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Clopidogrel reduces death, stroke, heart attack now & later

July 1, 1993

DALLAS—The blood thinner clopidogrel, when used with aspirin, reduced the risk of subsequent heart attack, stroke and death in people who came to the emergency department with new or increasing chest pain or a heart attack, according to a report in a recent rapid access issue of Circulation: Journal of the American Heart Association.

Researchers also found that the drug’s benefits emerged within hours of administration and continued for up to a year when patients took it daily after hospital discharge.

“Other than aspirin, clopidogrel is the only antithrombotic (blood-thinning) agent that has shown a benefit both in the early phase and during long-term treatment of acute coronary syndromes,” says study co-author Shamir R. Mehta, M.D., assistant professor of medicine at McMaster University in Hamilton in Ontario, Canada. Acute coronary syndromes (ACS) include heart pain that is new or has worsened within the past few months (called unstable angina) or small heart attacks known as non-ST segment elevation heart attacks.

People who have ACS are at increased risk of subsequent cardiovascular events such as a heart attack, stroke or death. Currently, people with ACS are given aspirin to reduce their risk. Researchers in this study looked at whether adding clopidogrel to aspirin therapy would further benefit these high-risk patients.

Previous studies on clopidogrel have shown benefit in these patients, but the drug’s effects over this length of time have never been reported on such a large population, Mehta says.

Emergency department physicians in 28 countries participated in the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial, which involved 12,562 patients with unstable angina or non-ST segment elevation heart attack. Patients had an average age of 64, and 38 percent were women.

Patients in the study received either clopidogrel or placebo. All were treated with aspirin. Patients in the clopidogrel group received an immediate loading dose of 360 milligrams (mg) of the medication, followed by 75 mg each day for up to one year.

Researchers found that clopidogrel had a beneficial effect within hours of the first dose. Within the first 30 days, 5.4 percent of patients in the placebo group and 4.3 percent of patients in the active group had a heart attack, stroke or death. This meant that clopidogrel users had a 21 percent reduction in major events. After 30 days, 6.3 percent of those in the placebo group suffered a major event versus 5.2 percent in the clopidogrel group—an 18 percent difference.

“It is important to note the apparent universality of these results,” Mehta says. “The benefit of combined aspirin and clopidogrel therapy was observed against a broad range of clinical practices in multiple countries.”

Patients on clopidogrel had no significant excess in life-threatening bleeds; however, there was an excess of non-life-threatening bleeds, according to the study. The researchers write that benefits of the drug far outweighed the risk of bleeding.

Mehta says the study’s results can change the practice of medicine in important ways. “Clopidogrel gives cardiologists a new alternative for use in this group of patients to improve outcomes.”

Mehta’s results support the American Heart Association/American College of Cardiology guidelines for managing acute coronary syndromes, which recommend the short-term use of clopidogrel, and suggest that longer-term use may be beneficial.

“Both aspirin and clopidogrel should be initiated early and continued long term, with other medications as appropriate,” Mehta says. “The continued use of these treatments will lead to the greatest benefits in the largest number of patients.”

Co-authors are: Salilm Yusuf, MBBS; Feng Zhao, M.Sc.; Bernard Gerh, M.B., Ch.B.; Patrick Commerford, M.B., Ch.B.; Mel Blumenthal, M.D.; Andrzej Budaj, M.D.; Thomas Wittlinger, Dr. Med.; and Keith A.A. Fox, M.D., Ch.B.

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