Abstract
BACKGROUND: Branch atherosclerosis disease (BAD) is prone to early neurological deterioration (END). The purpose of this study was to assess the efficacy and safety of argatroban plus dual antiplatelet therapy (DAPT) for preventing END in high-risk branch atherosclerosis disease patients. METHODS: This multicenter, open-label, blinded end point, randomized controlled trial including branch atherosclerosis disease patients with mild stroke (National Institutes of Health Stroke Scale score ≤5) was conducted at 4 centers in China from May 18, 2021 to February 8, 2023. Within 48 hours after symptom onset, patients were randomly assigned to receive argatroban plus DAPT or DAPT alone in a 1:1 ratio. The primary end points were the incidence of END (National Institutes of Health Stroke Scale score increase ≥2) within 7 days and excellent functional outcome (modified Rankin Scale score of 0 to 1) at 90 days. RESULTS: A total of 111 patients were randomized, with 11 excluded for specific reasons, resulting in 100 patients included in the modified intention-to-treat population. Among the 100 patients, 49 received argatroban plus DAPT and 51 received DAPT alone, 63 (63.0%) were men, and the median age was 64 (range, 55-74) years. END occurred in 20.4% (10/49) of the argatroban plus DAPT group and 47.1% (24/51) of the DAPT group (risk difference, 26.7% [95% CI, 14.1-39.2]; risk ratio, 2.31 [95% CI, 1.49-3.58]; P=0.006). At the 90-day follow-up, 87.8% (43/49) in the argatroban plus DAPT group and 68.6% (35/51) in the DAPT group achieved an excellent functional outcome (risk difference, -19.1% [95% CI, -30.3 to -8.0]; risk ratio, 0.78 [95% CI, 0.67-0.91]; P=0.025). There was 1 minor hemorrhage in each group. CONCLUSIONS: Argatroban plus DAPT is a safe and effective strategy to reduce END occurrence and improve 90-day functional outcome in high-risk branch atherosclerosis disease patients. REGISTRATION: URL: https://www.chictr.org.cn; Unique Identifier: ChiCTR21000 46487.