Clinical effects and outcomes with new P2Y12 inhibitors in ACS

Thienopyridines have become the cornerstone of treatment for percutaneous coronary intervention although no survival benefit has ever been shown with clopidogrel despite increasing loading doses. Newly developed P2Y12 inhibitors are more potent, more predictable, and have a faster onset of action than clopidogrel, characteristics that make them particularly attractive for high-risk percutaneous coronary intervention (PCI). Four new P2Y12 inhibitors have been tested each of them having particular individual properties. Prasugrel is an oral pro-drug leading to irreversible blockade of the P2Y12 receptor and is approved worldwide for ACS PCI. Ticagrelor is a direct-acting and reversible inhibitor of the P2Y12 receptor with potentially more pleiotropic effects. Cangrelor is an intravenous direct and reversible inhibitor of the P2Y12 receptor providing the highest level of inhibition, and elinogrel is an intravenous and oral P2Y12 antagonist with a direct and reversible action. Both prasugrel and ticagrelor, opposed to clopidogrel, have shown that stronger P2Y12 inhibition led respectively to significant 19 and 16% relative risk reduction of a similar primary end point combining cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. Both drugs showed a significant 0.6% absolute excess of TIMI major bleeding not related to CABG surgery. Because in clinical trials, patients perceived to be at higher risk of bleeding usually are excluded, the risk of major and even fatal bleeding might even be higher in a 'real-world' setting, i.e. in the elderly patient with comorbidities. On the other hand, these newly developed P2Y12 inhibitors decrease mortality after PCI compared with clopidogrel. The risk/benefit ratio is particularly favorable in PCI for patients with STEMI.