Dual Antiplatelet Therapy and Immediate Intensive Statin in Mild Ischemic Stroke: A Randomized Trial

Previous studies have shown a beneficial effect of clopidogrel-aspirin and intensive statin therapy in acute ischemic stroke; however, the synergistic effect of the 2 treatments is still unclear. The aim of this study was to investigate the effect of combining clopidogrel-aspirin and immediate intensive statin in patients with acute mild ischemic stroke or transient ischemic attack (TIA).

We performed a multicenter, randomized, double-blind, placebo-controlled trial with a 2-by-2 factorial design across 222 hospitals in China. Eligible participants were patients with acute mild ischemic stroke or TIA of a presumed atherosclerotic cause within 72 hours of symptom onset. Patients were randomly assigned to receive clopidogrel plus aspirin or aspirin alone and an immediate or delayed intensive statin. The primary efficacy outcome was a new stroke (ischemic or hemorrhagic) within 90 days, and the primary safety outcome was moderate-to-severe bleeding.

Between September 17, 2018, and October 15, 2022, 6,100 patients were enrolled (median age, 65 years; 64.2% male), of whom 1,525 each were assigned to the 4 groups. New stroke within 90 days occurred in 116 patients (7.6%) in the clopidogrel-aspirin plus immediate intensive statin group (hazard ratio [HR] 0.76, 95% CI 0.60-0.97), in 106 patients (7.0%) in the clopidogrel-aspirin plus delayed statin group (HR 0.69, 95% Cl 0.54-0.89), and in 129 patients (8.5%) in the aspirin plus immediate statin group (HR 0.85, 95% Cl 0.67 to 1.07), compared with 150 patients (9.9%) in the aspirin plus delayed intensive statin group. Moderate-to-severe bleeding occurred in 17 (1.1%) in the clopidogrel-aspirin plus immediate statin group (p = 0.047), 10 (0.7%) in the clopidogrel-aspirin plus delayed statin group (p = 0.46), and 6 (0.4%) in the aspirin plus immediate statin group (p = 0.80), compared with 7 (0.5%) in the aspirin plus delayed statin group.

Among patients with mild ischemic stroke or TIA of presumed atherosclerotic cause, the combination of clopidogrel-aspirin and delayed intensive statin was superior to aspirin plus delayed intensive statin in reducing the risk of new stroke, an effect that was mainly driven by clopidogrel-aspirin and not significantly different from that of clopidogrel-aspirin plus immediate statin. The combination treatment had a low but increased risk of moderate-to-severe bleeding.

ClinicalTrials.gov identifier: NCT03635749.

This study provides Class I evidence that in patients with mild ischemic stroke or TIA of presumed atherosclerotic cause, the combination of clopidogrel-aspirin plus delayed intensive statin was superior to aspirin plus delayed intensive statin in reducing the 90-day risk of new stroke.