The Dogged Search for Cryptic Effects of Ticagrelor: Wishful Thinking or Real Benefits Beyond P2Y12 Inhibition?
Greater protection against ischemic event occurrences has been associated with lower levels of platelet reactivity to adenosine diphosphate in patients with high risk coronary artery disease (1-3). The latter observations serve as the basis of the "platelet hypothesis"- i.e. greater inhibition of P2Y12 =less thrombotic event occurrence (4). Ticagrelor, a cyclo-pentyl-triazolo-pyrimidine, is indisputably a more potent P2Y12 inhibitor than clopidogrel (5) and when administered to patients with acute coronary syndrome (ACS) in the PLATelet inhibition and patient Outcomes (PLATO) trial resulted in a reduction not only in myocardial infarction (MI) but also, vascular death as compared to clopidogrel (6). The observed reduction in vascular death has provided a strong impetus to search for mechanisms of benefit beyond greater P2Y12 inhibition which are not shared by other P2Y12 inhibitors - the "non-P2Y12 - mediated" hypothesis of ticagrelor. The latter hypothesis is largely based on the property of ticagrelor to inhibit adenosine reuptake, thereby, increasing systemic and tissue adenosine levels (7). Most of the subsequent beneficial effects proceed downstream for this pivotal step, as adenosine has been proposed as an important molecule that attenuates ischemia-reperfusion injury.
- non-P2Y12-mediated effects
- P2RY12 receptor thrombosis
- platelet inhibitor
- ischemia reperfusion injury
- Received August 17, 2016.
- Revision received August 31, 2016.
- Accepted September 20, 2016.