Clopidogrel utilization in patients with coronary artery disease and diabetes mellitus: should we determine CYP2C192 genotype?

• Published in: European journal of clinical pharmacology Vol. 74; no. 12; pp. 1567 - 1574
• Main Authors: Chouchene, Saoussen, Dabboubi, Rym, Raddaoui, Haythem, Abroug, Hela, Ben Hamda, Khaldoun, Hadj Fredj, Sondess, Abderrazak, Fatma, Gaaloul, Mayssa, Rezek, Marwa, Neffeti, Fadoua, Hellara, Ilhem, Sassi, Mouna, Khefacha, Linda, Sriha, Asma, Nouira, Semir, Najjar, Mohamed Fadhel, Maatouk, Faouzi, Messaoud, Taieb, Hassine, Mohsen
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2018; Springer Nature B.V
• Subjects: Adult; Aged; Alleles; Biomedical and Life Sciences; Biomedicine; Blood platelets; Blood Platelets - drug effects; Cardiovascular disease; Clinical trials; Clopidogrel; Clopidogrel - therapeutic use; Coronary artery; Coronary Artery Disease - complications; Coronary Artery Disease - drug therapy; Coronary Artery Disease - genetics; Coronary vessels; Cross-Sectional Studies; Cytochrome P-450 CYP2C19 - genetics; Cytochrome P-450 CYP2C19 - metabolism; Cytochrome P450; Diabetes; Diabetes mellitus; Diabetes Mellitus - drug therapy; Diabetes Mellitus - genetics; Diabetic Angiopathies - drug therapy; Female; Gene polymorphism; Genetic factors; Genotype; Genotyping; Heart diseases; Heterozygote; Humans; Male; Middle Aged; Pharmacogenetics; Pharmacology/Toxicology; Platelet Aggregation Inhibitors - therapeutic use; Platelet Function Tests; Platelets; Polymerase chain reaction; Polymorphism, Genetic; Restriction fragment length polymorphism; Young Adult; Clopidogrel; Cytochrome P-450 CYP2C19; Coronary artery disease; Diabetes mellitus
• ISSN: 0031-6970; 1432-1041; 1432-1041
• DOI: 10.1007/s00228-018-2530-5

Purpose Clopidogrel non-responsiveness is multifactorial; several genetic and non-genetic factors may contribute to impaired platelet inhibition. The goal of this study is to determine the effect of the cytochrome P450 CYP2C19*2 polymorphism on the platelet response to clopidogrel in patients with and without diabetes mellitus (DM). Methods We conducted an observational study in patients with coronary artery disease and consequent exposure to clopidogrel therapy (75 mg/day for at least 7 consecutive days). We have analyzed two groups of patients: group I (DM patients) and group II (non-diabetes mellitus patients). Platelet reactivity was assessed by the VerifyNow P2Y12 assay and high on clopidogrel platelet reactivity (HPR) was defined as P2Y12 reaction units (PRU) ≥ 208. Genotyping for CYP2C19*2 polymorphism was performed by PCR-RFLP. Results We have included 150 subjects (76 DM and 74 non-diabetes mellitus patients). The carriage of CYP2C19*2 allele, in DM patients, was significantly associated to HPR (odds ratio (OR) 4.437, 95% confidence interval (CI) 1.134 to 17.359; p  = 0.032). Furthermore, 8.4% of the variability in percent inhibition by clopidogrel could be attributed to CYP2C19*2 carrier status. However, in non-diabetes mellitus patients, there was no significant difference in platelet response to clopidogrel according to the presence or absence of CYP2C19*2 allele carriage (OR 1.260, 95% CI 0.288 to 5.522; p  = 0.759). Conclusions Our study suggests that the carriage of CYP2C19*2 polymorphism, in DM patients, might be a potential predictor of persisting HPR in these high-risk individuals. Trial registration Clinical Trials.gov NCT03373552 (Registered 13 December 2017)