INSPIRES (antiplatelet therapy)
Trial question
What is the role of dual antiplatelet treatment initiated within 72 hours after stroke onset?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
36.0% female
64.0% male
N = 6100
6100 patients (2185 female, 3915 male).
Inclusion criteria: patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy.
Key exclusion criteria: receipt of thrombolysis or endovascular therapy; receipt of an additional anticoagulant, defibrinogenation, or antiplatelet therapy except for clopidogrel and aspirin after the index event; presumed cardioembolic TIA or ischemic stroke.
Interventions
N=3050 clopidogrel-aspirin (clopidogrel at a loading dose of 300 mg on the first day, followed by 75 mg daily on days 2 to 90 plus aspirin at a dose of 100-300 mg on day 1, then 100 mg daily for days 2 to 21).
N=3050 aspirin (matching clopidogrel placebo for 90 days plus aspirin at a dose of 100-300 mg on day 1, then 100 mg daily for days 2 to 90).
Primary outcome
Rate of new stroke within 90 days
7.3%
9.2%
9.2 %
6.9 %
4.6 %
2.3 %
0.0 %
Clopidogrel-aspirin
Aspirin
Significant
decrease ▼
NNT = 52
Significant decrease in the rate of new stroke within 90 days (7.3% vs. 9.2%; HR 0.79, 95% CI 0.66 to 0.94).
Secondary outcomes
Significant decrease in cardiovascular event (7.5% vs. 9.3%; HR 0.8, 95% CI 0.67 to 0.96).
Significant decrease in ischemic stroke (6.8% vs. 9%; HR 0.75, 95% CI 0.63 to 0.9).
Significant decrease in TIA (0.7% vs. 1.3%; HR 0.54, 95% CI 0.32 to 0.91).
Safety outcomes
No significant differences in bleeding, hepatotoxic effects, muscle toxic effects, death from any cause.
Significant difference in moderate-to-severe bleeding (0.9% vs. 0.4%).
Conclusion
In patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy, clopidogrel-aspirin was superior to aspirin with respect to the rate of new stroke within 90 days.
Reference
Ying Gao, Weiqi Chen, Yuesong Pan et al. Dual Antiplatelet Treatment up to 72 Hours after Ischemic Stroke. N Engl J Med. 2023 Dec 28;389(26):2413-2424.
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