Rivaroxaban in Rheumatic Heart Disease-Associated Atrial Fibrillation

N Engl J Med. 2022 Sep 15;387(11):978-988. doi: 10.1056/NEJMoa2209051. Epub 2022 Aug 28.

Abstract

Background: Testing of factor Xa inhibitors for the prevention of cardiovascular events in patients with rheumatic heart disease-associated atrial fibrillation has been limited.

Methods: We enrolled patients with atrial fibrillation and echocardiographically documented rheumatic heart disease who had any of the following: a CHA2DS2VASc score of at least 2 (on a scale from 0 to 9, with higher scores indicating a higher risk of stroke), a mitral-valve area of no more than 2 cm2, left atrial spontaneous echo contrast, or left atrial thrombus. Patients were randomly assigned to receive standard doses of rivaroxaban or dose-adjusted vitamin K antagonist. The primary efficacy outcome was a composite of stroke, systemic embolism, myocardial infarction, or death from vascular (cardiac or noncardiac) or unknown causes. We hypothesized that rivaroxaban therapy would be noninferior to vitamin K antagonist therapy. The primary safety outcome was major bleeding according to the International Society of Thrombosis and Hemostasis.

Results: Of 4565 enrolled patients, 4531 were included in the final analysis. The mean age of the patients was 50.5 years, and 72.3% were women. Permanent discontinuation of trial medication was more common with rivaroxaban than with vitamin K antagonist therapy at all visits. In the intention-to-treat analysis, 560 patients in the rivaroxaban group and 446 in the vitamin K antagonist group had a primary-outcome event. Survival curves were nonproportional. The restricted mean survival time was 1599 days in the rivaroxaban group and 1675 days in the vitamin K antagonist group (difference, -76 days; 95% confidence interval [CI], -121 to -31; P<0.001). A higher incidence of death occurred in the rivaroxaban group than in the vitamin K antagonist group (restricted mean survival time, 1608 days vs. 1680 days; difference, -72 days; 95% CI, -117 to -28). No significant between-group difference in the rate of major bleeding was noted.

Conclusions: Among patients with rheumatic heart disease-associated atrial fibrillation, vitamin K antagonist therapy led to a lower rate of a composite of cardiovascular events or death than rivaroxaban therapy, without a higher rate of bleeding. (Funded by Bayer; INVICTUS ClinicalTrials.gov number, NCT02832544.).

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Anticoagulants* / adverse effects
  • Anticoagulants* / therapeutic use
  • Atrial Fibrillation* / drug therapy
  • Atrial Fibrillation* / etiology
  • Echocardiography
  • Factor Xa Inhibitors* / adverse effects
  • Factor Xa Inhibitors* / therapeutic use
  • Female
  • Hemorrhage / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Rheumatic Heart Disease* / complications
  • Rheumatic Heart Disease* / diagnosis
  • Rheumatic Heart Disease* / diagnostic imaging
  • Rivaroxaban* / adverse effects
  • Rivaroxaban* / therapeutic use
  • Stroke / etiology
  • Stroke / prevention & control
  • Treatment Outcome
  • Vitamin K / antagonists & inhibitors
  • Warfarin / adverse effects
  • Warfarin / therapeutic use

Substances

  • Anticoagulants
  • Factor Xa Inhibitors
  • Vitamin K
  • Warfarin
  • Rivaroxaban

Associated data

  • ClinicalTrials.gov/NCT02832544