The influence of genetic resistance to antiplatelet agents on clinical and laboratory parameters and outcomes in ST-segment elevation myocardial infarction
DOI: https://dx.doi.org/10.18565/pharmateca.2023.9-10.84-94
D.S. Markhulia, K.A. Popugaev, S.S. Petrikov, I.M. Kuzmina, G.A. Ghazaryan, K.V. Kiselev, D.A. Kosolapov, E.V. Klychnikova, M.A. Godkov, M.V. Parkhomenko, A.I. Kramarenko, S.A. Golovanev, K.B. Mirzaev, D.A. Sychev
1) Sklifosovsky Research Institute of Emergency Medicine, Moscow, Russia;
2) Russian Medical Academy of Continuous Professional Education, Moscow, Russia;
3) Healthcare Information and Analytical Center, Moscow, Russia
Background. Despite the obvious progress in the diagnosis and treatment of cardiovascular diseases, ST-segment elevation myocardial infarction (STEMI) still occupies a leading position in the structure of mortality and disability in the adult population. Thrombotic complications after percutaneous coronary intervention (PCI) in STEMI may develop despite standard antiplatelet therapy. Genetically determined (GD) causes are one of the main ones. Identification of GD factors in patients with STEMI seems to be important, because may allow timely adjustment of antiplatelet therapy and reduce the likelihood of adverse cardiovascular effects in the perioperative period of PCI.
Objective. Determination of the effect of GD on clinical and laboratory parameters and outcomes in STEMI.
Methods. The study included 46 patients (13 women, 33 men) aged 35 to 83 years, mean age 61.7 years, with STEMI, who underwent PCI in the territory of the infarct-associated artery (IAA). Depending on the presence of GD factors, patients were divided into 2 groups: group I – with the presence of GD factors, group II – with the absence of GD factors. Group I consisted of 21 patients (4 women, 17 men) aged 56.6±2.56 years. Group II consisted of 25 patients (9 women, 16 men) aged 66.0±2.58 years. The study design included laboratory tests (traditional coagulogram, thromboelastometry, aggregometry, pharmacogenetic testing), instrumental studies (ECG, echocardiography) on the 1st, 3rd and 6th days after the patient admission. The following pharmacogenetic markers were determined for all patients: CYP2C19*17, CYP2C19*2, CYP2C19*3, SLCO1B1, CYP3A5*3. The course of the disease and its outcomes were assessed.
Results. There were no intergroup differences in coagulation parameters. The groups did not differ in the severity of coronary injury, according to echocardiography at the time of patient admission and before discharge from the hospital. The duration of hospitalization in group I was 11.1±0.37 days, in group II – 11.0±0.35 days. The duration of stay in the intensive care unit, in the hospital in the groups was the same. A significant relationship was found between the presence of GD factors and the formation of left ventricular (LV) aneurysm, which formed in 19% of patients in group I. In group II, LV aneurysms did not form in any of the cases.
Conclusion. GD factors to P2Y12 receptor antagonists were detected in 46% of patients with STEMI. The presence of GD may be associated with the impossibility of intraoperative achievement of complete restoration of coronary blood flow in the IAA during PCI, as well as with the development of LV aneurysm in the postoperative period.
About the Autors
Corresponding author: Dina S. Markhulia, Anesthesiologist-Resuscitator of the Intensive Care Unit, Sklifosovsky Research Institute of Emergency Medicine, Moscow, Russia; ninidzed@gmail.com
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