June 26th, 2013

Some Patients with Minor Stroke or TIA May Benefit from Early Clopidogrel and Aspirin

Some people with minor ischemic stroke or transient ischemic attack (TIA) may benefit from dual antiplatelet therapy with aspirin and clopidogrel, according to a large new study from China published in the New England Journal of Medicine.

In the immediate period following a TIA or minor stroke, people are at high risk for having a major stroke. Aspirin is known to cause a modest reduction in recurrent events. More potent antiplatelet agents like clopidogrel may also be beneficial, but they have not been well studied in the early phase and may increase the risk for bleeding complications, including the conversion of an ischemic stroke into a worse hemorrhagic stroke.

Investigators in the CHANCE (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events) trial randomized 5170 patients within 24 hours of a minor ischemic stroke or high-risk TIA to 3 months of treatment with either clopidogrel and aspirin or placebo and aspirin. At 90 days, the rate of stroke was 8.2% in the combination group versus 11.7% in the aspirin-alone group (hazard ratio 0.68, CI 0.57-0.81, p<0.001). There were also significant reductions in the rates of fatal or disabling stroke and ischemic stroke.

There was no difference in moderate or severe hemorrhage, which occurred in 0.3% of patients in each group. Bleeding complications of any type occurred in 2.3% of the combination group versus 1.6% of the aspirin group (HR 1.41, CI 0.95-2.10, p=0.09). The investigators calculated that 29 patients would need to be treated to prevent one stroke in the 3-month period.

The authors speculate that their results were achieved because they “targeted a population at particularly high risk for recurrent ischemia and at low risk for hemorrhage.” Earlier trials had included patients with more severe strokes and had not studied patients in the very early period studied in CHANCE. The investigators note that most of the benefit occurred in the first few days.

In an accompanying editorial, Graeme Hankey praises the study but cautions that its results are not widely applicable, since more than 41,000 patients were screened to obtain the study population of 5200 patients. Because of this, he writes, the results “cannot be generalized to most patients; the study excluded patients with major ischemic stroke, who are at risk for hemorrhagic transformation, and patients with TIA due to isolated sensory, visual, or vertiginous syndromes, who are at low risk for recurrence.”

In addition, accoridng to Hankey, “the results may not apply to non-Chinese patients with different forms of underlying arterial disease (e.g., a higher prevalence of extracranial large-artery atherosclerosis) and different prevalences of genetic polymorphisms of liver cytochrome P-450 (CYP) isozymes, which metabolize clopidogrel to its active metabolites.”

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