Pharmacodynamic effects of cangrelor in patients with or without STEMI undergoing percutaneous coronary intervention: insights from the POMPEII study

Aims: Cangrelor is approved for oral P2Y12 inhibitor naïve patients undergoing percutaneous coronary intervention (PCI). Pharmacodynamic (PD) investigations in different clinical settings, using various assays, have shown contrasting data in terms of entity of platelet inhibition and rates of high residual platelet reactivity (HRPR). We assessed the PD effects in patients with or without ST elevation myocardial infarction (STEMI) receiving cangrelor during PCI. Methods and results: The PharmacOdynaMic effects of cangrelor in PatiEnts wIth acute or chronIc coronary syndrome undergoing percutaneous coronary intervention (POMPEII) registry (NCT04790032) is an investigator-initiated, prospective study assessing PD at four time points with three assays. From March 2021 to June 2024, 126 patients naïve from oral P2Y12 inhibitors underwent PCI with cangrelor [32 with STEMI and 94 without (NSTE-ACS = 30, CCS = 64)]. All STEMI patients switched from cangrelor to ticagrelor, while most patients without STEMI switched to clopidogrel. Inhibition of platelet aggregation (IPA%) during cangrelor infusion was lower in patients with STEMI compared with those without STEMI (LTA 20-μM-ADP 51.5 ± 16.2% vs. 59.7 ± 16.2%; P = 0.017). Conversely, after switching from cangrelor to an oral P2Y12 inhibitor, IPA was greater in patients with STEMI compared with those without STEMI. Rates of HRPR were consistent with lower platelet inhibition in STEMI during cangrelor and greater after its discontinuation compared with patients without STEMI. Within STEMI patients, cangrelor-induced IPA was lower compared with ticagrelor-induced IPA (P = 0.036). Conclusion: Cangrelor-induced platelet inhibition was lower in patients with STEMI compared with those without STEMI and was lower than that induced by ticagrelor among STEMI patients. The switch from cangrelor to an oral P2Y12 inhibitor exposed patients without STEMI to greater HRPR compared with those with STEMI.