New findings by McMaster University researchers contradict（反驳，否定） earlier reports that people with a certain genetic² make-up don't benefit from the blood-thinner clopidogrel（氯吡格雷） , also known as Plavix. After researchers from the United States, France and Germany reported clopidogrel is less effective in some patients, the Food and Drug Administration (FDA) in the United States issued a black box warning to physicians on the drug's package insert.

"(Our findings) add a further layer of complexity³ to the FDA 'black box' warning and show that reported genetic variants⁴（变体） have no effect in certain patient populations," said Dr. Guillaume Paré, lead researcher and assistant professor of pathology（病理学） and molecular⁵ medicine at the Michael G. DeGroote School of Medicine.

Clopidogrel is the world's second best-selling prescription⁶ drug（处方药） with global sales of more than $6 billion annually⁷. It is used in 110 countries by millions of people to reduce the risk of heart attack and stroke.

Following the FDA's warning, clopidogrel became the focus of on-going debates within cardiology（心脏病学） circles. Some American cardiologists initially⁸ called the FDA's actions irresponsible. Others complained they were left without any appropriate direction on how to manage their patients.

About 20 per cent of the population carry the loss-of-function version of the gene¹ involved in the clopidogrel controversy⁹.

To assess the influence genetics might have on patients prescribed clopidogrel, Paré and colleagues from McMaster University conducted a genetic sub-study of 6,000 participants from two major clinical trials (CURE and ACTIVE). The CURE (Clopidogrel in Unstable¹⁰ Angina to Prevent Recurrent Ischemic Events) trial of 12,562 patients with acute coronary（冠状的） syndrome¹¹（综合症） in 28 countries found clopidogrel significantly reduces the risk of heart attack stroke and dying. The ACTIVE (Atrial Fibrillation Clopidogrel Trial with Irbesartan for the Prevention of Vascular¹² Events) trial of 7,554 patients with atrial fibrillation（心房颤动） in 30 countries found clopidogrel added to Aspirin¹³ significantly reduced the risk of cardiovascular events, and particularly stroke. Both trials were supported by Sanofi-Aventis and Bristol-Myers Squibb.

"We found the previously¹⁴ reported genetic variants had no effect at all (for patients) in either the CURE or ACTIVE trials," said Paré. He will present these findings at the European Cardiovascular Society Congress meeting in Stockholm, Sweden, on August 29. The study will also be simultaneously¹⁵（同时地） published online in the New England Journal of Medicine.

Paré said the positive results from McMaster's genetic sub-study come from studying different patient populations. "Also, our study design was a bit stronger from an epidemiology（流行病学） point of view."

Beyond clopidogrel, he said there is a broader message of the need for cautiousness as genetics becomes more and more integrated into patient care.