Clopidogrel Plus Aspirin Tops Aspirin Alone in Reducing Stroke in High-Risk Patients

In patients with recent transient ischemic attack (TIA) or acute minor stroke, dual antiplatelet therapy with clopidogrel plus aspirin reduced the risk of stroke by 32 percent compared to therapy with aspirin alone, according to results from the CHANCE trial, published June 26 in the New England Journal of Medicine.

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The randomized, double-blind, placebo-controlled trial was conducted at 114 centers in China. Using 5,170 patients at high risk for recurrent ischemia and low risk for hemorrhage, patients were randomly assigned to combination therapy – with clopidogrel at an initial dose of 300 mg, followed by 75 mg per day for 90 days, plus aspirin at a dose of 75 mg per day for the first 21 days – or to placebo plus aspirin – 75 mg per day for 90 days. Treatment was begun within 24 hours of the onset of symptoms, and results showed that stroke occurred in 8.2 percent of patients in the clopidogrel-aspirin group, as compared to 11.7 percent in the aspirin group (HR 0.68, 95 percent CI. 0.57 to 0.81; p<0.001). Further, there was no difference in risk of hemorrhage between the two groups. In addition, the event rates during this early period were very high, and clopidogrel was associated with an absolute risk reduction of 3.5 percentage points, equivalent to a number needed to treat 29 patients to prevent one stroke over a period of 90 days.

The authors conclude that "among patients with TIA or minor stroke who can be treated within 24 hours after the onset of symptoms, the combination of clopidogrel and aspirin is superior to aspirin alone for reducing risk of stroke within the first 90 days and does not increase risk of hemorrhage."

In an accompanying editorial, Graeme Hankey, MBBS, MD, University of Western Australia, praised the rigor of the trial, but cautioned that results couldn't be generalized to most patient populations because investigators selected a very specific, high-risk cohort for their study. He also noted that the results might not apply to non-Chinese populations with different forms of underlying arterial disease and different prevalences of genetic polymorphisms in cytochrome P-450 isozymes, which metabolize clopidogrel to its active forms.

"The implication of this trial is that Chinese patients with acute TIA or minor ischemic stroke who are at high risk for recurrence should be regarded as a medical emergency," Dr. Hankey said. "They should be treated immediately with clopidogrel plus aspirin."

Dr. Hankey advised clinicians with non-Chinese patients with acute TIA or minor ischemic stroke to enroll them into to the similar POINT and TARDIS trials. He also called on researchers to evaluate newer antiplatelet agents in patients with acute TIA and minor ischemic stroke due to arterial thromboembolism.

Keywords: Prevalence, Thromboembolism, Isoenzymes, Stroke, China, Polymorphism, Genetic, Ischemic Attack, Transient, Platelet Aggregation Inhibitors, Cytochromes, Hemorrhage

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