CYP2C19 rs4244285 variant association with efficacy of long-term statin therapy in patients after ST-elevation myocardial infarction

Abstract

Introduction Cardiovascular disease is the leading cause of death and disability in Europe [1]. Statin therapy is a cornerstone of secondary prevention after acute ischemic events such as myocardial infarction (MI), (class IA recommendation according to European Society of Cardiology (ESC) guidelines) [2]. Statins are competitive inhibitors of HMG-CoA reductase which mediates the first step of cholesterol biosynthesis. The reduction of intracellular cholesterol results in a decrease of low-density lipoprotein cholesterol (LDL-C) in blood plasma [3]. Atorvastatin and rosuvastatin are among the most frequently prescribed statins in Europe, including Lithuania. CYP2C19metabolizes at least 10 % of drugs used in clinical practice [5]. The relationship between patient's response to statin therapy and CYP2C19 variants has not yet been established by other studies [4]. Aim To determine the effect of CYP2C19 *2 (rs4244285) on the clinical effectiveness of statin therapy in patients with ST-elevation myocardial infarction (STEMI). Methods A total of 189 patients with ST-elevation myocardial infarction (STEMI) hospitalized at the Lithuanian University of Health Sciences, Cardiac Intensive Care Unit from January 2021 till January 2022 were enrolled in this prospective study. Statin therapy started at the day of hospital admission and it was prescribed according to the ESC guidelines for a long-term treatment. Blood samples were taken on the day of admission and after 6 months of treatment. Total lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglyceride cholesterol (TG-C) concentrations were checked in patient`s blood. CYP2C19 gene variants were analyzed using real-time PCR technique in the Laboratory of Molecular Cardiology of Institute of Cardiology of Lithuanian University of Health Sciences. Statistical analysis was performed using SPSS version 27. The normal distribution of data was not observed therefore nonparametric Kruskal - Wallis test was used for comparison of medians. The values were expressed as median, range, and percentages. A p-value < 0.05 was considered statistically significant. Results A total of 40 (21.2%) patients had CYP2C19 *1*2, 5 (2.7%) - *2*2 and 144 (76.2%) were wildtype homozygous patients (*1*1). The frequencies of rare (*2) and wild-type (*1) alleles established in this study were 0.13 and 0.87, respectively. Represented allele frequencies were distributed according to Hardy - Weinberg Equilibrium (p=0.56). During 6 months of statin treatment, lowest blood lipoprotein cholesterol levels and the highest effect of statin therapy was observed in *1*1 carriers: total lipoprotein cholesterol decreased by 1.84 (0.6-9) mmol/l, LDL-C– 1.29 (0.8-6.4) mmol/l, TG-C – 0.21 (0.3-7.9) mmol/l, but HDL-C increased by 1.17 (0.8-1.6)mmol/l. Lipoprotein levels were also reduced in *1*2 patients: total cholesterol – 0.45 (0.4-4.7) mmol/l, LDL-C – 0.235 (0.2-4) mmol/l, TG-C – 0.174 (0.2-1.3) mmol/l, respectively. HDL-C in*1*2 patients increased by 0.1 (0.4-1) mmol/l. The *2*2 patients had the slightest effect of statin therapy: total cholesterol was reduced by 0.12 (0.1-0.4) mmol/l, LDL-C – 0.2 (0-0.4) mmol/l, TGC – 0.03 (0-0.2) mmol/l. Reduction of lipoprotein cholesterol between genotypes *1*1, *1*2 and*2*2 was significant (p<0.036). Conclusions Results of this study showed that CYP2C19 gene rs4244285 variants may have a significant effect on long-term treatment with statins in patients after STEMI.