Clopidogrel and Aspirin May Reduce Risk of Recurrent Stroke

HONOLULU—A combination of clopidogrel and aspirin may reduce the overall three-month risk of ischemic stroke and hemorrhagic stroke by about 32%, compared with aspirin alone, if administered within 24 hours of a minor stroke or transient ischemic attack (TIA), according to research presented at the 2013 International Stroke Conference. Most of the treatment effect is evident within the first few days after initiation, which confirms the importance of treating patients with stroke acutely, said S. Claiborne Johnston, MD, PhD, Professor of Neurology and Director of the Stroke Service at the University of California, San Francisco, who presented the trial along with principal investigator Yongjun Wang, MD, Professor of Neurology at Beijing TianTan Hospital, Capital Medical University.

Comparing Treatment Regimens in Chinese Patients With Stroke
In the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) study, Dr. Johnston and colleagues randomized 5,170 patients with TIA or minor stroke to clopidogrel and aspirin or aspirin alone. Eligible participants were adults with nondisabling ischemic stoke, defined by an NIH Stroke Scale score of 3 or lower, or a high-risk TIA, defined by an ABCD2 (age, blood pressure, clinical features, duration of TIA, and diabetes) score of 4 or greater. Subjects were enrolled at 114 medical centers in China.

Patients randomized to aspirin received 75 to 300 mg of aspirin on the first day and 75 mg daily for 20 additional days, in addition to placebo. Subjects randomized to clopidogrel and aspirin received the same aspirin regimen plus a 300-mg load of clopidogrel on the first day and daily 75-mg doses of clopidogrel for 89 days. Treatment was begun within 24 hours of symptom onset.

The primary end point was ischemic or hemorrhagic stroke at three months. The researchers also chose a composite end point of clinical vascular events, including ischemic stroke, hemorrhagic stroke, myocardial infarction, and vascular death, at three months. Hemorrhage was foremost among the study's safety outcomes.

Drug Combination May Not Affect Hemorrhage Rate
The investigators observed no demographic differences between the two treatment groups. Women accounted for approximately 33% of the study population, which reflects the proportion of patients who present with TIA, minor stroke, or major stroke at hospitals in China, said Dr. Johnston. Minor stroke was more common than TIA in the study population, although the researchers had intended to enroll an equal number of patients with each condition.

Stroke occurred in 8.2% of patients in the clopidogrel and aspirin group, compared with 11.7% of patients in the aspirin group. Rates of moderate or severe hemorrhage, hemorrhagic stroke, myocardial infarction, and cardiovascular death were the same in both treatment arms.

"We did not see any signal that suggests that the combination is unsafe," said Dr. Johnston. The rate of severe or moderate bleeding was the same for both patient groups. The investigators observed an insignificantly higher rate of mild bleeding (eg, nosebleed or bruising) in the clopidogrel group.

One important difference between care in China and care in North America and Europe may have affected the trial results. "About two-thirds of patients [in China] have hypertension, but less than 50% of them are on any drug for hypertension during follow-up, suggesting that the others were left untreated," said Dr. Johnston. "Similar kinds of numbers exist for diabetics and for dyslipidemia. Undertreatment is a big issue in China and it could impact the absolute effect size seen in the trial and the potential to see an effect," he added.

The CHANCE Study
The CHANCE study will continue for one year, and the investigators will examine whether the difference in outcomes between the two treatment arms persists for that time period, said Dr. Johnston. The researchers will assess patients' cognition at the final follow-up.

Various ancillary studies will also be conducted, including an investigation of serum and imaging biomarkers. In another ancillary study, the investigators will categorize patients based on vascular imaging to determine whether the treatment effect of clopidogrel and aspirin is larger in patients with intracranial atherosclerosis. "We know that intracranial atherosclerosis is a more important cause of TIA and stroke in this population," said Dr. Johnston.