Cangrelor for ST-Segment–Elevation Myocardial Infarction: Pharmocodynamic Evidence Is In

Abstract

Cangrelor is an intravenous P2Y12-receptor antagonist indicated for use in patients undergoing percutaneous coronary intervention (PCI), in conjunction with acetylsalicylic acid, to reduce thrombotic adverse events, in patients who have not received oral P2Y12 inhibitors before PCI or where oral P2Y12 inhibition is not feasible or desirable. In comparison with oral P2Y12 inhibition, cangrelor has the pharmacokinetic advantages of adequate platelet inhibition within minutes of administration and a half-life of 3 to 6 minutes with a return of complete platelet function within 60 minutes of discontinuation.1 The pivotal 3 randomized clinical trials of the CHAMPION trial program (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition)2–4 were pooled in an analysis showing that cangrelor treatment in comparison with clopidogrel reduced periprocedural ischemic complications but increased the risk of mild bleeding.5 Patients with ST-segment–elevation myocardial infarction (STEMI) only constituted ≈12% of the study population in CHAMPION, but with a consistent 19% relative reduction of the primary end point. From a clinical perspective, the STEMI population is ideal for cangrelor because there is little time for pretreatment with oral P2Y12 inhibitors and increased thrombotic risk. Furthermore, pretreatment is questionable before angiographic diagnosis if the patient needs acute surgery. In a large registry study we did not find any benefit from pretreatment with ticagrelor before arriving at the PCI laboratory.6 In contrast to the study populations in CHAMPION, current real-world use of cangrelor in Sweden was recently reported to be almost exclusively in patients with STEMI (>98%).7 Furthermore, in CHAMPION, cangrelor was combined with clopidogrel, which is now replaced in the guidelines by the more potent P2Y12 inhibitors ticagrelor and prasugrel for acute coronary syndromes. Thus, there is an urgent need for clinical information on the use of cangrelor in combination with ticagrelor for patients who have STEMI treated with primary PCI (P-PCI). The CANTIC study (Platelet Inhibition with Cangrelor and Crushed TICagrelor in STEMI Patients Undergoing Primary Percutaneous Coronary Intervention) is a prospective, randomized, double-blind, placebo-controlled, parallel design investigation of the pharmacodynamic effects of cangrelor versus placebo in patients undergoing P-PCI treated with crushed ticagrelor presented in this issue of Circulation.8 After diagnostic angiography, patients were randomly assigned to a blinded 2-hour infusion of either cangrelor or placebo. At the same time, 180 mg of crushed ticagrelor was administered to both groups. Planned use of glycoprotein IIb/IIIa inhibitors (GPI) was not allowed. Platelet reactivity was measured with VerifyNow P2Y12 point-of-care testing and vasodilator-stimulated phosphoprotein. © 2019 American Heart Association, Inc.