Evaluation of the efficacy of combined pharmacoprotection with ticagrelor and high-dose statins in patients with myocardial infarction and different genotypes of rs2305948 VEGFR2

Aim of the study was to evaluate the effect of ticagrelor treatment in combination with high-dose statins on the relative risk of ischemic cardiovascular events during long-term follow-up in patients with myocardial infarction (MI) carrying different genotypes of rs2305948 VEGFR2. Material and methods. The study included 218 patients with acute MI, including 23 % women , average age 58 [52; 64] years. After the initial examination and preparation in the hospital emergency department, patients underwent coronary angiography followed by percutaneous coronary intervention or coronary artery bypass grafting. Two groups were identified for further observation in accordance with the therapy mode: 1 – individuals who received treatment with ticagrelor (12 months) and high-dose statins (≥ 12 months) after MI (n = 48, 22 %), 2 – individuals who took other drug combinations of statins in low or high doses in combination with various platelet P2Y12 receptor inhibitors – clopidogrel or ticagrelor (n = 170, 78 %). All 218 patients underwent genotyping (C/C, C/T, T/T) rs2305948 VEGFR2 using real-time polymerase chain reaction. The duration of outpatient observation of these patients was 9 years (2015–2024) after MI. Results. It was established that in the first group, in 48 individuals, along with 6 (13 %) identified heterozygous (C/T) genotypes of rs2305948 VEGFR2, 42 (87 %) cases with the homozygous genotype C/C were also identified, and in the second group, in 170 individuals, along with 70 (41 %) heterozygous C/T and homozygous T/T genotypes, 100 (59 %) cases with the homozygous genotype C/C rs2305948 VEGFR2 were identified (χ2 = 13.56, p < 0.001). In patients with MI in the first group, who received treatment with ticagrelor in combination with high-dose statins, there was a lower incidence of cardiovascular death (p = 0.024), recurrent acute coronary syndrome (p = 0.011), repeat myocardial revascularization (p = 0.025) and a combined end point (CEP) (p < 0.001) than among patients in group 2 who received other drug combinations of statins in high or low doses and P2Y12 platelet inhibitors. In a multivariate analysis using binary logistic regression, the Charlson comorbidity index increased the relative risk of CEP by 2.2 times (p < 0.001), the C/T and T/T rs2305948 VEGFR2 genotypes increased by 2.1 times (p = 0.023), and baseline three-vessel coronary disease increased by 2.3 times (p = 0.001). At the same time, treatment with ticagrelor in combination with high-dose statins reduced the risk of CEP by 72 % (p = 0.005), achieving low-density lipoprotein cholesterol level less than 1.4 mmol/l within 3 years after MI by 54 % (p = 0.044), and the use of drug-eluting stents by 45 % (trend, p = 0.093). Conclusions. In long-term follow-up (9 years) in patients with MI, the relative risk of ischemic cardiovascular events is directly determined by the C/T and T/T rs2305948 VEGFR2 genotypes, severe comorbidity, and baseline three-vessel coronary disease. The relative risk of ischemic events is inversely determined by treatment with ticagrelor in combination with high-dose statins and achievement of target low-density lipoprotein cholesterol level after MI.

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