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
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