Dual Antiplatelet Therapy for Lacunar Infarct
Dual antiplatelet therapy (aspirin plus clopidogrel) is NOT recommended for patients with lacunar infarct, as it significantly increases bleeding risk and mortality without reducing recurrent stroke.
Evidence Against DAPT in Lacunar Stroke
The definitive evidence comes from the SPS3 trial, which specifically studied patients with recent lacunar infarcts 1. This landmark study demonstrated that:
No stroke reduction benefit: Adding clopidogrel 75 mg to aspirin 325 mg daily did not significantly reduce recurrent stroke risk (2.5% per year with DAPT vs 2.7% per year with aspirin alone; hazard ratio 0.92,95% CI 0.72-1.16) 1
Nearly doubled bleeding risk: Major hemorrhage occurred in 2.1% per year with DAPT compared to 1.1% per year with aspirin alone (hazard ratio 1.97,95% CI 1.41-2.71; P<0.001) 1
Increased mortality: All-cause mortality was significantly higher with DAPT (hazard ratio 1.52,95% CI 1.14-2.04; P=0.004), and this excess mortality was not explained by fatal hemorrhages alone 1
Guideline Recommendations
The American College of Chest Physicians guidelines explicitly state that dual antiplatelet therapy was "not proven successful when compared with aspirin alone in stable patients at high risk for atherothrombotic events or with clopidogrel alone in patients after a recent ischemic stroke or TIA" 2.
The 2010 ACC/AHA consensus document confirms that "patients with recent ischemic stroke or transient ischemic attack treated with clopidogrel plus aspirin had an insignificant reduction in major CV events (16.7% to 15.7%) compared with aspirin alone and experienced more life-threatening hemorrhages (1.3% to 2.6%)" 2.
Recommended Antiplatelet Strategy
Use single antiplatelet therapy with either:
- Aspirin 75-325 mg daily (most commonly used) 3
- Clopidogrel 75 mg daily as an alternative if aspirin is contraindicated 3
The FDA-approved indication for clopidogrel specifically includes "patients with established peripheral arterial disease or with a history of recent myocardial infarction (MI) or recent stroke" as monotherapy to reduce the rate of MI and stroke 3.
Important Distinction: When DAPT IS Indicated
DAPT with aspirin plus clopidogrel IS indicated for:
- Acute coronary syndromes (both STEMI and NSTEMI) for 12 months 2, 3
- Recent coronary stent placement (minimum 1 month for bare-metal stents, 12 months for drug-eluting stents) 2
- High-risk TIA or minor ischemic stroke (NOT lacunar) when initiated within 24-72 hours for 21-30 days 4, 5
Emerging Evidence with Cilostazol
One recent study (CSPS.com subanalysis, 2023) suggested potential benefit of DAPT using cilostazol (not clopidogrel) combined with aspirin or clopidogrel in chronic lacunar stroke patients 6. However, this represents a different drug combination and requires validation before changing practice, as cilostazol has a different mechanism of action than clopidogrel 6.
Common Pitfalls to Avoid
- Do not extrapolate ACS or coronary stenting DAPT guidelines to lacunar stroke patients—the pathophysiology and evidence base are completely different 1
- Do not assume that more antiplatelet therapy is better—the SPS3 trial definitively showed harm with DAPT in lacunar stroke 1
- Do not confuse lacunar stroke with large-vessel atherosclerotic stroke or cardioembolic stroke, which may have different treatment considerations 1