Personalized trimetazidine prescription as a cytoprotective agent in patients with coronary artery disease

Abstract

Aim. To develop a personalized approach to the trimetazidine use in patients with coronary artery disease (CAD) based on the criteria for predicting the cytoprotective activity tested in vitro.Material and methods. We examined 30 patients with class I-III stable effort angina with concomitant hypertension and heart failure. The patients underwent echocardiography, complete blood count, biochemical tests with determination of the lipid profile, creatine phosphokinase (CPK), CPK-MB, renal and hepatic parameters. To determine the cytoprotective activity of trimetazidine, white blood cells (WBCs) of patients were examined in vitro using an Eclipse Ti-U inverted fluorescence microscope (Nikon, Japan). Living and dead cells were determined by staining WBCs with fluorescent dyes (Calcein AM, Ethidium bromide). Cell viability index (CVI) was calculated. The statistical processing was carried out. The criteria for predicting the trimetazidine cytoprotective effect were determined using Wald statistics.Results. When trimetazidine was injected into a WBC suspension sample, two types of cell viability changes were observed: in 60% of patients, CVI increased, on average, by 37% (from 23% to 60%, p<0,001) and in 40% of patients, CVI decreased, on average, by 30% (from 54% to 24%, p<0,05).A number of conditions of the patient initial status were identified for the manifestation of trimetazidine cytoprotective activity: grade 1 hypertension; right ventricular end diastolic dimension up to 30 mm according to echocardiography; normal lipid profile with a total cholesterol <5,3 mmol/L, very-low-density lipoproteins <1 mmol/L and an atherogenic coefficient up to 3 CU, myocyte and cardiomyocyte destruction (total CPK >100 U/L and CPK-MB >15 U/L), normal liver function (alanine aminotransferase <25 U/L), renal dysfunction (total protein <75 g/L, urea >8 mmol/L and blood creatinine >100 pmol/L), normal thrombopoiesis (immature platelet fraction <5%) and the state of functional adaptive system resistance (blood lymphocytes <30% and neutrophils >4x109/L).Conclusion. According to this in vitro analysis, the trimetazidine significantly increases (by an average of 37%) the cell (WBC) viability in 60% of patients with CAD. There are conditions of patient initial status, which specifies an individual pharmacodynamic target for the cytoprotective action of the drug.