Related Experiment Video
Updated: May 4, 2026
Catheter Ablation in Combination With Left Atrial Appendage Closure for Atrial Fibrillation
Published on: February 26, 2013
ASA failure: does the combination ASA/clopidogrel confer better long-term vascular protection?
Robert Côté1, Yu Zhang, Robert G Hart
1From the Department of Neurology, Neurosurgery and Medicine (R.C.), McGill University, Montreal, Canada; Department of Biostatistics (Y.Z., L.A.M.), University of Alabama at Birmingham; Department of Medicine (Neurology) (R.G.H.), McMaster University, Hamilton, Canada; Hennepin County Medical Center (Neurology) (D.C.A.), University of Minnesota Medical School, Minneapolis; Department of Clinical Pharmacy (R.L.T.), University of Texas, Austin; and Department of Medicine (O.R.B.), Brain Research Center, University of British Columbia, Vancouver, Canada.
Insights
Adding clopidogrel to aspirin (ASA) did not reduce recurrent stroke risk in patients with lacunar stroke. Dual antiplatelet therapy increased gastrointestinal bleeding risk without improving vascular outcomes.
Area of Science:
- Neurology
- Cardiology
- Clinical Trials
Background:
- Lacunar stroke is a significant cause of disability.
- Acetylsalicylic acid (ASA) is a standard treatment, but some patients experience ASA failure.
- The role of dual antiplatelet therapy in this population requires further investigation.
Purpose of the Study:
- To evaluate the long-term vascular protective effect of adding clopidogrel to aspirin in patients with lacunar stroke and ASA failure.
- To assess the impact on stroke recurrence and major hemorrhage events.
Main Methods:
- Post hoc analysis of 838 patients from the Secondary Prevention of Small Subcortical Strokes Trial (SPS3).
- Patients with ASA failure and recent lacunar stroke were randomized to aspirin plus clopidogrel or aspirin alone.
- Primary outcome: stroke recurrence; Safety outcome: major extracranial hemorrhage. Mean follow-up: 3.5 years.
Main Results:
- The risk of recurrent stroke was similar between the dual antiplatelet group (3.1% per year) and the aspirin-only group (3.3% per year).
- No significant difference in ischemic stroke recurrence was observed between the groups.
- Dual antiplatelet therapy led to a higher risk of gastrointestinal bleeding (HR 2.7) but not intracranial hemorrhage.
Conclusions:
- Adding clopidogrel to aspirin does not reduce vascular events in patients with recent lacunar stroke who are already taking aspirin.
- Dual antiplatelet therapy in this specific patient group did not provide additional vascular protection compared to aspirin monotherapy.
- The increased risk of gastrointestinal bleeding with dual therapy outweighs potential benefits in this population.
Objective:
To assess whether adding clopidogrel to acetylsalicylic acid (ASA) has a long-term protective vascular effect in patients with lacunar stroke while taking ASA.
Methods:
Post hoc analysis of 838 patients with ASA failure and recent lacunar stroke from the Secondary Prevention of Small Subcortical Strokes Trial (SPS3) cohort randomly allocated to aspirin (325 mg/day) and clopidogrel (75 mg/day) or placebo. Primary efficacy outcome was stroke recurrence (ischemic and intracranial hemorrhage) and main safety outcome was major extracranial hemorrhage. Patients were followed for a mean period of 3.5 years.
Results:
The ASA failure group had a significantly higher risk of vascular events including ischemic stroke when compared with the non-ASA failure group (n = 2,151) in SPS3 (p = 0.03). Mean age was 65.6 years and 65% were men. The risk of recurrent stroke was not reduced in the dual antiplatelet group, 3.1% per year, compared to the aspirin-only group, 3.3% per year (hazard ratio [HR] 0.91; 95% confidence interval [CI] 0.61-1.37). There was also no difference between groups for ischemic stroke (HR 0.90; 95% CI 0.59-1.38). The risk of gastrointestinal bleeding was higher in the dual antiplatelet group (HR 2.7; 95% CI 1.1-6.9); however, the risk of intracranial hemorrhage was not different.
Conclusions:
In patients with a recent lacunar stroke while taking ASA, the addition of clopidogrel did not result in reduction of vascular events vs continuing ASA only.
Classification Of Evidence:
This study provides Class I evidence that for patients with recent lacunar stroke while taking ASA, adding clopidogrel as compared to continuing ASA alone does not reduce the risk of recurrent stroke.
Related Concept Videos
01:20Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
01:27Peripheral Artery Disease III: Interprofessional Care
01:27Coronary Artery Disease V: Interprofessional Care
01:28Acute Coronary Syndrome IV: Interprofessional Care
01:26Atherosclerosis III: Management
01:29Venous Thrombosis III: Interprofessional Care