A Controlled Trial of Rivaroxaban after Transcatheter Aortic-Valve Replacement

N Engl J Med. 2020 Jan 9;382(2):120-129. doi: 10.1056/NEJMoa1911425. Epub 2019 Nov 16.

Abstract

Background: Whether the direct factor Xa inhibitor rivaroxaban can prevent thromboembolic events after transcatheter aortic-valve replacement (TAVR) is unclear.

Methods: We randomly assigned 1644 patients without an established indication for oral anticoagulation after successful TAVR to receive rivaroxaban at a dose of 10 mg daily (with aspirin at a dose of 75 to 100 mg daily for the first 3 months) (rivaroxaban group) or aspirin at a dose of 75 to 100 mg daily (with clopidogrel at a dose of 75 mg daily for the first 3 months) (antiplatelet group). The primary efficacy outcome was the composite of death or thromboembolic events. The primary safety outcome was major, disabling, or life-threatening bleeding. The trial was terminated prematurely by the data and safety monitoring board because of safety concerns.

Results: After a median of 17 months, death or a first thromboembolic event (intention-to-treat analysis) had occurred in 105 patients in the rivaroxaban group and in 78 patients in the antiplatelet group (incidence rates, 9.8 and 7.2 per 100 person-years, respectively; hazard ratio with rivaroxaban, 1.35; 95% confidence interval [CI], 1.01 to 1.81; P = 0.04). Major, disabling, or life-threatening bleeding (intention-to-treat analysis) had occurred in 46 and 31 patients, respectively (4.3 and 2.8 per 100 person-years; hazard ratio, 1.50; 95% CI, 0.95 to 2.37; P = 0.08). A total of 64 deaths occurred in the rivaroxaban group and 38 in the antiplatelet group (5.8 and 3.4 per 100 person-years, respectively; hazard ratio, 1.69; 95% CI, 1.13 to 2.53).

Conclusions: In patients without an established indication for oral anticoagulation after successful TAVR, a treatment strategy including rivaroxaban at a dose of 10 mg daily was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than an antiplatelet-based strategy. (Funded by Bayer and Janssen Pharmaceuticals; GALILEO ClinicalTrials.gov number, NCT02556203.).

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aspirin / adverse effects
  • Aspirin / therapeutic use*
  • Atrial Fibrillation / drug therapy
  • Cardiovascular Diseases / mortality
  • Clopidogrel / adverse effects
  • Clopidogrel / therapeutic use*
  • Drug Therapy, Combination
  • Factor Xa Inhibitors / adverse effects
  • Factor Xa Inhibitors / therapeutic use*
  • Female
  • Heart Valve Prosthesis
  • Hemorrhage / chemically induced
  • Humans
  • Intention to Treat Analysis
  • Kaplan-Meier Estimate
  • Male
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Rivaroxaban / adverse effects
  • Rivaroxaban / therapeutic use*
  • Thromboembolism / mortality
  • Transcatheter Aortic Valve Replacement*

Substances

  • Factor Xa Inhibitors
  • Platelet Aggregation Inhibitors
  • Rivaroxaban
  • Clopidogrel
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT02556203