Abstract

Thienopyridines have become the cornerstone of treatment of percutaneous coronary intervention although no survival benefit has ever been shown with clopidogrel despite increasing loading doses. Newly developed P2Y(12)inhibitors are more potent, more predictable and have a faster onset of action than clopidogrel, characteristics that make them particularly attractive for high-risk PCI. Four new P2Y(12)inhibitors have been tested each of them having particular individual properties. Prasugrel is an oral prodrug leading to irreversible blockade of the P2Y(12)receptor and is approved worldwide for ACS PCI. Ticagrelor is a direct-acting and reversible inhibitor of the P2Y(12)receptor with potentially more pleiotropic effects. Cangrelor is an intravenous direct and reversible inhibitor of the P2Y(12)receptor providing the highest level of inhibition and elinogrel is an intravenous and oral P2Y(12)antagonist with a direct and reversible action. Both prasugrel and ticagrelor, opposed to clopidogrel, have shown that stronger P2Y(12)inhibition led respectively to significant 19% and 16% relative risk reduction of a similar primary endpoint combining cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Both drugs showed a significant 0.6% absolute excess of TIMI major bleeding not related to CABG surgery. The effect of these new compounds is prompt, predictable and powerful as compared to clopidogrel. Their net benefit is particularly marked in PCI for STEMI patients, in which there is no significant increase in major bleeding when compared with clopidogrel. However, because in clinical trials patients perceived to be at higher risk for 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.

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