that these data show that there is no role for aspirin in the extended phase of prevention of recurrent VTE.
In their editorial article, Crowther and Cuker provide an interpretation of the findings of the Weitz et al study, by considering them as qualitative evidence supporting the long-term use of low dose rivaroxaban, in particular for patients with provoked venous thromboembolism at median risk for bleeding and high risk for a recurrent thromboembolic event.
The authors conclude: ‘The emergence of rivaroxaban and other direct oral anticoagulant agents has altered the standard of care among patients with venous thromboembolism. For patients without cancer, the use of direct oral anticoagulant agents might be considered as first-line treatment for those with acute venous thromboembolism. Full-dose treatment could be continued for a minimum of 3 to 6 months. In patients in whom there is equipoise with respect to continuing anticoagulant therapy beyond this period, the use of a reduced-intensity direct oral anticoagulant agent might be considered. Clinicians who choose this strategy can be confident of excellent efficacy and low bleeding risk similar to that observed with aspirin or placebo.’