Initial experience with an intravenous P2Y12 platelet receptor antagonist in XXXX undergoing percutaneous coronary intervention: results from a 2-part, phase II, multicenter, randomized, placebo- and active-controlled trial.

@entity1 @entity548 @entity857 @entity1423 @entity299 @entity715 @entity37502 @entity204
BACKGROUND: Platelet-initiated acute @entity715 and coronary embolization are fundamental in the pathophysiology of complications during percutaneous coronary intervention (PCI). Cangrelor (formerly @entity37502 ) is a novel, rapidly acting, intravenous, specific antagonist of @entity1423 via binding to the @entity857 ( @entity857 ) P2Y12 receptor subtype. The primary aims of this study were to assess the initial safety and pharmacodynamics of cangrelor in @entity1 undergoing PCI. METHODS: In part 1, @entity1 undergoing PCI were randomized to an 18- to 24-hour of either placebo, 1-, 2-, or 4-microg/kg per minute cangrelor in addition to aspirin and heparin beginning before PCI. In part 2, @entity1 were randomized to receive either cangrelor (4 microg/kg per minute) or abciximab before PCI. The primary end point was the composite incidence of major and @entity548 through 7 days. Secondary end points included the occurrence of major adverse coronary events ( @entity204 , MI, and unplanned repeat coronary intervention) through 30 days plus ex vivo @entity1423 and @entity548 times. RESULTS: Two hundred @entity1 (3 dosage groups and placebo) were studied in part 1, and 199 additional @entity1 were then randomized in the second part, comparing 1 dose of cangrelor and abciximab. Combined major and @entity548 occurred in 13% of those receiving cangrelor and in 8% in those randomized to placebo (P = non significant [NS]) during part 1 and in 7% receiving cangrelor compared with 10% randomized to abciximab (P = NS), during part 2. The 30-day composite incidence of adverse @entity299 was similar between those receiving cangrelor and those receiving abciximab during part 2 (7.6% vs 5.3%, respectively, P = NS). Mean inhibition of ex vivo @entity1423 in response to 3 micromol/L @entity857 at steady state was 100% for both cangrelor 4 microg/kg per minute and abciximab groups in part 2. After termination of infusion, @entity1423 returned to baseline response more rapidly with cangrelor compared with abciximab. There was a trend toward longer @entity548 time prolongation and lower platelet count with abciximab compared with cangrelor. CONCLUSIONS: This initial experience with intravenous cangrelor during PCI suggests an acceptable risk of @entity548 and adverse @entity299 while achieving rapid, reversible @entity1423 via competitive binding to the @entity857 P2Y12 platelet receptor with less prolongation of @entity548 time then the glycoprotein IIb/IIIa receptor antagonist abciximab.
