The influence of genetic resistance to antiplatelet agents on clinical and laboratory parameters and outcomes in ST-segment elevation myocardial infarction

Capa

Citar

Texto integral

Acesso aberto Acesso aberto
Acesso é fechado Acesso está concedido
Acesso é fechado Acesso é pago ou somente para assinantes

Resumo

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.

Texto integral

Acesso é fechado

Sobre autores

D. Markhulia

Sklifosovsky Research Institute of Emergency Medicine

Autor responsável pela correspondência
Email: ninidzed@gmail.com
ORCID ID: 0000-0002-0064-432X

Anesthesiologist-Resuscitator of the Intensive Care Unit

Rússia, Moscow

K. Popugaev

Sklifosovsky Research Institute of Emergency Medicine

Email: ninidzed@gmail.com
ORCID ID: 0000-0002-6240-820X
Rússia, Moscow

S. Petrikov

Sklifosovsky Research Institute of Emergency Medicine

Email: ninidzed@gmail.com
ORCID ID: 0000-0003-3292-8789
Rússia, Moscow

I. Kuzmina

Sklifosovsky Research Institute of Emergency Medicine

Email: ninidzed@gmail.com
ORCID ID: 0000-0001-9458-7305
Rússia, Moscow

G. Gazaryan

Sklifosovsky Research Institute of Emergency Medicine

Email: ninidzed@gmail.com
ORCID ID: 0000-0001-5090-6212
Rússia, Moscow

K. Kiselev

Healthcare Information and Analytical Center

Email: ninidzed@gmail.com
ORCID ID: 0000-0002-2667-6477
Rússia, Moscow

D. Kosolapov

Sklifosovsky Research Institute of Emergency Medicine

Email: ninidzed@gmail.com
ORCID ID: 0000-0002-6655-1273
Rússia, Moscow

E. Klychnikova

Sklifosovsky Research Institute of Emergency Medicine

Email: ninidzed@gmail.com
ORCID ID: 0000-0002-3349-0451
Rússia, Moscow

M. Godkov

Sklifosovsky Research Institute of Emergency Medicine; Russian Medical Academy of Continuous Professional Education

Email: ninidzed@gmail.com
ORCID ID: 0000-0001-9612-6705
Rússia, Moscow; Moscow

M. Parkhomenko

Sklifosovsky Research Institute of Emergency Medicine

Email: ninidzed@gmail.com
ORCID ID: 0000-0001-5408-6880
Rússia, Moscow

A. Kramarenko

Sklifosovsky Research Institute of Emergency Medicine

Email: ninidzed@gmail.com
ORCID ID: 0000-0003-2039-5604
Rússia, Moscow

S. Golovanev

Sklifosovsky Research Institute of Emergency Medicine

Email: ninidzed@gmail.com
Rússia, Moscow

K. Mirzaev

Russian Medical Academy of Continuous Professional Education

Email: ninidzed@gmail.com
ORCID ID: 0000-0002-9307-4994
Rússia, Moscow

D. Sychev

Russian Medical Academy of Continuous Professional Education

Email: ninidzed@gmail.com
ORCID ID: 0000-0002-4496-3680
Rússia, Moscow

Bibliografia

  1. Староверов И.И., Шахнович Р.М., Гиляров М.Ю. и др. Евразийские клинические рекомендации по диагностике и лечению острого коронарного синдрома с подъемом сегмента ST (ОКСпST). Евразийский кардиологический журнал. 2020;(1):4–77. [Staroverov I.I., Shakhnovich R.M., Gilyarov M.Yu., et al. Eurasian clinical guidelines on diagnosis and treatment of acute coronary syndrome with ST segment elevation (STEMI). Evraz Kardiol J. 2020;(1):4–77. (In Russ.)]. doi: 10.38109/2225-1685-2020-1-4-77.
  2. Ibanez B., James S., Agewall S., et al. ESC Scientific Document Group, 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018;39(2):119–77. doi: 10.1093/eurheartj/ ehx393.
  3. Wiviott S.D., Steg P.G. Clinical evidence for oral antiplatelet therapy in acute coronary syndromes. Lancet. 2015;386(9990):292–302. doi: 10.1016/S0140-6736(15)60213-6.
  4. Острый инфаркт миокарда с подъемом сегмента ST электрокардиограммы. Клинические рекомендации 2020. М., 2020. [2020 Clinical practice guidelines for Acute ST-segment elevation myocardial infarction. M., 2020. (In Russ.)].
  5. Полтавская М.Г., Меситская Д.Ф., Новикова А.И., Плаксина Н.А. Преимущества комбинации клопидогрела и аспирина у больных с высоким сердечно-сосудистым риском. Кардиология и сердечно-сосудистая хирургия. 2019;12(6):504 9. [Poltavskaya M.G., Mesitskaia D.F., Novikova A.I., Plaksina N.A. Benefits of a combination of clopidogrel and aspirin in patients with high cardiovascular risk. Kardiol Serdechno-sosud Khirurg. 2019;12(6):504–9. (In Russ.)]. doi: 10.17116/kardio201912061504.
  6. Montrief T., Davis W.T., Koyfman A., Long B. Mechanical, inflammatory, and embolic complications of myocardial infarction: An emergency medicine review. Am J Emerg Med. 2019;37(6):1175–83. doi: 10.1016/j.ajem.2019.04.003.
  7. Pandey C.P., Misra A., Negi M.P.S., et al. Aspirin & clopidogrel non-responsiveness & its association with genetic polymorphisms in patients with myocardial infarction. Indian J Med Res. 2019;150(1):50–61. doi: 10.4103/ijmr.IJMR_782_17.
  8. Бокарев И.Н., Попова Л.В. Резистентность к антитромбоцитарным препаратам. Сердце: журнал для практикующих врачей. 2012;11(2):103–7. [Bokarev I.N., Popova L.V. Resistance to antiplatelet drugs. Serdtse: zhurnal dlya praktikuyushchikh vrachey. 2012;11(2):103–7. (In Russ.)].
  9. Lee C.R., Luzum J.A., Sangkuhl K., et al. Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 Genotype and Clopidogrel Therapy: 2022 Update. Clin Pharmacol Ther. 2022;112(5):959–67. doi: 10.1002/cpt.2526.
  10. Сычев Д.А., Торбенков Е.С. Клиническая фармакогенетика антиагреганта тикагрелора: есть ли перспективы? Фармакогенетика и фармакогеномика. 2016;(2):24–6. [Sychev D.A., Torbenkov E.S. Clinical pharmacogenetics of ticagrelor: is there prospect? Farmakogenet Farmakogenom. 2016;(2):24–6. (In Russ.)].
  11. Ranucci M., Baryshnikova E. Sensitivity of Viscoelastic Tests to Platelet Function. J Clin Med. 2020;9(1):189. doi: 10.3390/jcm9010189.
  12. Akay O.M. The Double Hazard of Bleeding and Thrombosis in Hemostasis from a Clinical Point of View: A Global Assessment by Rotational Thromboelastometry (ROTEM). Clin Appl Thromb Hemost. 2018;24(6):850–58. doi: 10.1177/1076029618772336.
  13. Bhardwaj V., Kapoor P.M. Platelet aggregometry interpretation using ROTEM – PART-II. Ann Card Anaesth. 2016;19(4):584–86. doi: 10.4103/0971-9784.191559.
  14. Michelson A.D. Methods for the Measurement of Platelet Function. Am J Cardiol. 2009;103(Suppl. 3):20A–6. doi: 10.1016/j.amjcard.2008.11.019.
  15. Born G.V. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature. 1962;194:927–29. doi: 10.1038/194927b0.
  16. Aitmokhtar O., Paganelli F., Benamara S., et al. Impact of platelet inhibition level on subsequent no-reflow in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Arch Cardiovasc Dis. 2017;110(11):626–33. doi: 10.1016/j.acvd.2016.12.017.
  17. Komosa A., Lesiak M., Siniawski A., et al. Significance of antiplatelet therapy in emergency myocardial infarction treatment. Postepy Kardiol Interwencyjnej. 2014;10(1):32–9. doi: 10.5114/pwki.2014.41466.
  18. Michelson A.D., Frelinger A.L., Furman M.I. Resistance to antiplatelet drugs. Eur Heart J Suppl. 2006;8(Suppl. G):G53–8. doi: 10.1093/eurheartj/sul056.
  19. Michelson A.D. Platelet Function Testing in Cardiovascular Diseases. Circulation. 2004;110(19):e489–93. doi: 10.1161/01.CIR.0000147228.29325.F9.
  20. Sheng X.Y., An H.J., He Y.Y., et al. High-Dose Clopidogrel versus Ticagrelor in CYP2C19 intermediate or poor metabolizers after percutaneous coronary intervention: A Meta-Analysis of Randomized Trials. J Clin Pharm Ther. 2022;47(8):1112–21. doi: 10.1111/jcpt.13665.
  21. Xie Q., Xiang Q., Liu Z., et al. Effect of CYP2C19 genetic polymorphism on the pharmacodynamics and clinical outcomes for patients treated with ticagrelor: a systematic review with qualitative and quantitative meta-analysis. BMC. Cardiovasc Disord. 2022;22(1):111. Foi: 10.1186/s12872-022-02547-3.
  22. Li-Wan-Po A., Girard T., Farndon P., et al. Pharmacogenetics of CYP2C19: functional and clinical implications of a new variant CYP2C19*17. Br J Clin Pharmacol. 2010;69(3):222–30. doi: 10.1111/j.1365-2125.2009.03578.x.
  23. Liu S., Shi X., Tian X., et al. Effect of CYP3A4*1G and CYP3A5*3 Polymorphisms on Pharmacokinetics and Pharmacodynamics of Ticagrelor in Healthy Chinese Subjects. Front Pharmacol. 2017;8:176. doi: 10.3389/fphar.2017.00176 eCollection 2017.
  24. Ramsey L.B., Gong L., Lee S.B., et al. PharmVar GeneFocus: SLCO1B1. Clin Pharmacol Ther. 2023;113(4):782–93. doi: 10.1002/cpt.2705.
  25. Ferreira M., Freitas-Silva M., Assis J., et al. The emergent phenomenon of aspirin resistance: insights from genetic association studies. Pharmacogenomics. 2020;21(2):125–40. doi: 10.2217/pgs-2019-0133.
  26. van Veen J.J., Spahn D.R., Makris M. Routine preoperative coagulation tests: an outdated practice? Br J Anaesth. 2011;106(1):1–3. doi: 10.1093/bja/aeq357.
  27. Hvas A.M., Favaloro E.J. Platelet Function Analyzed by Light Transmission Aggregometry. Methods Mol Biol. 2017;1646:321–31. doi: 10.1007/978-1-4939-7196-1_25.
  28. Spalding G.J., Hartrumpf M., Sierig T., et al. Cost reduction of perioperative coagulation management in cardiac surgery: value of ‘bedside’ thrombelastography (ROTEM). Eur J Cardiothorac Surg. 2007;31(6):1052–57. doi: 10.1016/j.ejcts.2007.02.022.
  29. Whiting D., DiNardo J.A. TEG and ROTEM: Technology and clinical applications. Am J Hematol. 2014;89(2):228–32. doi: 10.1002/ajh.23599.
  30. Тишкина И.Е., Переверзева К.Г., Якушин С.С. Предикторы формирования постинфарктной аневризмы левого желудочка. Российский кардиологический журнал. 2023;28(2):118–24. [Tishkina I.E., Pereverzeva K.G., Yakushin S.S. Predictors of post-infarction left ventricular aneurysm. Ros Kardiol J. 2023;28(2):118–24. (In Russ.)]. doi: 10.15829/1560-4071-2023-5201.
  31. Rezkalla S.H., Kloner R.A. No-Reflow Phenomenon. Circulation. 2002;105(5):656–62. doi: 10.1161/hc0502.102867.

Arquivos suplementares

Arquivos suplementares
Ação
1. JATS XML
2. Fig. Study design

Baixar (111KB)

Declaração de direitos autorais © Bionika Media, 2023

Este site utiliza cookies

Ao continuar usando nosso site, você concorda com o procedimento de cookies que mantêm o site funcionando normalmente.

Informação sobre cookies