What Are Optimal P2Y12 Inhibitor and Schedule of Administration in Patients With Acute Coronary Syndrome?

Abstract

Guidelines recommend treatment with a P2Y12 platelet adenosine diphosphate receptor inhibitor in patients undergoing elective or urgent percutaneous coronary intervention (PCI), but the optimal agent or timing of administration is still not clearly specified. The P2Y12 inhibitor was initially used for its platelet anti-aggregatory action to block thrombosis of the recanalized coronary artery or deployed stent. It is now recognized that these agents also offer potent cardioprotection against a reperfusion injury that occurs in the first minutes of reperfusion if platelet aggregation is blocked at the time of reperfusion. But this is difficult to achieve with oral agents which are slowly absorbed and often require time-consuming metabolic activation. Patients with ST-segment elevation myocardial infarction who usually have a large mass of myocardium at risk of infarction seldom have sufficient time for upstream-administered oral agents to achieve a therapeutic P2Y12 level of inhibition by the time of balloon inflation. However, optimal treatment could be assured by initiating an IV cangrelor infusion shortly prior to stenting followed by subsequent post-PCI transition to an oral agent, that is, ticagrelor, once success of the recanalization and absence of need for surgical intervention are confirmed. Not only should this sequence provide optimal protection against infarction, it should also negate bleeding if coronary artery bypass grafting should be required since stopping the cangrelor infusion at any time will quickly restore platelet reactivity. It is anticipated that cangrelor-induced myocardial salvage will help preserve myocardial function and significantly diminish postinfarction heart failure.

Ticagrelor: clinical development and future potential

“…These observations were contrary to the findings from pre-clinical animal experiments demonstrating that early exposure of ticagrelor has pleiotropic cardioprotective effects that attenuate myocardial infarct size following coronary occlusion and reperfusion [138], to a greater degree than clopidogrel [139,140]. This has implications for the choice of initial antiplatelet agent in the management of STEMI patients [141]. It has been observed that the enteric absorption of ticagrelor is often delayed in STEMI patients, especially when opiates such as morphine are coadministered for pain relief [76][77][78][79].…”

“…Administration of a parenteral P2Y 12 inhibitor that reaches the circulation within minutes and prior to emergency PCI could potentially optimise the salvage of ischaemic myocardium and minimise reperfusion injury, in addition to providing early platelet inhibition to prevent stent thrombosis. Further work is therefore required to assess the benefit of intravenous cangrelor or subcutaneous selatogrel prior to stenting, followed by subsequent transition to oral ticagrelor [87,141,143,144].…”

Machine Learning for the ECG Diagnosis and Risk Stratification of Occlusion Myocardial Infarction at First Medical Contact

“…Furthermore, until now, clinicians never had sensitive nor highly speci c tools that would allow the ultra-early identi cation of OMI in the absence of a STEMI pattern. Such enhanced diagnostics can allow the design and implementation of prospective interventional trials to assess the therapeutic effectiveness of targeted interventions in this vulnerable group (e.g., early upstream P2Y 12 inhibitor administration, 54 emergent vs. delayed reperfusion therapy, 55 glucose-insulin-potassium infusion, 56 etc. ).…”

Translation of experimental cardioprotective capability of P2Y12 inhibitors into clinical outcome in patients with ST-elevation myocardial infarction

“…Careful selection of high-risk patients [11,12] and multitarget cardioprotective strategies may increase the protective potential [23,33]. Since intravenous cangrelor may have similar cardioprotective efficacy as ticagrelor, an alternative treatment strategy might be intravenous cangrelor infusion shortly prior to stenting followed by subsequent post-PCI transition to an oral agent [17].…”