Anticoagulation to prevent ischemic stroke and neurocognitive impairment in atrial fibrillation: the BRAIN-AF randomized clinical trial

作者：Léna Rivard, P. G. Khairy, Mario Talajic, J.C. Tardif, Jeff S. Healey, Sandra E. Black, Jason Andrade, Thalia S. Field, Isabelle Nault, Louis Bherer, Fadi Massoud, Stanley Nattel, Sylvain Lanthier, Normand Racine, Jean-François Roux, Isabelle Greiss, L. Macle, Peter G. Guerra, Rafik Tadros, Hélène Mayrand, Gilbert Gosselin, David Conen, Christian Bocti, Céline Chayer, Yan Deschaintre, Roopinder K. Sandhu, Jaimie Manlucu, Yaariv Khaykin, Atul Verma, Blandine Mondésert, Katia Dyrda, JULIA CADRIN-TOURIGNY, B. Thibault, Alexandre Raymond-Paquin, Martín Aguilar, Judith Brouillette, André Roussin, Alain Robillard, M. Tremblay-Gravel, Louis‐Philippe David, Mariève Cossette, Ratika Parkash, Marie-Claude Guertin, Denis Roy, on behalf of the BRAIN-AF investigators, A. Shekhar Pandey, FRANCIS PICHETTE, Miguel Barrero, Teresa Kuś, Ariane Lemieux, Valérie Gaudreault, Peiman Marzban, Jorge Wong, PETER LEONG SIT, David Laflamme, Ronald A.F. Fowlis, Kenneth Quadros, Anmol Kapoor, Umjeet Jolly, Stephen B. Wilton, Fabian Alejandro Azzari, Paul Dorian, François Deslongchamps, Yves Pesant, Saul Vizel, TunZan Maung, Michael Heffernan, Pablo B. Nery, Greg Curnew, Stéphanie Bourgeois, Vidal Essebag, Simon Kouz, Luc Cormier, John Vyselaar, R Chehayeb, Clarence Khoo, Anil Gupta, Ricardo Bessoudo, RAKESH BHARGAVA, F. Sandrin, Gernot Schram, François St-Maurice, Winston Tsui, William Liang · 发表于：Nature Medicine · 年份：2026 · DOI：10.1038/s41591-025-04101-y · 被引用次数：5 · 研究领域：Atrial Fibrillation Management and Outcomes、Acute Ischemic Stroke Management、Cardiovascular Disease and Adiposity

Individuals with atrial fibrillation (AF) are at increased risk of stroke, cognitive impairment and dementia. Observational studies suggest that anticoagulation may reduce the risk of cognitive decline in patients with AF and elevated thromboembolic risk, implicating subclinical cerebral emboli as a potential mechanistic link. Whether anticoagulation prevents cognitive deterioration in patients with AF at low risk of stroke remains uncertain. Here we conducted a multicenter, double-blind, placebo-controlled trial in which participants with AF and low thromboembolic risk (CHA2DS2-VASc scores of 0 or 1, excluding female sex) were randomized 1:1 to receive rivaroxaban 15 mg daily or placebo. The primary outcome was a composite of cognitive decline (≥2-point drop in Montreal Cognitive Assessment), stroke or transient ischemic attack with a motor deficit or aphasia. The trial was halted after meeting the predetermined futility criterion following a planned interim analysis, with 1,235 of the intended 1,424 participants (919 men; 316 women) enrolled. Over a median follow-up of 3.7 years, the primary outcome occurred in 256 (20.7%) participants, at an annual rate of 7.0% with rivaroxaban versus 6.4% with placebo, yielding a hazard ratio of 1.10 (95% confidence interval (0.86–1.40); P = 0.46). Conditional power analysis indicated a 1.2% probability of achieving a statistically significant treatment effect if the trial had been continued to its planned total of 410 events. Major bleed...