Abstract 13031: A Randomized Trial Comparing the Effects of Ticagrelor versus Clopidogrel on Myocardial Perfusion in Patients With Coronary Artery Disease

Abstract

Introduction: Ticagrelor is a reversible P2Y12 receptor antagonist used in patients with acute coronary syndrome (ACS). In the PLATO trial, treatment with ticagrelor reduced mortality compared to clopidogrel, to which pleotropic mechanisms may have contributed. In this study, we compared the effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease on myocardial blood flow (MBF) at rest and during intermediate and high dose adenosine infusion. Methods: Patients (n=22) were randomized using a double-blind crossover design to ticagrelor 90 mg orally twice a day for 10 days and clopidogrel 75 mg orally once a day for 10 days, with a washout period of at least 5 days between the treatments. MBF was measured using Rb-82 PET-CT at baseline and at intermediate (80 mcg/kg/min) and high dose adenosine (140 mcg/kg/min). Results: Global MBF was significantly greater with ticagrelor versus clopidogrel at intermediate dose adenosine (1.28±0.55 versus 1.13±0.47, p=0.002), and not different at baseline (0.65±0.19 versus 0.60±0.15, p=0.4254) nor at high dose adenosine (1.64±0.40 versus 1.61±0.19, p=0.5302). In abnormal segments with low MBF reserve (<2.5), MBF was significantly greater with ticagrelor compared to clopidogrel at intermediate and high dose of adenosine (p<0.0001), with no difference at baseline. For segments with high MBF reserve (≥2.5 and < 3.5), segmental MBF was significantly greater with ticagrelor compared to clopidogrel at baseline (p<0.001) and at intermediate adenosine dose (p<0.0001). Conclusions: Global stress MBF was greater with ticagrelor compared to clopidogrel during intermediate dose adenosine infusion. Regional MBF in segments with reduced MBF reserve was greater with ticagrelor compared to clopidogrel during intermediate and high dose adenosine. This suggests that ticagrelor may potentiate adenosine-induced myocardial blood coronary flow increases in patients with stable CAD compared to clopidogrel; an effect that may explain the observed incremental mortality benefit observed with ticagrelor.