Effects of Clopidogrel Added to Aspirin in Patients with Recent Lacunar Stroke

By O. Benavente, R. Hart, L. McClure, Jeffrey Szychowski, C. Coffey, L. Pearce. New England Journal of Medicine, 2012

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Background Lacunar infarcts are a frequent type of stroke caused mainly by cerebral small-vessel disease. The effectiveness of antiplatelet therapy for secondary prevention has not been defined. Methods 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.)

Subfields: Cardiology and Cardiovascular Medicine, Epidemiology, Neurology

View Paper: https://www.semanticscholar.org/paper/7428af0b5eb31a05994057f120540f203a5654f3

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Citations in the corpus

• Factors Influencing the Decline in Stroke Mortality (2013, result): “Results from the SPS3 trial indicated that a combination of clopidogrel plus aspirin in patients with small-vessel stroke led to reduction in stroke but was not significantly better than aspirin alone, and there was an increase in hemorrhagic complications.(80) These findings were consistent for the”
• Impact of Hypertension on Cognitive Function (2016, neutral): “The SPS3 antiplatelet arms were stopped early because of futility and evidence of harm.(255) Target populations for the trials differed.”
• Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. (2014, background): “In the recently published SPS3 trial, 3026 patients with MRI-confirmed lacunar stroke within 180 days were randomized to clopidogrel 75 mg plus aspirin 325 mg daily versus aspirin 325 mg daily.(7) The primary outcome measure was recurrent ischemic or hemorrhagic stroke, and a rate of 2.”