Dual Antipletelet Therapy Is Beneficial in Mild Ischemic Stroke

Among patients with mild ischemic stroke or transient ischemic attack, dual antiplatelet therapy with clopidogrel and aspirin vs aspirin alone is beneficial when initiated within 72 hours of symptom onset; however, there is still a similar risk for moderate to severe bleeding, according to study results published in JAMA Network Open

Researchers conducted a subgroup analysis sourcing data from the Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis (INSPIRES; ClinicalTrials.gov Identifier: NCT03635749) study, which was a double-blind, placebo-controlled, multicenter, 2-by-2 factorial randomized clinical trial conducted at 222 hospitals in China between September 2018 and October 2022. This analysis aimed to determine whether dual antiplatelet therapy with clopidogrel and aspirin is effective when initiated up to 72 hours following mild ischemic stroke and transient ischemic attack. Patients with acute mild ischemic stroke and transient ischemic attack were categorized into 3 subgroups (ie, group 1: ≤24 hours; group 2: >24 to ≤48 hours; group 3: >48 to 72 hours) based on time from symptom onset to random assignment and randomly assigned 1:1 to receive clopidogrel combined with aspirin or placebo combined with aspirin. The primary efficacy outcome was new stroke within 90 days and the safety outcome of interest was moderate to severe bleeding per the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria. Cox proportional hazards and log-normal regression models were used in statistical analyses.

A total of 6100 patients (median age, 65; men, 64.2%) were included in the INSPIRE trial, of whom 3050 received clopidogrel-aspirin and 3050 received aspirin alone. Groups 1, 2, and 3 comprised 783 (12.8%), 2552 (41.8%), and 2765 (45.3%) patients, respectively. Four patients in the clopidogrel-aspirin group and 2 patients in the aspirin alone group were lost to follow-up and 7 patients were missing data.

In groups 1, 2, and 3, new stroke within 90 days occurred in 97 (12.4%), 211 (8.3%), and 193 (7.0%) patients, respectively. Compared with group 1, groups 2 (hazard ratio [HR], 0.64; 95% CI, 0.50-0.81; P <.001) and 3 (HR, 0.52; 95% CI, 0.41-0.67; P <.001) had lower risk for new stroke within 90 days after adjusting for confounding factors.

Patients who received clopidogrel plus aspirin vs aspirin alone had a lower risk for new stroke within 90 days in each of the following groups:

• Group 1: 11.5% vs 13.4% (HR, 0.83; 95% CI, 0.55-1.25);
• Group 2: 7.6% vs 8.9% (HR, 0.85; 95% CI, 0.65-1.12); and,
• Group 3: 5.8% vs 8.2% (HR, 0.70; 95% CI, 0.53-0.94).

Risk for new stroke may be reduced by clopidogrel plus aspirin by 15% when initiated more than 24 hours to 48 hours and by 30% when initiated within more than 48 hours to 72 hours following the onset of symptoms.

In those with time to randomization of within 24 hours (group 1), moderate to severe bleeding occurred in 6 (1.5%) patients in the clopidogrel combined with aspirin group and 3 (0.8%) patients in the aspirin alone group (HR, 1.57; 95% CI, 0.36-6.83).

Among patients in group 2, moderate to severe bleeding occurred in 9 (0.7%) and 4 (0.3%) patients in the clopidogrel plus aspirin and aspirin alone groups, respectively (HR, 2.25; 95% CI, 0.68-7.39).

Within group 3, moderate to severe bleeding occurred in 12 (0.9%) patients in the clopidogrel plus aspirin group and 6 (0.4%) patients in the aspirin alone group (HR, 2.00; 95% CI, 0.73-5.43).

Study limitations include the exploratory design, exclusion of certain patients with ischemic stroke, and inconsistencies in patient enrollment due to protocol changes.

“Patients should receive dual antiplatelet therapy with clopidogrel and aspirin within 72 hours after symptom onset,” the researchers concluded.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.