Cangrelor versus Ticagrelor in Patients Treated with Primary Percutaneous Coronary Intervention: Impact on Platelet Activity, Myocardial Microvascular Function and Infarct Size: A Randomized Controlled Trial

Abstract

Background Oral P2Y12 inhibitors take more than 2 hours to achieve full effect in healthy subjects and this action is further delayed in patients with acute myocardial infarction. Intravenous P2Y12 inhibition might lead to more timely and potent anti-platelet effect in the context of emergency primary angioplasty, improving myocardial recovery. Objectives This article compares the efficacy of intravenous cangrelor versus ticagrelor in a ST-elevation myocardial infarction (STEMI) population treated with primary percutaneous coronary intervention (PPCI). Materials and Methods In an open-label, prospective, randomized controlled trial, 100 subjects with STEMI were assigned 1:1 to intravenous cangrelor or oral ticagrelor. The co-primary endpoints were platelet P2Y12 inhibition at infarct vessel balloon inflation time, 4 and 24 hours. Secondary endpoints included indices of coronary microcirculatory function: index of microvascular resistance (IMR), initial infarct size (troponin at 24 hours) and final infarct size at 12 weeks (cardiac magnetic resonance). Secondary endpoints included indices of coronary microcirculatory function (index of microvascular resistance [IMR]), initial infarct size (troponin at 24 hours), final infarct size at 12 weeks (cardiac magnetic resonance), corrected thrombolysis in myocardial infarction (TIMI) frame count, TIMI flow grade, myocardial perfusion grade, and ST-segment resolution (ClinicalTrials.gov NCT02733341). Results P2Y12 inhibition at first balloon inflation time was significantly greater in cangrelor-treated patients (cangrelor P2Y12 reaction unit [PRU] 145.2 ± 50.6 vs. ticagrelor 248.3 ± 55.1). There was no difference in mean PRU at 4 and 24 to 36 hours post-dosing. IMR, final infarct size, angiographic and electrocardiographic measures of reperfusion were all similar between groups. Conclusion Cangrelor produces more potent P2Y12 inhibition at the time of first coronary balloon inflation time compared with ticagrelor. Despite this enhanced P2Y12 inhibition, coronary microvascular function and final infarct size did not differ between groups.

Cangrelor, Tirofiban, and Chewed or Standard Prasugrel Regimens in Patients With ST-Segment–Elevation Myocardial Infarction

“… 32 Alexopoulos et al 34 reported that HRPR was 6.7% at 15 minutes and 0% at 1 hour (using VerifyNow and a cutoff of PRU >208) in 15 patients with STEMI receiving cangrelor (pretreated with ticagrelor; none of them received morphine). Ubaid et al 35 reported an HRPR rate of 10% (using VerifyNow and a cutoff of PRU >208) at the time of balloon inflation in 50 cangrelor-treated patients with STEMI. In Buchtele et al, 36 16 cardiac arrest survivors with STEMI, who were treated with targeted temperature management, received cangrelor, and none had HRPR (using Multiplate Analyzer, platelet function had a median 18 U, interquartile range 10 to 25; <46 U was used as the cutoff).…”

Prolonged enoxaparin therapy compared with standard-of-care antithrombotic therapy in opiate-treated patients undergoing primary percutaneous coronary intervention

“…The lack of difference in ST resolution between the two strategies suggests a lack of differential effect on impairment of the microvascular circulation. Other work has shown that potent P2Y 12 inhibition at the time of PPCI with cangrelor did not translate into improvement in infarct size or microvascular circulation [24]. As such, it appears that antithrombotic treatment is needed as a preventative therapy rather than as an intervention to aid microvascular circulation.…”

“…As such, it appears that antithrombotic treatment is needed as a preventative therapy rather than as an intervention to aid microvascular circulation. Although cangrelor may be an attractive option to circumvent the delayed absorption of ticagrelor or prasugrel, it has only been studied as a 2-4 hour infusion, which may not be sufficient to cover the delayed onset of action of oral P2Y 12 inhibitors in all patients [14,24]. Furthermore, it may not be affordable in many healthcare settings to offer cangrelor as a routine 6-hour infusion to opiate-treated STEMI patients undergoing PPCI.…”

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

“…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. The administration of crushed prasugrel or ticagrelor resulted in faster platelet inhibition compared with ingestion of the whole tablet in the setting of STEMI.…”