Clopidogrel for Reduction of Events During Observation - CREDO


This trial compared pretreatment compared with no pretreatment with clopidogrel prior to elective PCI


Pretreatment with clopidogrel prior to PCI will result in a reduction in death, MI, or urgent TVR at 28 days

Study Design

Study Design:

Patients Enrolled: 2,116
Mean Follow Up: 1 year
Female: 28

Patient Populations:

Symptomatic coronary artery disease with objective evidence of ischemia referred for elective or urgent PCI


Child bearing potential, active internal bleeding or hemorrhagic diathesis, acute Q wave myocardial infarction within 24 hours

Drug/Procedures Used:

Patients were treated 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 were not pre-treated discontinued clopidogrel but were maintained on aspirin, for a total treatment time of 1 year.

Concomitant Medications:

GP IIb/IIIa inhibitors at the discretion of the investigator. 20% of patients were treated with GP IIb/IIIa inhibitors, predominantly abciximab.

Principal Findings:

Clopidogrel-pretreated patients showed a nonsignificant 18.5% relative reduction in the primary end point of death/MI/urgent TVR by 28 days (6.8% vs 8.3%, p=0.23). Likewise, in a subgroup analysis looking at patients pretreated for <6 hours, there was no difference in the primary endpoint (7.9% vs 7.0%, p=0.56). However, in patients pretreated for 6-24 hours, death/MI/urgent TVR was lower in the pretreatment group compared with no pretreatment (5.8% vs 9.4%, p=0.05). Major bleeding did not differ between the pretreatment and no pretreatment arms regardless of the use of adjunct GP IIb/IIIa inhibitors (2.1% for pretreatment vs 2.3% for no pretreatment with use of GP IIb/IIIa inhibitor, p=NS; 2.3% for pretreatment vs 1.3% for no pretreatment without use of GP IIb/IIIa inhibitor, p=NS).


The CREDO trial demonstrated that administration of a loading dose of clopidogrel before elective PCI in addition to standard aspirin was not associated with a reduction in events in the overall cohort. While the event rate was slightly higher among patients treated with clopidogrel for less than 6 hours before the PCI (7.9% vs 7.0%), the event rate was lower (5.8% vs 9.4%, p=0.05) if pretreatment lasted for more than 6 hours. There is currently no recommended clopidogrel pretreatment duration for use at the time of elective PCI. The related PCI-CURE study, a substudy of 2,658 patients from the CURE trial who underwent PCI at the discretion of the physician, showed a 36% relative risk reduction in 30 day cardiac death, MI and urgent TVR with pretreatment use of clopidogrel (p=0.03). The PCI-CURE study differs from the CREDO trial in that pretreatment lasted a median of 10 days in PCI-CURE and patients were mostly from outside the US; the CREDO trial was conducted at US centers only. Additionally, CURE patients had acute coronary syndromes and those in CREDO were undergoing elective PCI. The combination of clopidogrel and GP IIb/IIIa was not associated with a higher rate of major bleeding events. Specific cardiac event rates by use of GP IIb/IIIa were not reported at this time. Long term outcomes have not yet been reported.


JAMA 2002 Nov 288:2411-20. Presented at TCT 2002, late breaking clinical trials

Keywords: Risk, Coronary Artery Disease, Acute Coronary Syndrome, Platelet Aggregation Inhibitors, Pyridinolcarbamate, Ticlopidine, Hemorrhage, Purinergic P2Y Receptor Antagonists, Platelet Membrane Glycoprotein IIb, Platelet Glycoprotein GPIIb-IIIa Complex

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