Summary
background
Trials of factor Xa inhibitors for the prevention of cardiovascular events in patients with atrial fibrillation associated with rheumatic heart disease have been limited.
methods
Patients with atrial fibrillation and echocardiographically documented rheumatic heart disease who had any of the following characteristics were enrolled: a CHA2DS2VASc score of at least 2 (on a scale of 0 to 9, with higher scores indicating greater 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 non-cardiac) 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 Haemostasis.
results
Of the 4565 patients enrolled, 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 non-proportional. The restricted median 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). There was a greater incidence of death in the rivaroxaban group than in the vitamin K antagonist group (restricted median survival time, 1608 days vs. 1680 days; difference, -72 days; 95% CI, - 117 to -28). No significant difference was observed between groups in the rate of major bleeding.
Conclusions
Among patients with atrial fibrillation associated with rheumatic heart disease, vitamin K antagonist therapy resulted in a lower rate of cardiovascular events or death than rivaroxaban therapy, without a higher rate of bleeding. (Funded by Bayer; ClinicalTrials.gov number INVICTUS, NCT02832544.)