The effect of ticagrelor versus clopidogrel on high on-treatment platelet reactivity: Combined analysis of the ONSET/OFFSET and RESPOND studies

• Published in: The American heart journal 2011-07, Vol.162 (1), p.160-165
• Main Authors: Bliden, Kevin P., MBA, Tantry, Udaya S., PhD, Storey, Robert F., MD, Jeong, Young-Hoon, MD, PhD, Gesheff, Martin, BS, Wei, Cheryl, PhD, Gurbel, Paul A., MD, FACC
• Format: Article
• Language: English
• Subjects: Acute coronary syndromes; Adenosine - administration & dosage; Adenosine - analogs & derivatives; Adenosine - pharmacokinetics; Administration, Oral; Aged; Aspirin - administration & dosage; Aspirin - therapeutic use; Biological and medical sciences; Blood platelets; Cardiology. Vascular system; Cardiovascular; Cardiovascular disease; Coronary Artery Disease - blood; Coronary Artery Disease - drug therapy; Coronary vessels; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug dosages; Drug therapy; Drug Therapy, Combination; Family medical history; Female; Flow cytometry; Follow-Up Studies; Heart attacks; Humans; Male; Medical sciences; Middle Aged; Patients; Phosphorylation; Platelet Activation - drug effects; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - pharmacokinetics; Purinergic P2Y Receptor Antagonists - administration & dosage; Purinergic P2Y Receptor Antagonists - pharmacokinetics; Retrospective Studies; Studies; Ticlopidine - administration & dosage; Ticlopidine - analogs & derivatives; Ticlopidine - pharmacokinetics; Time Factors; Treatment Outcome
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1016/j.ahj.2010.11.025

Objectives The objective of the study was to determine the prevalence of high on-treatment platelet reactivity (HPR) in coronary artery disease patients enrolled in the ONSET/OFFSET and RESPOND studies. Background HPR has been linked to the occurrence of adverse events after stenting in patients treated with clopidogrel (C) and aspirin. Prevalence of HPR after treatment with ticagrelor (T), a reversible oral P2Y12 receptor antagonist developed to overcome the limitations of C, is unknown. Methods Patients were treated with T (n = 106) or C (n = 103) on top of aspirin therapy. HPR was defined by published cutoff points associated with post–percutaneous coronary intervention ischemic risk: >59% 20 μM adenosine diphosphate–induced aggregation (light transmittance aggregometry), >235 P2Y12 reaction unit by VerifyNow P2Y12 assay (VerifyNow, San Diego, CA), and >50% platelet reactivity index by vasodilator-stimulated phosphoprotein phosphorylation assay (VASP-P). Proportion differences for T versus C were analyzed by χ2 test for each time point. Correlations ( R ) were analyzed by the Pearson method. Results Ticagrelor was associated with a significantly lower prevalence of HPR (0%-8%) compared with C (21%-81%) at 2, 4, 8, and 24 hours and ≥2 weeks postdosing ( P < .0001, for all assays). The R values between light transmittance aggregometry and VerifyNow/VASP-P were all ≥0.43, P < .0001. Conclusions The above data represent the largest serial pharmacodynamic evaluation of the comparative effects of T versus C. Ticagrelor was rapidly and consistently associated with a very low prevalence of HPR compared with C, as determined by multiple established methods to measure platelet reactivity. These results provide a mechanism for the lower ischemic event rate associated with T therapy reported in the PLATO trial.