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Clopidogrel for Reduction of Events During Observation - CREDO 1 Year
Description:
CREDO long-term follow-up compared treatment with clopidogrel with no treatment with clopidogrel prior to elective percutaneous coronary intervention (PCI) and though 1 year.
Hypothesis:
Use of pretreatment and long-term clopidogrel following PCI through 1 year will result in reduced death, myocardial infarction (MI), and stroke at 1-year follow-up.
Study Design
Study Design:
Patients Enrolled: 2,116.
Mean Follow Up: 1 year.
Patient Populations:
Likely or planned PCI; symptomatic coronary artery disease with objective evidence of ischemia; age >=21 years.
Exclusions:
Contraindications to antithrombotic/antiplatelet therapy; persistent ST elevation within 24 hours; >50% stenosis of the left main artery; failed coronary intervention in the prior 2 weeks; coronary anatomy not amenable to stent placement; planned staged interventional procedure; administration of: GP IIb/IIIa inhibitor within 7 days, clopidogrel within 10 days, or thrombolytics within 24 hours.
Secondary Endpoints:
Individual components of composite endpoint (death, MI, stroke) at 1 year; death/MI at 1 year; thrombolysis in myocardial infarction (TIMI) major bleed at 1 year; revascularization at 1 year.
Drug/Procedures Used:
Patients were pretreated with either a 300 mg clopidogrel bolus + 325-mg aspirin vs no clopidogrel (placebo) + 325 mg aspirin, 3 to 24 hours before intervention (median 9 hours). At the time of PCI, all patients were started on 75 mg clopidogrel and 325-mg aspirin daily for 28 days. Patients who received active pretreatment continued in a blinded fashion on 75 mg clopidogrel plus aspirin out to 1 year, while the group who was not pretreated discontinued clopidogrel but was maintained on aspirin, for a total treatment time of 1 year.
Concomitant Medications:
Glycoprotein (GP) IIb/IIIa inhibitors at the discretion of the investigator.
Principal Findings:
One-year treatment was completed in 63% of patients in the clopidogrel arm and 61% of patients in the placebo arm (p=NS). The primary endpoint of death, MI or stroke at 1 year was reduced in the clopidogrel arm compared with placebo (8.5% vs 11.5%, 26.9% RRR, p=0.02). None of the individual components of the composite endpoint differed at 1 year (death 1.8% vs 2.4%; MI 6.8% vs 8.7%; stroke 0.9% vs 1.2%; death/MI 8.1% vs 10.7%, p=NS for all comparisons). The rate of major bleed trended higher in the clopidogrel arm (8.8% vs 6.7%, p=0.07). The majority of the major bleeding was CABG-related.
Interpretation:
Use of clopidogrel prior to PCI and up to 1 year along with aspirin was associated with a reduction in the composite endpoint at 1 year. However, there was a trend toward increased major bleeding at 1 year with clopidogrel use, the majority of which was CABG-related. The PCI-CURE trial, which was a substudy of the CURE trial in which patients with acute coronary syndrome (ACS) underwent PCI at the discretion of the investigator, showed a reduction in the long-term composite of cardiac death, MI or target vessel revascularization (TVR) with clopidogrel treatment (p=0.03) and with cardiac death or MI (p=0.047). Patients in the PCI-CURE study received clopidogrel therapy for a mean duration of 9 months. There are several differences between the 2 trials, notably the different 1-year composite endpoint (addition of stroke vs TVR to death and MI), the patient population (ACS in PCI-CURE; elective PCI in CREDO), and a low use of GP IIb/IIIa inhibitors in CURE. The effect of the addition of GP IIb/IIIa inhibitors to the use of clopidogrel for elective PCI was not addressed in the CREDO trial; however, the Intracoronary Stenting and Antithrombotic Regimen Rapid Early Action for Coronary Treatment (ISAR-REACT) trial, in which all patients will receive 600 mg of clopidogrel pre-PCI and will then be randomized to abciximab or placebo, will address this issue.
References:
Presented at AHA 2002, late breaking clinical trials. JAMA. 2002;288:2411-2420.
Keywords: Coronary Artery Disease, Myocardial Infarction, Stroke, Acute Coronary Syndrome, Follow-Up Studies, Platelet Aggregation Inhibitors, Ticlopidine, Immunoglobulin Fab Fragments, Platelet Membrane Glycoprotein IIb, Purinergic P2Y Receptor Antagonists, Percutaneous Coronary Intervention, Research Personnel, Platelet Glycoprotein GPIIb-IIIa Complex
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