Key result
Ticagrelor cuts platelet reactivity ~63% versus clopidogrel in nonresponders, matching responder inhibition.
Why the study?
Does ticagrelor, ticlopidine, high-dose clopidogrel, or triple therapy improve platelet reactivity in clopidogrel nonresponders after coronary stenting?
RCT (n=376)
Single-blind
Randomized crossover
Yes
Does ticagrelor, ticlopidine, high-dose clopidogrel, or triple therapy improve platelet reactivity in clopidogrel nonresponders after coronary stenting?
Absolute Event Rate: 26.1% vs 71.4%
p-value: p=<0.001
Ticagrelor effectively overcomes high platelet reactivity in clopidogrel nonresponders regardless of CYP2C19 metabolizer phenotype, unlike other antiplatelet strategies.
Ticagrelor may be prioritized in clopidogrel nonresponders post-stenting; extends mixed RCT data on achieving phenotype-independent platelet inhibition.
BACKGROUND/AIMS: Several interventions exist for overcoming high platelet reactivity (HPR) on clopidogrel therapy. The goal of this study was to identify strategies that improve inhibition of platelet reactivity in clopidogrel nonresponders with or without loss of function CYP2C19 genotypes, resulting in platelet reactivity similar to that in responders. METHODS: A total of 376 patients with stenting for coronary artery disease underwent platelet function testing in three centers. Blinded platelet function tests were performed after 75 mg daily clopidogrel treatment for 28 days. In total, 183 nonresponders were genotyped, were randomized to four treatment groups with each treatment lasting approximately 28 days, and underwent repeated measurements of platelet reactivity after treatment. RESULTS: With 75 mg of daily clopidogrel, nonresponders had significantly higher HPR than did responders (multiple electrode aggregometry [MEA, arbitrary platelet aggregation unit]: mean, 71.4; 95% confidence intervals [CI], 68.6 to 74.3; and mean, 27.5; 95% CI, 26.0 to 28.9, respectively; p < 0.001). Ticagrelor or ticlopidine treatment in nonresponders resulted in platelet reactivity similar to that in responders in intermediate metabolizers (mean, 24.0; 95% CI, 19.6 to 28.4; p > 0.05; and mean, 30.0; 95% CI, 24.7 to 37.5; p > 0.05, respectively) and poor metabolizers (mean, 23.2; 95% CI, 18.0 to 28.3; p > 0.05; and mean, 30.3; 95% CI, 24.5 to 6.0; p > 0.05, respectively). However, in extensive metabolizers, only ticagrelor treatment showed platelet reactivity similar to that in responders (mean, 26.1; 95% CI, 24.1 to 28.0; p > 0.05). CONCLUSIONS: Among clopidogrel nonresponders with cardiovascular disease on 75 mg daily clopidogrel, ticagrelor resulted in a comparable degree of platelet inhibition in all nonresponders compared with 150 mg daily clopidogrel or triple therapy with clopidogrel and cilostazol, irrespective of phenotype.
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Ko et al. (2018) conducted an RCT in Coronary artery disease with stenting (clopidogrel nonresponders) (n=376). Ticagrelor, ticlopidine, 150 mg clopidogrel, or triple therapy vs. Clopidogrel 75 mg daily was evaluated on Platelet reactivity (MEA arbitrary units) (95% CI 24.1-28.0, p=<0.001). Among clopidogrel nonresponders, ticagrelor significantly reduced platelet reactivity to 26.1 U compared to 71.4 U with 75 mg clopidogrel, achieving comparable inhibition to responders across all CYP2C19 phenotypes.
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