July 10, 2013
Chinese Study: Two-Drug Combo Reduces Risk
of Subsequent Strokes

San Francisco—The risk of subsequent stroke was decreased by almost a third when a simple drug regimen of two anticlotting drugs—clopidogrel and aspirin—was administered instead of standard therapy to patients who previously had minor or transient stroke symptoms.

That’s according to a recent phase III clinical trial, which involved multiple sites in China and which was reported recently in the New England Journal of Medicine.

The joint trial, which was conducted in the U.S. by researchers from China and the University of California, San Francisco (UCSF), involved 5,170 patients hospitalized after suffering minor ischemic strokes or transient ischemic attacks (TIAs). For a period of 3 months, considered the most critical time for addressing minor stroke or TIA, study subjects were randomized and treated with either aspirin alone or aspirin plus clopidogrel, marketed as Plavix.

Results indicated that, overall, 8.2% of patients taking both drugs suffered subsequent strokes in the 3 months of follow-up compared to 11.7% of patients taking aspirin alone.

“The results were striking,” said senior author S. Claiborne Johnston, MD, PhD, a professor of neurology and associate vice chancellor of research at UCSF.

Johnston noted that the Chinese trial, called CHANCE (Clopidogrel in High-risk Patients with Acute Non-disabling Cerebrovascular Events), is nearly identical to a National Institutes of Health–sponsored trial that is already enrolling patients in the U.S., including at UCSF, called POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke).

“If POINT confirms CHANCE, then we’re done—the two-drug combination becomes the standard of care,” he said. “Anybody with a transient ischemic attack or minor stroke will get clopidogrel plus aspirin.”

Johnston, who also is the principal investigator of the POINT trial, cautioned that the U.S. trial is still critical, because genetics, risk factors, and medical practice all could vary from Chinese subjects.

While finding that results “show that dual antiplatelet therapy can be given without excess harm in patients with acute focal brain ischemia, provided that patients have a low risk of hemorrhagic transformation—no fresh brain infarction (i.e., TIA) or a very small volume of fresh brain infarction (i.e., minor ischemic stroke),” study authors note that 41,561 patients with stroke or TIA had to be screened to find 5,170 appropriate patients

“Hence, 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,” they write. “The results may also 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 prevalence of genetic polymorphisms of liver cytochrome P-450 (CYP) isozymes, which metabolize clopidogrel to its active metabolites.”

An accompanying editorial by Graeme J. Hankey, MD, FRACP, FRCP, of Royal Perth Hospital in Western Australia, called the CHANCE results “Impressive.”

He called for additional ongoing large clinical trials of the safety and efficacy of dual and triple antiplatelet therapy in non-Chinese subjects.

“Moreover, I hope that researchers will evaluate new antiplatelet agents (e.g., ticagrelor and prasugrel) and new anticoagulant agents (e.g., rivaroxaban) that are effective in atherothrombotic acute coronary syndrome in patients with acute TIA and minor ischemic stroke due to arterial thromboembolism,” Hankey writes.

U.S. Pharmacist Social Connect