Rivaroxaban in Rheumatic Heart Disease–Associated Atrial Fibrillation
Stuart J. Connolly, Ganesan Karthikeyan, Mpiko Ntsekhe, Abraham Haileamlak, Ahmed El Sayed, Alaa El Ghamrawy, Albertino Damasceno, Álvaro Avezum, Antonio M.L. Dans, Bernard Gitura, Dayi Hu, Emmanuel Kamanzi, Fathi Maklady, Golden Fana, Jesús Antonio González-Hermosillo, John Musuku, Khawar Kazmi, Liesl Zühlke, Lillian Gondwe, Changsheng Ma, María Paniagua, Okechukwu S. Ogah, Onkabetse Julia Molefe‐Baikai, Peter Lwabi, Pilly Chillo, Sanjib K. Sharma, Tantchou Tchoumi Jacques Cabral, Wadea Tarhuni, Alexander P. Benz, Martin van Eikels, Amy Krol, Divya Pattath, Kumar Balasubramanian, Sumathy Rangarajan, Chinthanie Ramasundarahettige, Bongani M. Mayosi, Salim Yusuf
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: , 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.).