Pre-PCI clopidogrel shows benefit
A recent study found that pretreatment with the anti-platelet drug clopidogrel (Plavix) before percutaneous coronary intervention (PCI) significantly reduced by 46% the odds of cardiovascular death, recurrent myocardial infarction (MI), or stroke within 30 days following PCI.
Researchers at Brigham and Women’s Hospital and Harvard Medical School in Boston and their colleagues around the world wanted to see if clopidogrel treatment given before PCI had more benefit than clopidogrel treatment started at the time of PCI in preventing major adverse cardiovascular events in patients with recent ST-segment elevation myocardial infarction (STEMI).
The researchers studied 1,863 patients undergoing PCI after mandated angiography in CLARITYThrombolysis in Myocardial Infarction (TIMI) 28, a randomized, double-blind, placebo-controlled trial of clopidogrel in patients receiving fibrinolytics for STEMI. Patients were enrolled in this PCI-CLARITY (Clopidogrel as Adjunctive Reperfusion Therapy) study from February 2003 through October 2004.
Patients received aspirin and were randomized to receive either clopidogrel (300 mg loading dose and then 75 mg once daily) or placebo-initiated with fibrinolysis and then given until the coronary angiography. The angiography was performed two to eight days after initiation of the study drug, at the discretion of the local investigator. It was recommended that open-label clopidogrel (including a loading dose) be administered after the diagnostic angiogram for patients undergoing coronary artery stenting. The primary outcome of the study was the incidence of the composite of cardiovascular death, recurrent MI, or stroke from PCI to 30 days after randomization.
"This [pretreatment] benefit was seen in patients with STEMI treated with fibrinolytics who subsequently underwent PCI on average three days later, but with a consistent benefit regardless of the time from initiation of pretreatment to PCI," the researchers say. "Moreover, benefits were seen regardless of whether patients received a GpIIb/ IIIa inhibitor at the time of PCI or whether patients received a loading dose of open-label clopidogrel at the time of PCI." They also found no significant excess in TIMI major or minor bleeding.
PCI-CLARITY has implications for clinical practice, the researchers write. "For every 100 patients undergoing PCI in whom a strategy of clopidogrel pretreatment is adopted, approximately two MIs would be prevented before PCI and an additional two cardiovascular deaths, MIs, or strokes would be prevented after PCI to 30 days. Overall, only 23 patients would need to be pretreated with clopidogrel to prevent one cardiovascular death, MI, or stroke. This benefit with pretreatment is achieved when compared with the current practice in which patients receive a loading dose of clopidogrel at the time of PCI and a maintenance dose thereafter. Thus in 100 patients, four major cardiovascular events can be avoided simply by the use of one to three doses of clopidogrel before PCI."
PCI-CLARITY, taken with the results of the PCI-CURE (PCI-Clopidogrel in Unstable angina to prevent Recurrent Events) and CREDO (Clopidogrel for the Reduction of Events During Observation) studies, demonstrates a "clear and consistent benefit with clopidogrel pretreatment for PCI," the researchers say. "The significant reduction in adverse cardiovascular events before PCI suggests that a strategy of clopidogrel pretreatment should be initiated as soon as possible. Accordingly, even if clopidogrel is not given at presentation, once the decision is made to proceed with angiography, and hence possible PCI, initiation of pretreatment will maximize the benefit."
However, PCI-CLARITY has several limitations, such as PCI not being randomized, say David J. Moliterno, MD, professor and chief of cardiovascular medicine, and Steven R. Steinhubl, MD, associate professor of internal medicine, at the University of Kentucky in Lexington. They published their comments in an editorial accompanying the study results.
Despite this, the study provides important data, the editorialists say, and application of the study findings seems straightforward — patients receiving thrombolytic therapy for ST-segment elevation myocardial infarction should also receive a 300 mg loading dose of clopidogrel followed by 75 mg daily. In addition, they say, clinicians should consider giving 600 mg clopidogrel as a loading dose, "even though this approach has not been formally tested with thrombolytic therapy."
"So far, no major safety concerns have emerged with 600- or 900-mg loading doses," the editorialists say. "Finally, all patients not receiving a loading dose within several days of angiography should be considered for clopidogrel retreatment (i.e., repeat loading dose) at the time of PCI."
The article was published on-line on Sept. 4 on the web site of the Journal of the American Medical Association and in the Sept. 14 issue of the journal.
A recent study found that pretreatment with the anti-platelet drug clopidogrel (Plavix) before percutaneous coronary intervention (PCI) significantly reduced by 46% the odds of cardiovascular death, recurrent myocardial infarction (MI), or stroke within 30 days following PCI.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content