CYP2C19 genetic variation and individualized clopidogrel prescription in a cardiology clinic

Abstract

Background: Clopidogrel (Plavix) is an antiplatelet medication that is routinely used in patients with cardiovascular disease. Cytochrome P2C19 enzymes play a major role in its metabolism, which determines its varied therapeutic level and its effectiveness.Objectives: To customize clopidogrel therapy and evaluate its efficacy by using CYP2C19 genotypic and phenotypic information to improve clinical outcomes in patients.Methods: A total of 465 patients with underlying cardiovascular disease were selected from our out-patient cardiology clinic. DNA sequences of CYP2C19 were analyzed in 465 patients.Results: Of 465 patients, 183 were wild-type homozygous (*1/*1) and 18.8% gain-of function and 19.8% loss-of-function alleles in our patient population The following changes were made: 1) Switching to prasugrel in patients whose genotype noted them to be “Slow metabolizers. This medication adjustment improved clinical outcomes in this patient group.2) Discontinuing or lowering clopidogrel doses in patients whose genotypes noted them to be “Fast or ultra-fast metabolizes” to decrease bleeding risk. For those who were not on clopidogrel but carried abnormal allele(s), “clopidogrel caution” was documented. These individuals were followed up for 3 years and there has not been any cardiac clinical symptoms, cardiac death or excessive bleeding reported.Conclusions: Given the varied effectiveness of clopidogrel due to its metabolism by CYP2C19 enzyme, and the relatively high frequency of both gain-of-function (18.8%) and loss-of-function (19.8%) alleles in our patient population, we believe that genotyping CYP2C19 is clinically important in order to improve patient outcomes and minimize patient risk.

CYP2C19*2, CYP2C19*17 and ITGB3 (PlA1/A2) polymorphisms and resulting therapeutic alterations of clopidogrel and aspirin: A clinical screening among CVD patients who undergone PCI

“…Our study was aimed to find a relationship between patients' genomic profile and their status of polymorphism with reduced scope for aspirin and clopidogrel metabolism. The outcome demonstrated for the presence of 35.9% wild type and 47.2% hetero and 16.9% mutant people who carried CYP2C19*2 variant allele which went in line with the studies conducted in the Malaysian [46], Chinese [47], Egyptian [48] and American [49] healthy population (Table 3) In the case of *17 carriers, a standard or reduced dose of clopidogrel and strict monitoring for potential bleeding of the patient was advised [51]. As stated by the current CPIC guidelines, the following changes are to be made:…”

“…2. Discontinuing or lowering clopidogrel doses in rapid metabolizer genotype to decrease bleeding risk [51].…”

Comparison of major bleeding in patients with acute coronary syndrome that underwent coronary artery bypass grafting treated with clopidogrel or ticagrelor: a systematic review and meta-analysis

“…In animal subjects, a study proposed that clopidogrel was found to have 3.5-fold associated with higher bleeding risk compared to ticagrelor 48 . Clopidogrel is metabolized by cytochrome P2C19 enzyme 49 , and recent gene-disease interaction studies reported that cytochrome P2C19 CYP2C19*20 C-889T>G (SNP rs11568732) was associated with the risk of bleeding in ACS patients treated with clopidogrel 50 – 52 . Therefore, theoretically, the risk of major bleeding with clopidogrel should be higher than with ticagrelor.…”

Farmacogenômica e Doença Cardiovascular: Onde Estamos e Para Onde Vamos

“…76 A resposta do indivíduo frente ao clopidogrel pode sofrer alteração, determinada pelo polimorfismo do CYP2C19. 77 A variante de perda de função do CYP2C19*2 foi associada a um risco aumentado de eventos cardiovasculares adversos, incluindo trombose de stent durante o tratamento com clopidogrel. 78 Mais especificamente, o alelo CYP2C19*2 (rs4244285) causa perda de função e foi associado à redução na atividade antiagregante do medicamento.…”