Ticagrelor and Endothelial Function: An Effect That Persists Far From the Acute Phase and in Monotherapy

Ticagrelor is an oral reversible inhibitor of the P2Y12 platelet receptor. From the first randomized clinical trial, which presented this drug to the cardiovascular panorama, it was clear that ticagrelor has something different compared with other P2Y12 inhibitors. In the PLATO trial (Study of Platelet Inhibition and Patient Outcomes), ticagrelor was superior to clopidogrel in the reduction of major cardiac and cerebrovascular adverse events.1 Surprisingly, the reduction of the composite primary end point was not only driven by a reduction in myocardial infarction (which was similar to the other newer P2Y12 inhibitor prasugrel), but also in cardiovascular mortality. This finding cannot be explained only by a stronger platelet inhibition as compared with clopidogrel. Indeed, prasugrel shows a similar platelet inhibition as compared with ticagrelor but did not affect cardiovascular mortality in any trials. Therefore, investigators looked for pleiotropic effects of ticagrelor, different from the one mediated by P2Y12 inhibition. Although with conflicting results, many studies reported that ticagrelor increased adenosine plasma level in patients with acute coronary syndrome (ACS) by inhibiting adenosine uptake by red blood cells2 and improved endothelial function, which is significantly impaired in patients with ACS or in other conditions characterized by acute/chronic inflammation.