Clopidogrel plus Aspirin Has Benefits for TIA or Minor Stroke

In 2013, the CHANCE study showed that in patients with transient ischemic attack (TIA) or minor stroke, short-term (21-day) dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel (A+C) was associated with a 32% reduction in stroke and no increased bleeding risk compared with antiplatelet monotherapy (NEJM JW Neurol Aug 2013 and N Engl J Med 2013; 369:11). Whether these findings in China, with a high preponderance of intracranial atherosclerosis, apply to other populations was unclear.

To find out, researchers compared A+C versus aspirin alone in 4881 patients (mean age, 65; 45% women; 57% with stroke) from 269 international sites (83% in the U.S.). Most patients (58%) were already taking aspirin at study entry. Patients in the A+C group received a 600 mg loading dose of clopidogrel, followed by 75 mg daily for 90 days. The aspirin dose ranged from 50 to 325 mg per day. All patients had a high-risk transient ischemic attack (TIA; ABCD² score ≥4) or minor stroke (NIH stroke scale score ≤3) and were randomized within 12 hours after symptom onset. The primary endpoint was stroke, myocardial infarction, or vascular death within 90 days.

The primary endpoint occurred in 5.0% of patients taking A+C and 6.5% of patients taking aspirin alone, a significant difference (hazard ratio, 0.75; 95% confidence interval, 0.59–0.95). Stroke alone was 28% lower with A+C. Major (but not cerebral) hemorrhages were a significant 0.5% more common with A+C than aspirin alone (0.9% vs. 0.4%). In a secondary analysis, the benefit of A+C was greater at 7 days and 30 days than at 90 days.