We conducted a double-blind, multicenter trial involving 3020 patients with recent symptomatic
lacunar infarcts identified by magnetic resonance imaging. Patients were randomly assigned to receive 75 mg of
clopidogrel or placebo daily; patients in both groups received 325 mg of
aspirin daily. The primary outcome was any recurrent
stroke, including
ischemic stroke and
intracranial hemorrhage.
RESULTS: The participants had a mean age of 63 years, and 63% were men. After a mean follow-up of 3.4 years, the risk of recurrent
stroke was not significantly reduced with
aspirin and
clopidogrel (dual antiplatelet
therapy) (125
strokes; rate, 2.5% per year) as compared with
aspirin alone (138
strokes, 2.7% per year) (hazard ratio, 0.92; 95% confidence interval [CI], 0.72 to 1.16), nor was the risk of recurrent
ischemic stroke (hazard ratio, 0.82; 95% CI, 0.63 to 1.09) or disabling or fatal
stroke (hazard ratio, 1.06; 95% CI, 0.69 to 1.64). The risk of major
hemorrhage was almost doubled with dual antiplatelet
therapy (105
hemorrhages, 2.1% per year) as compared with
aspirin alone (56, 1.1% per year) (hazard ratio, 1.97; 95% CI, 1.41 to 2.71; P<0.001). Among classifiable recurrent
ischemic strokes, 71% (133 of 187) were
lacunar strokes. All-cause mortality was increased among patients assigned to receive dual antiplatelet
therapy (77 deaths in the group receiving
aspirin alone vs. 113 in the group receiving dual antiplatelet
therapy) (hazard ratio, 1.52; 95% CI, 1.14 to 2.04; P=0.004); this difference was not accounted for by fatal
hemorrhages (9 in the group receiving dual antiplatelet
therapy vs. 4 in the group receiving
aspirin alone).
CONCLUSIONS: Among patients with recent
lacunar strokes, the addition of
clopidogrel to
aspirin did not significantly reduce the risk of recurrent
stroke and did significantly increase the risk of
bleeding and death. (Funded by the National Institute of Neurological Disorders and Stroke and others; SPS3 ClinicalTrials.gov number, NCT00059306.).