Rivaroxaban in Rheumatic Heart Disease–Associated Atrial Fibrillation

Stuart J. Connolly, Ganesan Karthikeyan, Mpiko Nt, Abraham Haileamlak, Ahmed El Sayed, Alaa El Ghamrawy, Albertino Damasceno, Alvaro Avezum, Antonio M.L. Dans, Bernard Gitura, Dayi Hu, Emmanuel R. Kamanzi, Fathi Maklady, Golden Fana, J. Antonio Gonzalez-Hermosillo, John Musuku, Khawar Kazmi, Liesl Zühlke, Lillian Gondwe, Changsheng MaMaria Paniagua, Okechukwu S. Ogah, Onkabetse J. Molefe-Baikai, Peter Lwabi, Pilly Chillo, Sanjib K. Sharma, Tantchou T.J. Cabral, Wadea M. Tarhuni, Alexander Benz, Martin van Eikels, Amy Krol, Divya Pattath, Kumar Balasubramanian, Sumathy Rangarajan, Chinthanie Ramasundarahettige, Bongani Mayosi, Salim Yusuf

Research output: Contribution to journalArticlepeer-review

100 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)978-988
Number of pages11
JournalNew England Journal of Medicine
Issue number11
Publication statusPublished - 15 Sept 2022
Externally publishedYes


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