Effect of Clopidogrel in Acute Coronary Syndromes: The Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) Trial
Salim Yusuf
McMaster University, Hamilton, Canada

Despite current availability of several treatments, patients with acute coronary syndromes have high rates of major cardiovascular events. The results of the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) Trial clearly demonstrate a reduction in myocardial infarction, stroke, and death in patients with acute coronary syndromes who received clopidogrel therapy.

Patients with acute coronary syndromes, or unstable angina, are at very high risk for adverse cardiac events including myocardial infarction, stroke, and death. This high risk for considerable morbidity and mortality exists despite the availability of anti-clotting therapies such as aspirin. Because acute thrombosis is an important pathophysiologic component in the development of complications of unstable angina, investigation of anti-thrombotic therapies remains an important area of clinical research. The investigators conducting the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) Trial randomized 12,562 patients within 24 hours of onset of acute coronary syndromes to receive aspirin plus either clopidogrel 300 mg (immediately followed by clopidogrel 75 mg once daily) or placebo. Patients were followed for a mean of 9 months.

The results of this study are quite dramatic: They demonstrate significant reductions in all primary and secondary outcomes in patients receiving clopidogrel therapy compared with those receiving placebo. The primary combined outcome of death, myocardial infarction, or stroke occurred in 9.3% of clopidogrel patients versus 11.5% of placebo patients (relative risk = 0.80; p<.00005). The primary combined outcome plus refractory ischemia occurred in 16.7% of clopidogrel patients and 19.0% of placebo patients (relative risk = 0.86; p <.005). Dr. Yusuf commented: "Interestingly, the survival curves for the placebo and clopidogrel groups began to diverge almost immediately -- in fact, within about 2 hours after initiation of therapy!" The survival curves continued to diverge throughout the follow-up period, demonstrating an early significant difference that was consistent over time. Safety data were also impressive, with only 3 transfusions and 3 major bleeds per 1,000 patients treated with clopidogrel. There was no significant excess in life-threatening bleeds or hemorrhagic strokes in the clopidogrel group compared with the results for the placebo group.

Dr. Yusuf concluded: "This translates into 22 fewer cases of myocardial infarction, stroke, or death per 1,000 patients treated with clopidogrel, and 28 per 1,000 fewer instances of all cardiovascular events. Safety was excellent, with 3 transfusions and 3 major bleeds per 1,000 treated patients, and with no incremental cases of life-threatening bleeding or hemorrhagic stroke. There are about 1.5 million myocardial infarctions per year in the United States, of which about one third of patients die, one third have Q-wave infarctions, and one third have non-Q-wave infarctions. Therefore, about 500,000 people each year in the United States alone fall into the category of having unstable angina or non-Q-wave infarction. Based on the results of this trial, we can project that if they all received clopidogrel therapy, we would save approximately 50,000 to 100,000 cases of myocardial infarction, stroke, and death each year in the United States alone, and hundreds of thousands more worldwide, with a very small incremental incidence of major bleeds or transfusions. Weユre very excited about these results, and we hope they are accepted and applied by all of our colleagues who treat patients with these very common cardiovascular problems."

Reporter: Andre Weinberger, MD


Copyright 2000-2013 by HESCO International, Ltd. All rights reserved.