Prospective multicenter observational the personalized therapy with clopidogrel for stenting in acute coronary syndrome regarding the genetic polymorphisms (PROTOCOL) study

Clopidogrel remains the main antiplatelet therapy drug for patients after coronary stenting (CS) due to acute coronary syndrome (ACS). The paper contains substantiation and design of an observatory study with the purpose to test the hypothesis that high frequency of of cytochrome CYP2d9*2 polymorphism is associated with coronary stent thrombosis and with paradoxical response to clopidogrel in Siberian residents after CS due to ACS. Response to clopidogrel will be registered by means of light transmission aggregometry (turbidity method) in presence of adenosine diphosphate. Over the period of 30 days after coronary stenting, patients receiving clopidogrel will undergo 4 visits to assess antiplatelet therapy efficacy (end point - early stent thrombosis) and safety (all bleeding events), with consideration of genetic profile. Ethic support of the study

клопидогрел, стентирование коронарных сосудов, острый коронарный синдром, персонализированная терапия, световая трансмиссионная агрегометрии, резистентность к клопидогрелу, парадоксальный ответ, генетические полиморфизмы, обсервационное исследование, наблюдательное исследование, clopidogrel, coronary stenting, acute coronary syndrome, personalized therapy, light transmission aggregometry, clopidogrel resistance, paradoxical response, genetic polymorphisms, observasional study

1. The CURRENT-OASIS 7 Investigators. Dose Comparisons of Clopidogrel and Aspirin in Acute Coronary Syndromes. // N Engl J Med 2010, 363 (10): 930-42.

2. Matthew J., Price M.J., Berger P.B., Teirstein P.S., Tanguay J.-F., Angiolillo D.J. et al. for the GRAVITAS Investigator. Standard- vs High-Dose Clopidogrel Based on Platelet Function Testing After Percutaneous Coronary Intervention. The GRAVITAS Randomized Trial. // JAMA 2011, 305(11): 1097-104.

3. Dewilde W.J.M., Oirbans T., Verheugt F.W.A., Kelder J.C., De Smet B.J.G.L., Herrman J-P. et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. // Lancet 2013, 381(9872): 1107-15.

4. Aradi D., Storey R.F., Komocsi A., Trenk D., Gulba D., Kiss R.G. et al. on behalf of the Working Group on Thrombosis of the European Society of Cardiology Expert position paper on the role of platelet function testing in patients undergoing percutaneous coronary intervention. // Eur Heart J 2014, 35(4): 209-15.

5. Mega J.L., Simon T., Collet J.P., Anderson J.L., Antman E.M., Bliden K. et al. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. // JAMA 2010, 304(16): 1821-30.

6. Harmsze A.M., van Werkum J. W., ten Berg J.M., Zwart B., Bouman H.J., Breet N.J. et al. CYP2C19*2 and CYP2C9*3 alleles are associated with stent thrombosis: a case-control study. // Eur Heart J 2010, 31(24): 3046.

7. Sibbing D., Stegherr J., Latz W., Koch W., Mehilli J., D?rrler K. et al. Cytochrome P450 2C19 loss-of-function polymorphism and stent thrombosis following percutaneous coronary intervention. // Eur Heart J 2009, 30(8): 916-22.

8. Robertson D., Williams G.H. Clinical and translational Science: Principles of Human Research. 1st ed. Academic Press: Elsevier; 2009.

9. Лифшиц Г.И., Данилкина С.Т., Гуськова Е.В., Воронина Е.Н., Филипенко М.Л. Ассоциация генов, кодирующих белки гемостаза, с параметрами периферического гемостаза и предрасположенностью к атеротромбозам у пациентов с сердечно-сосудистыми заболеваниями. // Кардиоваскулярная терапия и профилактика 2011, 4: 90-6.

10. Price M.P., Murray S.S., Angiolillo D.J., Lillie E., Smith E.N., Tisch R.L. et al. Influence of Genetic Polymorphisms on the Effect of High- and Standard-Dose Clopidogrel After Percutaneous Coronary Intervention. // J Am Col Cardiol 2012, 59 (22): 1928-37.

11. Aradi D., Sibbing D., Bonello L. Current evidence for monitoring platelet reactivity in acute coronary syndrome: A plea for individualized antiplatelet treatment. // Int J Cardiol 2013, 167 (5): 1794-97.

12. Orban M., Sibbing D. Platelet Function Testing in Patients with Acute Coronary Syndrome // J Cardiovascular Translational Research 2013, 6 (3): 371-7.

13. Грацианский Н.А. Некоторые методы оценки функции тромбоцитов при лечении клопилогрелем и связь их результатов с ишемическими событиями и кровотечениями - [Электронный ресурс]. - Режим доступа http://athero.ru/Genes.pdf. - 23 ноября 2013 г.

14. Gremmel T., Steiner S., Seidinger D., Koppensteiner R., Panzer S., Kopp C.W. Comparison of methods to evaluate clopidogrel-mediated platelet inhibition after percutaneous intervention with stent implantation. // Thromb Haemost 2009, 101 (2): 333-9.

15. Клиническая лабораторная диагностика: Национальное руководство: в 2 т. - Т. 1. / под ред. В.В. Долгова, В.В. Меньшикова. М.: ГЭОТАР-Медиа, 2012: 761-4.

16. Айнетдинова Д.Х., Удовиченко А.Е., Сулимов В.А. Резистентность к антитромбоцитарным препаратам у больных острым коронарным синдромом с подьёмом сегмента ST. // Рациональная фармакотерапия в кардиологии 2008, 2: 23-9.

17. Кнауэр Н.Ю., Лифшиц Г.И., Воронина Е.Н., Коледа И.В., Гуськова Е.В. Информативность генетических маркеров для оптимизации персонализированной терапии клопидогрелем. // Кардиология 2013, 8: 72-5.

18. Joshi R., Hossain R., Morton A.C., Ecob R., Judge H.M., Wales C. et al. Evolving pattern of platelet P2Y12 inhibition in patients with acute coronary syndromes // Platelets 2014, 25 (6): 416- 22.

19. Lua D., Owens J., Kreutz R.P. Plasma and whole blood clot strength measured by thrombelastography in patients treated with clopidogrel during acute coronary syndromes. // Thromb Res 2013, 132 (2): 94-8.

20. Tsantes A.E., Ikonomidis I., Papadakis I., Bonovas S., Gialeraki A., Kottaridi C. et al. Impact of the proton pump inhibitors and CYP2C19*2 polymorphism on platelet response to clopidogrel as assessed by four platelet function assays. // Thromb Res 2013, 132 (2): 105-11.

21. Angiolio D.J., Saucedo J.F., DeRaad R., Frelinger A.L., Gurbel P.A., Costigan T.M. et al. Increased platelet inhibition after switching from maintenance clopidogrel to prasugrel in patients with acute coronary syndromes. Results of the SWAP (Switching Anti Platelet) study. // J Am Coll Cardiol 2010, 56 (13): 1017-23.

22. Rideg O., Komocsi A., Magyarlaki T., Tokés-Füzesi M., Miseta A., Kovács G.L. et al. Impact of genetic variants on post-clopidogrel platelet reactivity in patients after elective percutaneous coronary intervention. // Pharmacogenomics 2011, 12 (9): 1269-80.

23. Buonamici P., Marcucci R., Migliorini A., Gensini G.F., Santini A., Paniccia R. et al. Impact of platelet reactivity after clopidogrel administration on drug-eluting stent thrombosis. // J Am Coll Cardiol 2007, 49 (24): 2312-17.

24. Mejin M., Tiong W.N., Hui Lai L.Y., Tiong L.L., Bujang A.M., Hwang S.S. et al. CYP2C19 genotypes and their impact on clopidogrel responsiveness in percutaneous coronary intervention. // Int J Clin Pharm 2013, 35 (4): 621-8.

25. Belozertseva L.A., Voronina E.N., Kokh N.V., Tsvetovskaya G.A., Momot A.P., Lifshits G.I. et al. Personalized approach of medication by indirect anticoagulants tailored to the patient-Russian context: what are the prospects? // EPMA J 2012, 3 (1): 10.

26. Лифшиц Г.И., Отева Э.А., Николаев К.Ю., Куроедов А.Ю., Николаева А.А., Масленников А.Б. Особенности формирования факторов риска ишеми ческой болезни сердца у детей с отягощённым семейным анамнезом и подходы к профилактике. // Консилиум 1999,6:60-63

27. Samama C.M., Lecoules N., Kierzek G., Claessens Y.E., Riou B., Rosencher N. et al. FONDACAST Study Group. Comparison of fondaparinux with low molecular weight heparin for venous thromboembolism prevention in patients requiring rigid or semi-rigid immobilization for isolated non-surgical below-knee injury. // J Thromb Haemost 2013, 11 (10): 1833-43.

28. Breet N.J., van Werkum J.W., Bouman H.J., Ten Berg J.M., Hackeng C.M. et al. Platelet function tests for the monitoring of P2Y12 inhibitors. // Expert Opin Med Diagn 2010, 4(3):251-65.

29. Маниатис Т., Фрич Э. и Сэмбрук Дж. 1984. Молекулярное клонирование. М.: Мир.

30. http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4253b1_01.pdf

31. Bovill E.G., Terrin M.L., Stump D.C., Berke A.D., Frederick M., Collen D., et al. Hemorrhagic events during therapy with recombinant tissue-type plasminogen activator, heparin, and aspirin for acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI), Phase II Trial. // Ann Intern Med 1991, 115 (4): 256-65.

32. Mega J.L., Close S.L., Wiviott S.D., Shen L., Hockett R.D., Brandt J. T. et al. Cytochrome P-450 polymorphisms and response to clopidogrel. // Engl J Med. 2009; 360(4): 354-62.

33. CC/AHA/SCAI 2005 GUIDELINE UPDATE FOR PERCUTANEOUS CORONARY INTERVENTION A Report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention). // J Am Coll Cardiol 2006, 47: 1-121.

34. Вольская Е., Александрова О. Новый статус для наблюдательных исследований // Ремедиум 2009, 3: 6-10.

35. Вольская Е.А. Основы надлежащей практики неинтервенционных исследований лекарственных препаратов. // Качественная клиническая практика 2011, 1: 19-24.

36. von Elm E., Altmanc D.G., Egger M., Pocock S.J., Gotzschee P.C., Vandenbrouckef J.P. for the STROBE The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. // Journal of Clinical Epidemiology 2008, 61: 344-9.