Platelet Inhibition With Cangrelor and Crushed Ticagrelor in Patients With ST-Segment–Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Abstract

Background: The platelet inhibitory effects induced by oral P2Y 12 receptor antagonists are delayed in patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention (P-PCI). In turn, this leads to a gap in platelet inhibition, exposing patients to an increased risk of early thrombotic complications and underscoring the need to define strategies associated with more effective platelet inhibition in the peri–primary percutaneous coronary intervention period. Cangrelor is an intravenous P2Y 12 inhibitor with prompt and potent antiplatelet effects. However, to date, there are limited data on the effects of cangrelor used in combination with ticagrelor in patients undergoing primary percutaneous coronary intervention. Moreover, questions have emerged on the potential for drug–drug interactions during the transition from cangrelor to oral P2Y 12 inhibitors. Methods: This was a prospective, randomized, double-blind, placebo-controlled pharmacodynamic study conducted in patients undergoing primary percutaneous coronary intervention (n=50) who were randomized to treatment with either cangrelor or matching placebo (bolus followed by 2-hour infusion). All patients received ticagrelor 180-mg loading dose administered as crushed tablets at the time of cangrelor/placebo bolus administration. Pharmacodynamic analyses were performed at 8 time points. Pharmacodynamic effects were measured as P2Y 12 reaction units by VerifyNow and platelet reactivity index by vasodilator-stimulated phosphoprotein. Results: Compared with placebo, cangrelor was associated with reduced P2Y 12 reaction units as early as 5 minutes after bolus, which persisted during the entire duration of drug infusion, including at 30 minutes (63 [32–93] versus 214 [183–245]; mean difference, 152 [95% CI, 108–195]; P <0·001; primary end point). Parallel findings were shown with platelet reactivity index. Accordingly, high on-treatment platelet reactivity rates were reduced with cangrelor. After discontinuation of cangrelor/placebo infusion, there were no differences in levels of platelet reactivity between groups, ruling out a drug–drug interaction when cangrelor and ticagrelor are concomitantly administered. Conclusions: In patients undergoing primary percutaneous coronary intervention, cangrelor is an effective strategy to bridge the gap in platelet inhibition associated with the use of oral P2Y 12 inhibition induced by ticagrelor. Ticagrelor can be administered as a crushed formulation concomitantly with cangrelor without any apparent drug–drug interaction. The clinical implications of these pharmacodynamic findings warrant investigation in an adequately powered clinical trial. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03247738

Prehospital opioid dose and myocardial injury in patients with ST elevation myocardial infarction

“…20 Alternatively, bridging with cangrelor, an intravenous P2Y12 inhibitor may be an effective strategy for tackling delayed bioavailability of oral P2Y12 inhibitors. 21 After adjustment for multiple comorbidities and hospital effect, each 1 mg of morphine equivalent was associated with a 1.4% increase in peak CK; however, this was no longer statistically significant after adjusting for TIMI flow pre-PCI. All model results were included to enable balanced analysis of the results.…”

Platelet-Derived Thrombogenicity Measured by Total Thrombus-Formation Analysis System in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

“…34 Cangrelor has also been expected to improve clinical outcomes. 35 It has been recently reported that cangrelor produces potent PRU-based P2Y12 inhibition even at the time of PPCI, although coronary microvascular function and infarct size are not improved. 36 Moreover, crushed P2Y12 inhibitor tablets may be effective in reducing plateletderived thrombogenicity during PPCI.…”

High Platelet Reactivity after Transition from Cangrelor to Ticagrelor in Hypothermic Cardiac Arrest Survivors with ST-Segment Elevation Myocardial Infarction

“…While a recent meta-analysis comparing different P2Y12 inhibitors in patients undergoing PCI suggests no clinical outcome benefit of cangrelor over oral P2Y12 inhibitors [22], cangrelor may be the appropriate initial P2Y12 inhibitor for hypothermic cardiac arrest survivors with STEMI. Crushed ticagrelor seems to be a reasonable P2Y12 inhibitor for early oral loading in this population, given the solid pharmacodynamic evidence for its safe and effective use in non-cardiac arrest patients receiving cangrelor [23]. Variable P2Y12 inhibitor kinetics in hypothermic cardiac arrest patients may render thienopyridines less suitable in view of their possible pharmacodynamic interactions.…”