"Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA". The New England Journal of Medicine. Published May 16, 2018.

Clinical Question

Does the combination of clopidogrel and aspirin improve outcomes compared to aspirin alone in patients with minor ischemic stroke or high-risk TIA?

Bottom Line

In patients with minor ischemic stroke or high-risk TIA, the combination of clopidogrel and aspirin reduced the risk of major ischemic events but increased the risk of major hemorrhage at 90 days compared with aspirin alone.

Major Points

Guidelines

Design

- Multicenter, double-blind, parallel-group, randomized, placebo-controlled trial
- N=4,881 patients
- Clopidogrel + aspirin vs. aspirin alone
- Enrolment: May 28, 2010, to December 19, 2017
- Follow-up: 90 days

Population

- At least 18 years of age
- Had a minor ischemic stroke (NIHSS score ≤3) or high-risk TIA (ABCD2 score ≥4) within 12 hours prior
- Underwent imaging to rule out intracranial hemorrhage or other mimics
- Major exclusions: Candidates for thrombolysis/thrombectomy, contraindication to aspirin or clopidogrel, anticipated need for NSAID use beyond 7 days

Interventions

- Clopidogrel (600 mg on day 1, followed by 75 mg per day) + aspirin (50 to 325 mg per day) vs. aspirin alone (same dose range)

Outcomes

- Primary efficacy outcome: Composite of ischemic stroke, myocardial infarction, or death from ischemic vascular causes at 90 days
- Major hemorrhage was the primary safety outcome

Criticisms

- Lower-than-expected overall event rates, particularly in TIA patients with low ABCD2 scores
- The study population did not represent moderate-to-severe stroke, cardioembolic stroke, or candidates for thrombolysis/thrombectomy

Funding

- National Institute of Neurological Disorders and Stroke
- Sanofi provided clopidogrel and placebo for 75% of patients

Further Reading