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Cangrelor during Percutaneous Coronary Intervention - Cangrelor during PCI
Description:
The goal of the trial was to evaluate treatment with the novel platelet aggregation antagonist cangrelor among patients undergoing percutaneous coronary intervention (PCI).
Study Design
Study Design:
Patients Enrolled: 399
Mean Follow Up: 30 days
Mean Patient Age: Mean age 62 years
Patient Populations:
Age 18-80 years, ≥1 coronary lesion with >60% stenosis undergoing either elective or urgent PCI with or without intracoronary stent implantation
Exclusions:
ST-segment elevation acute myocardial infarction (MI), fibrinolytic therapy within 48 hours, class III to IV heart failure, hypotension, cardiogenic shock, prior stent placement in the area of the target lesion, uncontrolled hypertension, ischemic stroke within 30 days, or any evidence of recent major bleeding.
Primary Endpoints:
Composite of major and minor bleeding through 7 days
Secondary Endpoints:
Major adverse coronary events (death, MI, or unplanned repeat coronary intervention) by 30 days, ex vivo platelet aggregation and bleeding times.
Drug/Procedures Used:
The trial was conducted in two parts. In part 1, the dose finding part, patients were randomized prior to PCI in a double-blind manner to cangrelor (1, 2 or 4 µg/kg/min; n=147) or placebo (n=50) treatment for 18-24 hours. In part 2, patients were randomized open-label prior to PCI to cangrelor (4 µg/kg/min; n=105) or abciximab (n=94).
Concomitant Medications:
Aspirin and heparin
Principal Findings:
Mean duration of treatment was 18.3 to 21.1 hours with cangrelor. In part 1, there was no difference in the primary composite endpoint of major or minor bleeding by 7 days for cangrelor vs placebo (13% vs 8%, p=NS), with some of evidence of a dose escalation effect (8% for lowest dose, 12% for intermediate dose, and 19% for highest dose). In part 2, there was also no difference in the primary composite of major or minor bleeding by 7 days for cangrelor vs abciximab (7% vs 10%, p=NS).
MACE at 30 days occurred in 10% of the cangrelor low dose group, 17% of the intermediate dose group, and 19% of the high dose group compared with 12% of the placebo group. MACE at 30 days did not differ for cangrelor vs abciximab (7.6% vs 5.3%, p=NS). In the cangrelor groups, platelet inhibition was maximal by 15 minutes after drug infusion, returning to normal within 15 minutes of study drug discontinuation in all groups except the 4 µg/kg/min group. Mean percentage inhibition of platelet aggregation prior to infusion end ranged from 87%-100% with cangrelor. Bleeding times trended shorter with cangrelor compared with abciximab.
Interpretation:
Among patients undergoing PCI, treatment with the novel platelet aggregation antagonist cangrelor was not associated with increased major or minor bleeding by 7 days compared with placebo or compared with abciximab.
Cangrelor inhibits platelet aggregation via competitive binding to the ADP P2Y12 platelet receptor. Clopidogrel, which also inhibits platelet aggregation via the ADP P2Y12 platelet receptor pathway, has previously been shown in many trials to reduce thrombotic complications following stent placement. In the present trial, cangrelor was given intravenously for a relatively short time, unlike oral clopidogrel which is a long term medication following stent placement. Larger trials with cangrelor are warranted given the safety profile and its ability to rapidly but reversibly inhibition of platelet aggregation.
References:
Greenbaum AB, et al. Initial experience with an intravenous P2Y12 platelet receptor antagonist in patients undergoing percutaneous coronary intervention: Results from a 2-part, phase II, multicenter, randomized, placebo- and active-controlled trial. Am Heart J 2006;151:689.e12689.e10.
Keywords: Bleeding Time, Platelet Aggregation Inhibitors, Platelet Aggregation, Coronary Disease, Ticlopidine, Constriction, Pathologic, Immunoglobulin Fab Fragments, Stents, Percutaneous Coronary Intervention
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