New Therapy Identified for Patients who Experience a Heart Attack
Results from international clinical trial provide evidence that clopidogrel helps open cblocked arteries and decreases the odds of a second heart attack by 31 percent
Boston, MA – Patients who experience a severe heart attack are frequently treated with a fibrinolytic (clot-buster), heparin (anticoagulant) and aspirin (antiplatelet medication) to dissolve the clot that is blocking the coronary artery and reduce morbidity and mortality associated with the event. However, even after this therapy, 20 to 25 percent of patients still have a blocked artery, putting them at continued risk of death. To address this issue, researchers from Brigham and Women’s Hospital (BWH) led the CLARITY-TIMI 28 trial and found that the addition of a second antiplatelet medication – clopidogrel (Plavix) – can help keep the artery open and reduce second heart attacks. These results indicate that clopidogrel can now be added to the current treatment regimen to reduce heart attack-related damage among patients coming to the hospital with heart attacks.
Results are being presented by Marc S. Sabatine, MD, MPH, an associate physician in the Cardiovascular Division at BWH and an instructor in Medicine at Harvard Medical School (HMS) at the American College of Cardiology (ACC) 54th Annual Scientific Session in Orlando, Florida. The results will also be published simultaneously in the New England Journal of Medicine online on March 9, 2005, and then in print in the March 24, 2005 issue.
“We have demonstrated that the addition of clopidogrel to standard therapy in patients experiencing an acute myocardial infarction significantly increases the odds of having and maintaining an open coronary artery,” Sabatine stated. “Clopidogrel offers an effective, simple, inexpensive and safe means by which to improve reperfusion and prevent further damage to the heart in these high-risk patients.”
Heart attacks affect 10 million patients worldwide each year, of whom four million have severe attacks due to a completely blocked coronary artery that requires clot-busting medication or emergent angioplasty. Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY) – Thrombolysis in Myocardial Infarction (TIMI) 28, a multi-national, randomized, double-blind, placebo-controlled trial, found that adding clopidogrel reduced the odds of having a blocked coronary artery, dying or having a second heart attack by 36 percent. With this treatment, nearly 90 percent of patients had open arteries.
The trial included 3,491 men and women, 75 years or younger, at 319 sites in 23 countries. The primary endpoint of the trial was a composite of an occluded (clogged) infarct-related artery or death or second heart attack prior to coronary angiography. All patients in the trial experienced the onset of their heart attack within the 12 hours preceding treatment and received standard clot-busting treatment and aspirin to open the clogged artery. They then received either clopidogrel (300 mg loading dose, then 75 mg once daily) or placebo up to the time of angiography. Clopidogrel’s benefits in opening arteries were consistent across a broad range of patient subgroups, including gender and the different types of fibrinolytics and heparins commonly used in practice. Additionally, during the 30-day follow-up period, the benefits of clopidogrel treatment were maintained. A 31 percent reduction in the odds of a recurrent heart attack and a 20 percent reduction in the odds of the composite of death from cardiovascular causes, recurrent heart attack or need for urgent coronary revascularization were observed.
The rate of major bleeding in the clopidogrel group was 1.3 percent, similar to the 1.1 percent in the placebo group. The additional of clopidogrel did not increase the risk of intracranial hemorrhage, a rare but dreaded complication of fibrinolytic therapy and a limiting factor in prior attempts to improve reperfusion therapy.
“Patients with acute myocardial infarction have the highest rate of morbidity and mortality of all patients suffering from atherothrombotic coronary artery disease. Despite treatment with standard fibrinolytic regimens, many patients still have a blocked artery, putting them at double the risk of death,” said senior author BWH’s Eugene Braunwald, MD, HMS Distinguished Hersey Professor of Medicine and chairman of the TIMI Group. “The results of the CLARITY-TIMI 28 trial constitute a significant step forward in MI management.”
Supporting these BWH-led results, at the ACC annual meeting, separate research from the COMMIT trial, involving 46,000 patients, demonstrated a clear survival benefit with the use of clopidogrel in patients with acute myocardial infarction.
“These new studies build on prior trials to show that clopidogrel therapy can benefit essentially all types of patients coming to the hospital including those who have experienced an acute heart attack,” stated study principal investigator Christopher P. Cannon, MD of BWH and associate professor of Medicine at HMS. “The addition of clopidogrel marks the first addition to fibrinolytic regimens in more than a decade that improves outcomes and mortality for heart attack patients.”
The CLARITY-TIMI 28 trial was supported by a grant from Sanofi-Aventis and Bristol-Myers Squibb.
Please contact BWH Media Relations for more information at (617) 534-1600 or BWHMediaRelations@partners.org.
BWH is a 747-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare System, an integrated health care delivery network. BWH is committed to excellence in patient care with expertise in virtually every specialty of medicine and surgery. The BWH medical preeminence dates back to 1832 and today that rich history in clinical care is coupled with its national leadership in quality improvement and patient safety initiatives, dedication to educating and training health care professionals, and strength in biomedical research. With $370M in funding and more than 500 research scientists, BWH is an acclaimed leader in clinical, basic and epidemiological investigation - including the landmark Nurses Health Study, Physicians Health Studies, and the Women's Health Initiative. For more information visit www.brighamandwomens.org
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