Randomized Trial Comparing the Effects of Ticagrelor Versus Clopidogrel on Myocardial Perfusion in Patients With Coronary Artery Disease

• Published in: Journal of the American Heart Association Vol. 6; no. 5
• Main Authors: Pelletier-Galarneau, Matthieu, Hunter, Chad R R N, Ascah, Kathryn J, Beanlands, Rob S B, Dwivedi, Girish, deKemp, Robert A, Chow, Benjamin J W, Ruddy, Terrence D
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 02.05.2017; Wiley
• Subjects: adenosine; Adenosine - administration & dosage; Adenosine - adverse effects; Adenosine - analogs & derivatives; Administration, Oral; Aged; clopidogrel; Coronary Artery Disease - diagnostic imaging; Coronary Artery Disease - drug therapy; Coronary Artery Disease - physiopathology; Coronary Circulation - drug effects; Coronary Vessels - diagnostic imaging; Coronary Vessels - drug effects; Coronary Vessels - physiopathology; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; myocardial blood flow; Myocardial Perfusion Imaging - methods; Ontario; Original Research; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - adverse effects; positron emission tomography; Positron Emission Tomography Computed Tomography; Predictive Value of Tests; Radiopharmaceuticals - administration & dosage; Rubidium Radioisotopes - administration & dosage; ticagrelor; Ticlopidine - administration & dosage; Ticlopidine - adverse effects; Ticlopidine - analogs & derivatives; Time Factors; Treatment Outcome; Vasodilator Agents - administration & dosage; adenosine; clopidogrel; ticagrelor; myocardial blood flow; positron emission tomography
• ISSN: 2047-9980; 2047-9980
• DOI: 10.1161/JAHA.117.005894

Ticagrelor is a P2Y receptor inhibitor used in acute coronary syndromes to reduce platelet activity and to decrease thrombus formation. Ticagrelor is associated with a reduction in mortality incremental to that observed with clopidogrel, potentially related to its non-antiplatelet effects. Evidence from animal models indicates that ticagrelor potentiates adenosine-induced myocardial blood flow (MBF) increases. We investigated MBF at rest and during adenosine-induced hyperemia in patients with stable coronary artery disease treated with ticagrelor versus clopidogrel. This randomized double-blinded crossover study included 22 patients who received therapeutic interventions of 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 10 days between the treatments. Global and regional MBF and myocardial flow reserve were measured using rubidium 82 positron emission tomography/computed tomography at baseline and during intermediate- and high-dose adenosine. Global MBF was significantly greater with ticagrelor versus clopidogrel (1.28±0.55 versus 1.13±0.47 mL/min per gram, =0.002) at intermediate-dose adenosine and not different at baseline (0.65±0.19 versus 0.60±0.15 mL/min per gram, =0.084) and at high-dose adenosine (1.64±0.40 versus 1.61±0.19 mL/min per gram, =0.53). In regions with impaired myocardial flow reserve (<2.5), MBF was greater with ticagrelor compared with clopidogrel during intermediate and high doses of adenosine ( <0.0001), whereas the differences were not significant at baseline. Ticagrelor potentiates global and regional adenosine-induced MBF increases in patients with stable coronary artery disease. This effect may contribute to the incremental mortality benefit compared with clopidogrel. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01894789.