Endothelioprotective effect of a combination of statin with antioxidant in the treatment of patients with coronary heart disease

Abstract

Introduction: The widespread prevalence and mortality from coronary heart disease (CHD) determine the urgency of the problem of finding rational drug combinations for more effective treatment of this pathology. Endothelium of the vessels is the target organ for pharmacological correction of cardiovascular pathology. We suggested that the combination of statin with an antioxidant may be rational in terms of endothelial dysfunction correction in the treatment of patients with coronary artery disease, which this work is devoted to. Research tasks: The aim of this research was to study the rationality of the combination of statin (atorvastatin) and antioxidant (ethoxidol) in relation to endothelioprotection in the treatment of patients with CHD. Material and Methods: We conducted a prospective, open, randomized controlled comparative study of 60 patients with CHD: stable angina pectoris, which were divided into two groups: 1st (control, n = 30) - patients who received basic therapy for stable angina pectoris with an average dose of atorvastatin 20mg per day and 2nd (study group, n = 30) - patients receiving additional ethoxidol at a dose of 300 mg per day in tablets for 50-54 days while reducing the dosage of atorvastatin to 10 mg per day. In addition, 20 practically healthy individuals were examined. Endothelial function was evaluated based on a study of three indicators in the blood - the Willibrandt factor (FVB) by photoelectrocolorimetry, as well as endothelin-1 and endothelial nitric oxide synthase (e-NOS) by enzyme-linked immunosorbent assay. The endothelial function index was calculated as the ratio of the vasodilation marker and vasoconstriction marker: e-NOS / endothelin-1. Materials were processed statistically. Results: the activity of FVB during the treatment significantly decreased - in the 1st group by 42% (p<0.001) and in the 2nd group by 50% (p<0.001); no differences between the groups were observed. The level of endothelin-1 in the blood also significantly decreased in the dynamics of treatment of patients with CHD: in the 1st group from 29.32±3.22 pkg/ml to 17.54±1.88 pkg/ml (p<0.001), and in the 2nd group - from 26.71±3.69 pkg/ml to 16.61±2.14 pkg/ml (p<0.05), while in the 1st and 2nd groups the level of endothelin-1 was not achieved healthy individuals (8.47±1.18 pcg / ml). The level of eNOS significantly increased during the treatment in both groups of patients: in the 1st group from 82.69±6.52 pkg/ml to 156.40±14.18 pkg/ml (p<0.001) and in the 2nd group - from 85.17±5.37 pkg/ml to 148.16±9.47 pkg/ml (p<0.001), without reaching the level of eNOS of practically healthy individuals (222.97±11.38 pkg/ml). The endothelial function index increased during the treatment in both groups: in the 1st - from 2.82 to 8.92 (p<0.001) and in the 2nd - from 3.19 to 8.92 (p<0.001), also without reaching the level of this indicator for healthy individuals (26.32). Conclusion: It has been obtained the evidence of the rationality of the combination of statin with an antioxidant in achieving the endothelioprotective effect of treatment of patients with CHD. Reducing the dosage of atorvastatin while taking the antioxidant drug ethoxidol allows you to achieve a comparable endothelioprotective effect.