EFFECTS
OF CLOPIDOGREL IN ADDITION TO ASPIRIN IN PATIENTS WITH ACUTE CORONARY SYNDROMES
WITHOUT ST-SEGMENT ELEVATION
Yusuf
S, et al; The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators.
N Engl J Med 2001 Aug 16;345(7):494-502.
BACKGROUND:
Despite current treatments, patients who have acute coronary syndromes without
ST-segment elevation have high rates of major vascular events. We evaluated the
efficacy and safety of the antiplatelet agent clopidogrel when given with
aspirin in such patients.
METHODS:
We randomly assigned 12,562 patients who had presented within 24 hours after
the onset of symptoms to receive clopidogrel (300 mg immediately, followed by
75 mg once daily) (6259 patients) or placebo (6303 patients) in addition to
aspirin for 3 to 12 months.
RESULTS:
The first primary outcome--a composite of death from cardiovascular causes,
nonfatal myocardial infarction, or stroke--occurred in 9.3 percent of the
patients in the clopidogrel group and 11.4 percent of the patients in the
placebo group (relative risk with clopidogrel as compared with placebo, 0.80;
95 percent confidence interval, 0.72 to 0.90; P<0.001). The second primary
outcome--the first primary outcome or refractory ischemia--occurred in 16.5
percent of the patients in the clopidogrel group and 18.8 percent of the
patients in the placebo group (relative risk, 0.86; 95 percent confidence
interval, 0.79 to 0.94; P<0.001). The percentages of patients with in-hospital
refractory or severe ischemia, heart failure, and revascularization procedures
were also significantly lower with clopidogrel. There were significantly more
patients with major bleeding in the clopidogrel group than in the placebo group
(3.7 percent vs. 2.7 percent; relative risk, 1.38; P=0.001), but there were not
significantly more patients with episodes of life-threatening bleeding (2.2
percent [corrected] vs. 1.8 percent; P=0.13) or hemorrhagic strokes (0.1
percent vs. 0.1 percent).
CONCLUSIONS:
The antiplatelet agent clopidogrel has beneficial effects in patients with
acute coronary syndromes without ST-segment elevation. However, the risk of
major bleeding is increased among patients treated with clopidogrel.
COMMENTS:
The patients included in this study all had significant signs of ischemia, ie.
ST depression, T wave inversion, or elevated Troponin. Patients with suspicion
for ACS without objective findings, ie. a good history but nonspecific EKGs and
normal enzymes, may not benefit but are exposed to the higher bleeding
complications.