POINT
Trial question
What is the effect of combination antiplatelet therapy with clopidogrel and aspirin in patients with minor ischemic stroke or high-risk TIA?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
45.0% female
55.0% male
N = 4881
4881 patients (2195 female, 2686 male).
Inclusion criteria: patients with minor ischemic stroke or high-risk TIA.
Key exclusion criteria: thrombolytic therapy within 1 week before the event, candidates for thrombolysis, endovascular therapy, or endoarterectomy, planned use of antiplatelet therapy or anticoagulation therapy, contraindication to aspirin or clopidogrel.
Interventions
N=2432 dual antiplatelet therapy (clopidogrel at a loading dose of 600 mg on day 1, followed by 75 mg per day plus aspirin at a dose of 50-325 mg per day).
N=2449 aspirin alone (at a dose of 50-325 mg per day plus matched placebo).
Primary outcome
Major ischemic events at 90 days
5%
6.5%
6.5 %
4.9 %
3.3 %
1.6 %
0.0 %
Dual antiplatelet
therapy
Aspirin
alone
Significant
decrease ▼
NNT = 66
Significant decrease in major ischemic events at 90 days (5% vs. 6.5%; HR 0.75, 95% CI 0.59 to 0.95).
Secondary outcomes
Significant decrease in ischemic stroke (4.6% vs. 6.3%; HR 0.72, 95% CI 0.56 to 0.92).
Significant decrease in total ischemic or hemorrhagic stroke (4.8% vs. 6.4%; HR 0.74, 95% CI 0.58 to 0.94).
No significant difference in ischemic stroke, MI, death from ischemic vascular causes, or major hemorrhage (5.8% vs. 6.8%; HR 0.84, 95% CI 0.67 to 1.05).
Safety outcomes
No significant differences in the rates of hemorrhagic stroke, symptomatic intracerebral hemorrhage, or other symptomatic ICH and death from hemorrhagic vascular causes.
Significant differences in major hemorrhage (0.9% vs. 0.4%, p = 0.02; HR 2.32, 95% CI 1.10-4.87) and minor hemorrhage (1.6% vs. 0.5%, p = 0.002; HR 3.12, 95% CI 1.67-5.83.
Conclusion
In patients with minor ischemic stroke or high-risk TIA, dual antiplatelet therapy was superior to aspirin alone with respect to major ischemic events at 90 days.
Reference
Johnston SC, Easton JD, Farrant M et al. Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA. N Engl J Med. 2018 Jul 19;379(3):215-225.
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