BRAIN-AF

(2026)

Objective

To determine whether low-dose rivaroxaban (15 mg once daily) reduces a composite of cognitive decline, stroke, or transient ischemic attack (TIA) compared with placebo in patients with AF at low thromboembolic risk (CHA₂DS₂-VASc 0–1 excluding female sex) and no established indication for anticoagulation.

Study Summary

• Low-dose rivaroxaban did not reduce the composite of cognitive decline, stroke, or TIA in low-risk AF patients (HR 1.10, 95% CI 0.86–1.40; P=0.46).
• The trial was stopped early for futility after a median 3.7 years; cognitive decline accounted for >91% of primary outcome events, and major bleeding was rare in both arms.

Intervention

Rivaroxaban 15 mg daily vs matching placebo

Inclusion Criteria

Age 30–62 years; non-valvular AF (paroxysmal, persistent, or permanent) documented within the prior 2 years; low stroke risk per CCS-AF guidelines (no prior stroke/TIA, no hypertension, no diabetes, no congestive heart failure); no other indication for oral anticoagulation; MMSE ≥25; no known dementia.

Study Design

Arms: Array

Patients per Arm: 611 rivaroxaban, 624 placebo (ITT; 1,235 randomized after 3 exclusions)

Outcome

Primary composite (≥2-point drop in MoCA, stroke, or TIA with motor deficit/aphasia): 130/610 (21.3%) rivaroxaban vs 126/623 (20.2%) placebo — HR 1.10, 95% CI 0.86–1.40, P=0.46 (annualized 7.0% vs 6.4%); trial stopped early for futility (conditional power 1.2%). Stroke/TIA/systemic embolism: 15/611 (2.5%) vs 17/624 (2.7%) (HR 0.92, 95% CI 0.50–1.84). Major bleeding: 2 (0.09%/yr) vs 5 (0.21%/yr), P=0.27. No fatal bleeding.

Trial not found