Variability of platelet response to clopidogrel is not related to adverse cardiovascular events in patients with stable coronary artery disease undergoing percutaneous coronary intervention

• Published in: European journal of clinical pharmacology Vol. 73; no. 9; pp. 1085 - 1094
• Main Authors: Olędzki, Szymon, Kornacewicz-Jach, Zdzisława, Safranow, Krzysztof, Kiedrowicz, Radosław, Gawrońska-Szklarz, Barbara, Jastrzębska, Maria, Gorący, Jarosław
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.09.2017; Springer Nature B.V
• Subjects: Age; Aged; Angioplasty; Aspirin; Biomedical and Life Sciences; Biomedicine; Blood platelets; Blood Platelets - drug effects; Blood pressure; Cardiovascular disease; Cardiovascular diseases; Clinical Trial; Clopidogrel; Coronary artery; Coronary artery disease; Coronary Artery Disease - drug therapy; Coronary Artery Disease - genetics; Coronary Artery Disease - metabolism; Coronary Artery Disease - surgery; Coronary vessels; Creatinine; Diabetes mellitus; Drug delivery; Female; Gene polymorphism; Genotype; Genotyping; Heart; Heart diseases; Hemorrhage; Humans; Impedance; Implantation; Implants; Ischemia; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate analysis; Percutaneous Coronary Intervention; Pharmacology; Pharmacology/Toxicology; Platelet Aggregation Inhibitors - adverse effects; Platelet Aggregation Inhibitors - pharmacokinetics; Platelet Aggregation Inhibitors - pharmacology; Platelet Aggregation Inhibitors - therapeutic use; Platelet Function Tests; Platelets; Polymorphism, Genetic; Reactivity; Single-nucleotide polymorphism; Stents; Survival analysis; Ticlopidine - adverse effects; Ticlopidine - analogs & derivatives; Ticlopidine - pharmacokinetics; Ticlopidine - pharmacology; Ticlopidine - therapeutic use; Stable coronary artery disease; Clopidogrel; Percutaneous coronary intervention; High on-treatment platelet reactivity; Clopidogrel response
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-017-2271-x

Background Antiplatelet response to clopidogrel and its influence upon the risk of cardiovascular adverse events among patients with stable coronary artery disease undergoing percutaneous coronary intervention (PCI) has not been investigated fully. Methods Two hundred eleven patients treated with aspirin and clopidogrel were included in the study. Immediately before PCI, residual platelet reactivity testing with impedance aggregometry assay and a single-nucleotide polymorphism genotyping analysis targeting variants of CYP2C19 , ABCB1 , and PON1 genes was performed. After the index PCI, the patients were screened for cardiovascular events 6 months following bare-metal stent implantation or 12 months following drug-eluting stent implantation. Results High on-treatment platelet reactivity (HTPR) was observed in 19.43% individuals and low-TPR (LTPR) in 26.54%. In multivariate analysis, HTPR was significantly ( p  < 0.05) associated with a history of diabetes, higher systolic blood pressure, and platelet count comparing to that of other patients. LTPR was significantly associated with no history of hypertension, younger age, lower platelet count, absence of the CYP2C19*2 variant, and lower CRP plasma level. Overall, cardiac adverse events were noted in 14.23% patients. Survival analysis with the Cox proportional hazard model showed no influence of residual platelet reactivity during clopidogrel therapy upon both ischemic and hemorrhagic events. However, significant predictors for composite of major adverse cardiac events and hospitalization for cardiovascular causes were identified (the higher CCS class prior to coronary intervention and the higher creatinine serum concentration). Conclusions The platelet response to clopidogrel has no impact upon post-procedural adverse events at mid-term follow-up in patients with stable CAD undergoing PCI. This finding suggests that routine platelet reactivity testing is not beneficial in this group of patients.