Adding clopidogrel does not reduce the risk of recurrent stroke in patients with a recent lacunar stroke who were taking aspirin, a subanalysis of a randomized, controlled clinical trial found.

Robert Cote, MD, of McGill University in Montreal, and colleagues conducted a post hoc analysis of the Secondary Prevention and Small Subcortical Strokes Trial (SPS3), which included patients with a recent symptomatic lacunar stroke confirmed by neuroimaging. Patients in the main SPS3 study were randomized to single or dual antiplatelet therapy or one of two target levels for blood pressure control.

The subanalysis, published online Jan. 2 in Neurology, included the 838 patients on aspirin only at the time of the qualifying event. Of those “aspirin failures” at baseline, 411 were treated with aspirin plus placebo and 427 with aspirin plus clopidogrel (Plavix, Bristol Myers-Squibb/Sanofi Aventis). Patients in the subanalysis were followed for an average of 3.5 years.

Compared with SPS3 patients not taking aspirin, the aspirin failure group was older and had a higher annual risk of recurrent strokes (3.2 percent vs. 2.3 percent).

In the subanalysis, patients on the aspirin/placebo and aspirin/clopidogrel groups had similar rates of all recurrent stroke (3.3 percent vs. 3.1 percent), ischemic stroke, intracranial hemorrhage or other major vascular events. The addition of clopidogrel did not reduce the composite outcome of stroke, MI or vascular death.

“This lack of protective benefit was observed even though this subgroup had a higher risk profile for ischemic stroke, with a relative risk increase of 30%, compared to the average patient in the main SPS3 trial,” Cote and colleagues wrote.

The risks of all-cause mortality and of gastrointestinal bleeding were twice as high in the aspirin/clopidogrel group compared with aspirin only group. The finding was similar to results in the main SPS3 study.

Cote and colleagues cautioned that the subanalysis results apply only to patients with lacunar stroke and not to other subtypes of ischemic stroke. They proposed that the findings provide Class 1 evidence for stroke prevention guidelines.

“[O]ur study … provides a partial answer to the question about the long-term potential value of choosing an alternate antiplatelet approach in patients who have had a cerebral ischemic event while receiving aspirin,” they wrote.