Variability of on-treatment platelet reactivity in patients on clopidogrel

Abstract

Response to clopidogrel therapy is subject to inter-individual variability. However, data with regard to on-treatment platelet reactivity over time in patients undergoing coronary stenting are scarce. For this prospective observational study, 102 consecutive patients on dual antiplatelet therapy undergoing coronary stenting due to stable coronary artery disease (CAD; n = 29), non ST-elevation acute coronary syndrome (NSTE-ACS; n = 45) and ST-elevation myocardial infarction (STEMI; n = 28) were enrolled. Vasodilator-stimulated phosphoprotein-phosphorylation assay was performed at baseline, as well as 1, 3 and 6 months thereafter. Platelet reactivity index (PRI) measured after 1, 3 and 6 months was lower compared to baseline values (p < 0.001). Variables responsible for reduced response to clopidogrel at baseline (reticulated platelet fraction, simvastatin therapy) and during steady-state phase (body mass index, blood glucose concentrations, cholesterol/HDL-ratio and quality of life score) were different. High on-treatment platelet reactivity (HTPR)-phenotype (cut-off = 50% PRI) within the first month changed in 31% of stable CAD, 33% of NSTE-ACS and 39% of STEMI patients, respectively. HTPR-phenotype in the steady-state phase (month 1 to 6) changed in 45% of stable CAD, 33% of NSTE-ACS and 25% of STEMI patients. Response to clopidogrel and accordingly platelet function might vary over time, especially when a cut-off based approach, is used. There was a significant reduction of on-treatment platelet reactivity within the first month after percutaneous coronary intervention with stenting which was maintained for up to 6 months. Variables associated with reduced response to clopidogrel at baseline and during steady-state phase were different, as the latter mainly reflected an unfavorable metabolic profile, comprising elevated BMI, blood glucose levels as well as cholesterol/HDL-ratio.

Individual long-term variation of platelet reactivity in patients with dual antiplatelet therapy after myocardial infarction

“…The reason for the divergent results is not evident, but differences in study patient characteristics, (like age, comorbidity, other medication and proportion of patients with STEMI/ NSTE ACS) as well as timing of measurement and time of follow-up may be important factors. Important individual change in HPR status through 6-months follow-up, in patients treated with clopidogrel, has also been observed with other methods (26). Our data are in line with earlier data indicating a substantial change in individual HPR status over time, in patients treated with clopidogrel.…”

Ticagrelor: Pharmacokinetics, Pharmacodynamics, Clinical Efficacy, and Safety

“…Despite the widespread use of clopidogrel, there is a rate of recurrent cardiovascular (CV) events of at least 10% within 1 year of an ACS event . These events are potentially explained by issues related to clopidogrel including variability in antiplatelet response, pharmacogenomic influences, and drug interactions . The P2Y 12 ‐receptor inhibitor prasugrel overcame a number of limitations of clopidogrel but has a similar chemical structure (thienopyridine).…”

Does the response to aspirin and clopidogrel vary over 6 months in patients with ischemic heart disease?

“…A number of studies have performed longitudinal analyses of PR in clopidogrel-treated patients over time, and the results have again been discrepant [1,26,[32][33][34][35][36][37][38]. However, these studies investigated heterogeneous patient populations managed with different antiplatelet regimens and in whom platelet function testing was performed at varying intervals in relation to both clopidogrel loading and timing of PCI.…”

“…PRU and AUC15 ADP ), and in rates of HTPR while receiving clopidogrel from baseline. Increasingly, it is becoming recognized that prevalence of HTPR can vary significantly over time among clopidogrel-treated patients undergoing PCI [32,34,36,37]. For example, a study performed in 102 patients with stable CAD or ACS (including STEMI) showed that rates of HTPR as measured by the vasodilator-stimulated phosphoprotein-phosphorylation assay reduced significantly from 67% at baseline (i.e.…”

“…For example, a study performed in 102 patients with stable CAD or ACS (including STEMI) showed that rates of HTPR as measured by the vasodilator‐stimulated phosphoprotein‐phosphorylation assay reduced significantly from 67% at baseline (i.e. 6–24 h post‐PCI) compared with at 1 month (50%) . Furthermore, there were considerable changes in the OTPR phenotype in the first month (31–39%), during which there was a significant reduction in the PR index, but also after 1 month (25–45%) during which PR index was steady state.…”