Ticagrelor Induces Ischemic Preconditioning in Stable Patients Undergoing Percutaneous Coronary Intervention: The TAPER-S Randomized Study

Background: Ticagrelor is an oral P2Y12 inhibitor associated with improved clinical outcomes in patients with acute coronary syndrome compared with clopidogrel. Ticagrelor also inhibits cellular uptake of adenosine and enhances adenosine-mediated hyperemia in animal and human models. Objectives: We sought to investigate whether ticagrelor, as compared to clopidogrel, could increase ischemic preconditioning in stable patients undergoing PCI.Methods: This was a prospective, randomized, blinded, end-point trial enrolling stable patients with coronary artery disease (CAD) requiring fractional flow reserve (FFR)-guided PCI of intermediate coronary lesions. The primary endpoint of the study was the comparison of the delta (Δ) (difference) ST-segment elevation measured by intracoronary-ECG during two-step sequential coronary balloon inflations in the culprit vessel between clopidogrel and ticagrelor arms. The study was stopped early because the primary endpoint was met at a prespecified interim analysis. Fifty-three patients were randomized to either clopidogrel or ticagrelor. Results: Ischemic preconditioning was assessed by measuring the ST-segment elevation at intracoronary ECG during a two-step sequential coronary balloon inflations in the reference vessel, during PCI. ΔST-segment elevation was significantly higher in ticagrelor as compared to clopidogrel (p<0.0001). Ticagrelor was associated with a lower angina score during coronary balloon inflations, but there was no difference in coronary microvascular resistance between groups. Conclusions: Ticagrelor induces ischemic preconditioning among patients with stable CAD undergoing PCI. Although adenosine serum concentrations were increased in patients treated with ticagrelor as compared to those treated with clopidogrel, further studies are warranted to explore potential mechanisms through which ticagrelor induces ischemic preconditioning.