He said that the dramatic benefit of the combination therapy was surprising because the genetics of the Chinese make it more difficult to metabolize clopidogrel. Therefore, he said, “the benefit of the therapy in the US could be even stronger but bleeding risk might also be greater.”
In addition to the CHANCE trial, the Platelet-Oriented Inhibition in New TIA (POINT) study is ongoing in the US, Dr. Johnston noted. The POINT study, for which he is a lead investigator, is using a higher loading dose of clopidogrel (600 mg) and the investigators are beginning treatment within the first 12 hours of TIA or minor stroke onset. (For more on the trial, which is being sponsored by the National Institute of Neurological Disorders and Stroke, see http://1.usa.gov/138cT8T.)
“It is wonderful to have a positive trial in stroke treatment,” said Dr. Johnston. “If the numbers are right, a combination treatment could prevent tens of thousands of strokes a year. We haven't had a solidly positive stroke trial in a long time.” He cautions, however, that the study findings must be replicated in the on-going trials.
EXPERTS WEIGH IN
In a commentary accompanying the study, Graeme J. Hankey, MD, a stroke expert at the University of Western Australia and Royal Perth Hospital, noted that the CHANCE investigators “completed a large, scientifically rigorous trial that proves the concept that dual antiplatelet therapy can be more effective than single antiplatelet therapy in preventing early recurrent stroke in patients with acute symptomatic atherothrombosis (predominantly intracranial) of the brain.”
But he noted that the CHANCE investigators had to screen 41,561 patients with stroke or TIA to find 5,170 appropriate patients (12.4 percent), suggesting that 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,” he said.
Ralph L. Sacco MD, professor and Olemberg chair of neurology and executive director of the McKnight Brain Institute and chief of neurology at Jackson Memorial and Miller School of Medicine at the University of Miami, agreed that the study findings are “convincing. However, clopidogrel and aspirin have not been found to be efficacious in the long-term treatment for prevention of stroke recurrence in a variety of trials and can increase the risk of bleeding.”
“This trial offers hope that the short-term combination antiplatelets may be worth the increased bleeding risk to improve outcomes,” he said. “Other studies continue to assess this more aggressive antiplatelet option among US patients since Chinese patients could have different stroke subtypes and higher risks of recurrence.”
Robert G. Hart, MD, a professor of medicine (neurology) at McMaster University's Population Health Research Institute in Hamilton, Ontario, agreed. “An important study, to be sure. The controversy is whether the results can be generalized to North American patients (since there is the suspicion that strokes in China are due to a different spectrum of cerebrovascular disorders).”
He pointed out that results from the POINT study in North America are two to four years away (unless stopped early for efficacy).
McMaster University's Michael Sharma, MD, associate professor of medicine (neurology), added that other antiplatelet therapies have been tried unsuccessfully in stroke. He said the incidence of subsequent stroke in the Chinese study population was higher than it is in the US. In areas surrounding major stroke centers, the 90-day stroke rate is 3 to 5 percent, down from 10 percent. “Maybe we are seeing different types of patients,” he said. “People in China, Korea, and Japan have higher rates of intracranial atherosclerosis, and that is more amenable to dual antiplatelet therapy.”
Also, he said, the clinicians selected TIA patients for the study who were at high risk, which could have strengthened the study effects. They recruited patients with ABCD2 scores of four or higher and NIH Stroke Scale scores under four.
He said that “if the treatments are used in tandem, neurologists must be careful to select the high-risk patient and then begin treatment within the first 24 hours.”
Dr. Sharma pointed out that diagnosing TIA is challenging. About 40 percent of the patients referred to stroke centers with the diagnosis did not have a TIA, he pointed out, adding that ABCD2 is good at screening out individuals who do not have TIA.
The US study — POINT — “will be very important in confirming what we see in our patients and how big the benefit is,” he added.
LINK UP FOR MORE INFORMATION:
•. Wang Y, Wang Y, Zhao Z for the CHANCE Investigators. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med 2013;369(1):1–9. E-pub 2013 Jun 26.
•. Neurology Clinical Practice
: Practice Across Borders — Standard strategies for acute ischemic stroke within the rtPA therapeutic window: “http://bit.ly/1buvzrA
© 2013 American Academy of Neurology
•. Neurology Clinical Practice
: Practice Across Borders — Standard strategies for acute ischemic stroke within the rtPA therapeutic window, United States: http://bit.ly/15AFCbK
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