Efficacy and safety of clopidogrel pretreatment before percutaneous coronary intervention with and without glycoprotein IIb/IIIa inhibitor use

Marc S. Sabatine, Hussam N. Hamdalla, Shamir R. Mehta, Keith A. A. Fox, Eric J. Topol, Steven R. Steinhubl, Christopher P. Cannon

Research output: Contribution to journalArticlepeer-review

Abstract

Background

Clopidogrel pretreatment before percutaneous coronary intervention (PCI) has been shown to reduce the risk of death and ischemic complications after PCI. However, the need for clopidogrel pretreatment is debated in patients receiving a glycoprotein IIb/IIIa inhibitor (GPI).
MethodsWe performed a collaborative meta-analysis of the results of 3 randomized trials of clopidogrel pretreatment: PCI-CURE, CREDO, and PCI-CLARITY. Patients were stratified based on GPI use at the time of PCI (a postrandomization subgroup analysis). Odds ratios (ORs) and 95% CIs for the effect of clopidogrel pretreatment versus placebo pretreatment on the incidence of cardiovascular death, myocardial infarction (MI), or stroke for up to 30 days after PCI were calculated for each trial within each GPI stratum and were combined using a random effects model.
ResultsSix thousand three hundred twenty-five patients were included, 32.4% of whom received a GPI. There was a consistent benefit of clopidogrel pretreatment in reducing the incidence of cardiovascular death, MI, or stroke after PCI both in patients who did not receive a GPI (OR 0.72, 95% CI 0.53-0.98, P = .03) and in those who did (OR 0.69, 95% CI 0.47-1.00, P = .05). There was no evidence of heterogeneity in the benefit of clopidogrel pretreatment between GPI use strata (P = .85 for heterogeneity). Clopidogrel pretreatment was not associated with a significant excess of TIMI major or minor bleeding, either in those who did not receive a GPI (OR 1.20, 95% CI 0.76-1.92) or in those who did (OR 1.22, 95% CI 0.71-2.09) (P = .97 for heterogeneity).
ConclusionClopidogrel pretreatment before PCI is beneficial and safe regardless of whether a GPI is used at the time of PCI.

Dual antiplatelet therapy after percutaneous coronary intervention (PCI), using a combination of a P2Y12 adenosine diphosphate (ADP) receptor blocker (such as ticlopidine or clopidogrel) and aspirin, reduces platelet activation and thrombotic and ischemic complications.1 We have previously shown that pretreatment with clopidogrel before PCI significantly reduces cardiovascular death and ischemic complications after PCI. [2], [3] and [4] Accordingly, the most recent PCI guidelines from the American Heart Association (AHA), the American College of Cardiology (ACC), the Society for Cardiovascular Angiography and Intervention (SCAI), and the European Society of Cardiology (ESC) make clopidogrel pretreatment (300 mg at least 6 hours before PCI) a class I recommendation. [5] and [6]

However, the need for clopidogrel pretreatment has been debated in patients receiving a glycoprotein IIb/IIIa inhibitor (GPI) during PCI. Glycoprotein IIb/IIIa inhibitors rapidly achieve near complete inhibition of platelet aggregation, and their use during PCI is recommended in both the AHA/ACC/SCAI and the ESC guidelines.[5] and [6] To that end, more than 80% of patients undergoing PCI in the CRUSADE registry received a GPI.7Although studies have shown the benefit of adding a GPI to clopidogrel in high-risk patients undergoing PCI,8the converse, namely, whether clopidogrel pretreatment before PCI would be beneficial if a patient was ultimately going to receive GPI during PCI, remains unknown. Furthermore, both drugs have been associated with increased rates of bleeding, and thus, the safety of clopidogrel pretreatment in the setting of GPI has been an area of concern.

We therefore performed a collaborative meta-analysis of the effects of clopidogrel pretreatment across 3 trials, PCI-CURE, CREDO, and PCI-CLARITY, in which clopidogrel versus placebo pretreatment was randomly allocated and stratified patients by GPI use.

Original languageEnglish
Pages (from-to)910-917
Number of pages8
JournalAmerican Heart Journal
Volume155
Issue number5
DOIs
Publication statusPublished - May 2008

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