In Patients with Lacunar Strokes, Addition of Clopidogrel to Aspirin Does Not Reduce Risk of Recurrent Stroke
By Matthew E. Fink, MD. Professor and Chairman, Weill Cornell Medical College and Neurologist-in-Chief, New York Presbyterian Hospital. Matthew Fink, MD, is a retained consultant for MAQUET.
This article originally appeared in the October 2012 issue of Neurology Alert. It was peer reviewed by M. Flint Beal, MD. Dr. Beal is Anne Parrish Titzel Professor, Department of Neurology and Neuroscience, Weill Cornell Medical Center. Dr. Beal reports no financial relationships relevant to this field of study.
Source: The SPS3 Trial Investigators. Effects of clopidogrel added to aspirin in patients with recent lacunar stroke. N Engl J Med 2012;367:817-825.
Small subcortical brain infarcts, known as lacunar strokes, account for about 25% of all ischemic strokes. They are believed, in most cases, to be caused by disease of small penetrating arteries, i.e., lenticulostriate branches of the middle cerebral arteries, and are the most common cause of "silent" brain infarcts and vascular dementia. Lacunar infarcts were included in studies of intravenous thrombolysis, and they are treated with r-tPA within the appropriate time window. However, secondary prevention of lacunar strokes with antiplatelet therapies has not been specifically studied using MRI as a sensitive method to detect new infarcts.
The Secondary Prevention of Small Subcortical Strokes (SPS3) trial compared two randomized interventions, clopidogrel 75 mg with aspirin 325 mg vs aspirin 325 mg alone in patients who had a lacunar stroke (≤ 2 cm) within 180 days of enrollment. There were 3020 patients enrolled, with 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 dual antiplatelet therapy, compared to aspirin alone (2.5% per year vs 2.7% per year). The risk of major hemorrhage was almost doubled with dual antiplatelet therapy vs aspirin alone (2.1% per year vs 1.1% per year; hazard ratio [HR], 1.97). All-cause mortality was increased in the dual antiplatelet therapy group (hazard ratio, 1.52; 95% confidence interval, 1.14-2.04; P = 0.004), but this increase in mortality was NOT accounted for by fatal hemorrhages. In patients with lacunar stroke, the addition of clopidogrel to aspirin did not reduce the risk of recurrent ischemic stroke, but did increase the risk of serious bleeding and death.