The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators: Effects of Clopidogrel in Addition to Aspirin in Patients With Acute Coronary Syndromes Without ST-Segment Elevation - CURE

Description:

In the Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial (CURE), investigators evaluated the effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes (ACSs) without ST-segment elevation.

Hypothesis:

Is clopidogrel (an antiplatelet agent), on the background of aspirin therapy, effective and safe in the management of patients with non-ST elevation ACSs?

Study Design

Patients Enrolled: 12,562

Primary Endpoints:

The composite of death from cardiovascular causes, nonfatal MI, or stroke

Drug/Procedures Used:

Patients presenting within 24 hours after the onset of symptoms suggestive of ACSs (n=12,562) were randomized to receive clopidogrel (300 mg immediately, followed by 75 mg once daily; 6,259 patients) or placebo (6,303 patients) in addition to aspirin for 3-12 months.

Principal Findings:

The composite of death from cardiovascular causes, nonfatal myocardial infarction (MI), or stroke (first primary outcome) was significantly lower in the clopidogrel group compared to placebo (9.3% vs. 11.4%, relative risk [RR] 0.80, 95% confidence interval [CI] 0.72-0.90, p<0.001). Similarly, the combined endpoints of the first primary outcome or refractory ischemia (second primary endpoint) was lower in the clopidogrel group (16.5% vs. 18.8%, RR 0.86, 95% CI 0.79-0.94, 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. This benefit in the treatment arm occurred at the expense of more patients with major bleeding in the clopidogrel group than in the placebo group (3.7% vs. 2.7%, RR 1.38, 95% CI 1.13-1.67, p=0.001). Episodes of life-threatening bleeding were similar in the two groups of patients (2.1% vs. 1.8%, RR 1.21; 95% CI 0.95-1.56; p=0.13), as were hemorrhagic strokes (0.1% in both groups).

The antiplatelet agent clopidogrel, when added to aspirin, has beneficial effects in patients with ACSs without ST-segment elevation, as compared to patients taking aspirin alone. However, the risk of major bleeding is increased among patients treated with clopidogrel.

Interpretation:

In this international trial, the majority of people did not undergo percutaneous coronary intervention (PCI). Among the subset of patients treated with PCI, the results of PCI-CURE, published in Lancet 2001;358:527-33, suggest that pretreatment with clopidogrel may be beneficial when administered prior to PCI.

As most patients in CURE were treated conservatively, it remains to be seen how the routine treatment with clopidogrel in all ACS patients impacts the bleeding rate in the United States, where the trend is for a more aggressive, invasive approach to ACS, including coronary artery bypass surgery.

This study suggests a need for further studies to access the risk/benefits of using this agent versus glycoprotein IIb/IIIa inhibitors in the pre- and post-intervention phase. Finally, the cost-effectiveness of this therapy remains to be determined.

References:

Yusuf S, Zhao F, Mehta SR, et al., for the Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494-502.

Clinical Topics: Acute Coronary Syndromes, Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Aortic Surgery, Cardiac Surgery and Heart Failure, Acute Heart Failure, Interventions and ACS

Keywords: Risk, Myocardial Infarction, Stroke, Acute Coronary Syndrome, Platelet Aggregation Inhibitors, Ticlopidine, Purinergic P2Y Receptor Antagonists, Percutaneous Coronary Intervention, Research Personnel, Heart Failure, Confidence Intervals, Coronary Artery Bypass


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