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

Kevin P. Bliden, Udaya S. Tantry, Robert F. Storey, Young Hoon Jeong, Martin Gesheff, Cheryl Wei, Paul A. Gurbel

Research output: Contribution to journalArticlepeer-review

Abstract

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 P2Y 12 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.

Original languageEnglish (US)
Pages (from-to)160-165
Number of pages6
JournalAmerican heart journal
Volume162
Issue number1
DOIs
StatePublished - Jul 2011

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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