CLINICAL RESEARCH: INTERVENTIONAL CARDIOLOGY
Optimal Timing for the Initiation of Pre-Treatment With 300 mg Clopidogrel Before Percutaneous Coronary Intervention
Steven R. Steinhubl, MD*,*,
Peter B. Berger, MD ,
Danielle M. Brennan, MS ,
Eric J. Topol, MD for the CREDO Investigators
* Linda and Jack Gill Heart Institute, University of Kentucky, Lexington, Kentucky
Duke Clinical Research Institute, Duke University, Durham, North Carolina
Cleveland Clinic Foundation, Duke University, Durham, North Carolina
Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio
Manuscript received March 28, 2005;
revised manuscript received October 4, 2005,
accepted October 10, 2005.
* Reprint requests and correspondence: Dr. Steven R. Steinhubl, Division of Cardiovascular Medicine, 900 South Limestone, 326 Charles T. Wethington Building, Lexington, Kentucky 40536-0200. (Email: Steinhubl{at}uky.edu).
OBJECTIVES: This study sought to determine the optimal timing of a 300-mg clopidogrel loading dose before percutaneous coronary intervention (PCI) in patients enrolled in the Clopidogrel for the Reduction of Events During Observation (CREDO) trial.
BACKGROUND: A loading dose of clopidogrel before a PCI has become relatively commonplace, although the data supporting this practice are limited and sometimes conflicting.
METHODS: Patients were randomized to receive either 300 mg clopidogrel or a matching placebo administered a minimum of 3 h and a maximum of 24 h before PCI. The primary 28-day combined end point was death, myocardial infarction, or urgent target vessel revascularization. Linear splines were used to summarize the effect of the time of pre-treatment as a continuous variable.
RESULTS: A total of 1,762 patients were evaluated. For patients randomized to placebo, there was no relationship between the duration of pre-treatment and the occurrence of the primary end point, whereas longer durations of pre-treatment in patients randomized to clopidogrel were associated with improved outcomes. The event rates diverged maximally at 24 h. The difference in outcomes between placebo and clopidogrel pre-treated patients was not significant until  15 h pre-treatment, with a 58.8% (p = 0.028) reduction in the primary end point in patients pre-treated with clopidogrel 15 h compared with placebo.
CONCLUSIONS: When a 300-mg loading dose of clopidogrel is used, little benefit is obtained compared with just 75 mg at the time of the PCI when the treatment duration is <12 h. In patients pre-treated for longer durations, the optimal duration seems to approach 24 h.
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Abbreviations and Acronyms
| | GP = glycoprotein | | MI = myocardial infarction | | PCI = percutaneous coronary intervention | | UTVR = urgent target vessel revascularization |
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