Lacunar Stroke Does Not Justify Long-term Dual Antiplatelet Therapy

Hooman Kamel, MD


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In This Article

Abstract and Introduction


In the SPS3 trial, clopidogrel added to aspirin increased bleeding and mortality without providing a compensatory benefit.


Long-term dual antiplatelet therapy has not been rigorously assessed in patients with specific ischemic stroke subtypes other than that associated with atrial fibrillation (JW Neurol Aug 11 2009).

The antiplatelet arm of the multicenter Secondary Prevention of Small Subcortical Strokes (SPS3) trial was designed to compare aspirin with or without clopidogrel specifically in patients with lacunar stroke — a small subcortical infarct caused by intrinsic small-vessel disease.

Patients qualified for SPS3 if they were aged ≥30 and had experienced a recent symptomatic lacunar stroke, defined as a typical clinical syndrome along with a compatible magnetic resonance imaging lesion. At a median of about 2 months after the qualifying stroke, 3020 patients were randomized to aspirin (325 mg daily) and either clopidogrel (75 mg daily) or placebo. Researchers followed patients for an average of 3.4 years and the trial was stopped 10 months early because of futility and evidence of harm in the dual antiplatelet group.

The composite primary outcome of any ischemic stroke or intracerebral hemorrhage occurred at an annual rate of 2.5% with aspirin plus clopidogrel versus 2.7% with aspirin alone — a nonsignificant difference. Lacunar strokes were the most common type of recurrent ischemic stroke (71%) and occurred with essentially equal frequency in both groups. Dual antiplatelet therapy significantly increased the risks for major hemorrhage (hazard ratio, 1.97) and death (HR, 1.52) compared with aspirin alone.