Reduced-Dosed Rivaroxaban in the Long-Term Prevention of Recurrent Symptomatic Venous Thromboembolism - EINSTEIN CHOICE

Mar 18, 2017
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Bayer Pharmaceuticals
Date Presented:
03/18/2017
Date Published:
03/18/2017
Original Posted Date:
03/18/2017
References

Contribution To Literature:

Among patients in the EINSTEIN CHOICE trial who had completed a 6- to 12-month course of anticoagulation for VTE, extending anticoagulation with either prophylaxis (10 mg) or treatment (20 mg) doses of rivaroxaban for 1 year is superior to aspirin in reducing recurrent VTE events.

Description:

The goal of the trial was to assess the safety and efficacy of rivaroxaban 20 mg and rivaroxaban 10 mg daily compared with placebo in patients with symptomatic venous thromboembolism (VTE) who had completed a 6- to 12-month course of anticoagulation.

Study Design

Patients were randomly assigned in a 1:1:1 ratio to either rivaroxaban 20 mg once daily (n = 1,107), rivaroxaban 10 mg once daily (n = 1,127), or aspirin 100 mg (n = 1,131). Treatment was continued for at least another 6 months, but typically up to 1 additional year.

  • Total number of enrollees: 3,365
  • Duration of follow-up: 1 year
  • Mean patient age: 58 years
  • Percentage female: 45%

Inclusion criteria:

  • ≥18 years of age
  • Objectively confirmed, symptomatic proximal deep-vein thrombosis or pulmonary embolism
  • Treated for 6-12 months with an anticoagulant agent, including a vitamin K antagonist or a direct oral anticoagulant agent, and had not interrupted therapy for >7 days before randomization

Exclusion criteria:

  • Contraindication to continuation of anticoagulation
  • Required extended anticoagulant therapy at therapeutic doses or antiplatelet therapy
  • Calculated creatinine clearance of <30 ml/min or hepatic disease associated with a coagulopathy

Other salient features/characteristics:

  • Index VTE classified as unprovoked: 40%
  • Known thrombophilia: 7%; prior VTE: 17%
  • Active cancer: 3%

Principal Findings:

The primary endpoint, composite of symptomatic, recurrent fatal or nonfatal VTE and unexplained death for rivaroxaban 20 mg vs. rivaroxaban 10 mg vs. aspirin, was 1.5% vs. 1.2% vs. 4.4% (hazard ratio [HR] for rivaroxaban 20 mg vs. aspirin: 0.34, 95% confidence interval [CI] 0.20-0.59; HR for rivaroxaban 10 mg vs. aspirin: 0.26, 95% CI 0.14-0.47).

  • Recurrent VTE: 0.8% vs. 0.6% vs. 2.6%
  • Fatal VTE: 0.2% vs. 0% vs. 0.2%

Secondary outcomes for rivaroxaban 20 mg vs. rivaroxaban 10 mg vs. aspirin:

  • MI: 0.1% vs. 0% vs. 0.4%
  • Ischemic stroke: 0.2% vs. 0.4% vs. 0.2%
  • All-cause mortality: 0.7% vs. 0.2% vs. 0.6%
  • Major bleeding: 0.5% vs. 0.4% vs. 0.3%, p = 0.32
  • Clinically relevant nonmajor bleeding: 2.7% vs. 2.0% vs. 1.8%, p for rivaroxaban 20 mg vs. aspirin = 0.14

Interpretation:

The results of this important trial indicate that among patients who had completed a 6- to 12-month course of anticoagulation for both provoked or unprovoked VTE, extending anticoagulation with either prophylaxis (10 mg) or treatment (20 mg) doses of rivaroxaban for 1 year is superior to aspirin in reducing recurrent VTE events. The bleeding risk was numerically higher with rivaroxaban 20 mg daily, but not statistically significant.  The findings of this trial are likely to influence clinical practice. Similar results have been reported for apixaban earlier in the AMPLIFY-EXT trial.

The results of this trial are not generalizable to patients who have a clear indication for long-term anticoagulation therapy and who were thus ineligible to participate in the trial. Given a tenacious long-term risk of VTE in patients with an index event, it is unclear if even longer-term treatment with rivaroxaban or other direct oral anticoagulants would be beneficial.

References:

Weitz JI, Lensing AW, Prins MH, et al., on behalf of the EINSTEIN CHOICE Investigators. Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism. N Engl J Med 2017;Mar 18:[Epub ahead of print].

Presented by Dr. Phil Wells at the American College of Cardiology Annual Scientific Session (ACC 2017), Washington, DC, March 18, 2017.

Keywords: ACC17, ACC Annual Scientific Session, Anticoagulants, Aspirin, Double-Blind Method, Embolism, Hemorrhage, Myocardial Infarction, Neoplasms, Pulmonary Embolism, Random Allocation, Risk Factors, Stroke, Venous Thromboembolism, Venous Thrombosis, Vascular Diseases, Vitamin K


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