Gasanov I. Clinical and instrumental assessment of metoprolol succinate efficacy in patients with chronic heart failure on the background of obesity: genetic aspects of individual sensitivity and tolerability.

The study is devoted to the actual problem of modern medicine - increasing the effectiveness of treatment of patients with heart failure with obesity based on its clinical and instrumental assessment, taking into account the genetic characteristics of pharmacotherapy with metoprolol succinate beta-adrenoblocker. For the first time the frequency of occurrence of the 1846G/A polymorphism of the CYP2D6 gene of the cytochrome P450 system in patients with CHF and obesity was determined, and the association of the carriage of an unfavorable allele A with the increase in body weight of patients was established. The best indicators of the clinical status of patients for CHOCs and quality of life in the Minnesota questionnaire were revealed in the presence of GG than the GA genotype. It has been established that the use of metoprolol succinate in patients with heart failure and reduced left ventricular ejection fraction on the background of obesity, which are carriers of CYP2D6 gene polymorphism variant 1846G/G, is associated with a more pronounced positive dynamics of treatment efficacy. For the first time, it has been shown that in contrast to the carriers of the genotype 1846G/A, in patients with the GG genotype, there was a significant increased exercise tolerance in the 6-minute walk test (p <0.05), improvement in the pump function and volume parameters of the heart, and and normalization of parameters of vegetative balance. At the same time, it was found that in patients with genotype GA, a more pronounced decrease in heart rate was observed in comparison with those with a GG genotype (p <0.05). Complementary data on the incidence and nature of side effects when using metoprolol succinate in patients with various polymorphic variants of the 1846G/A polymorphism of the CYP2D6 gene. It was found that treatment with metoprolol succinate in patients with CHF and obesity, which carries the genotype 1846G/A of the CYP2D6 gene, is associated with a higher incidence of side effects than the GG genotype. The method of factor analysis revealed pathophysiologically grounded groups of factors of development of the pathological process in patients with CHF on the background of obesity, and on this basis prognostic models designed for differentiated appointment of metoprolol succinate in this category of patients were developed, tested and implemented in practical health care.