Prognostic value of platelet reactivity, inflammatory markersand genotyping in coronary artery disease patientsafter percutaneous coronary intervention
Authors:
Company: A.N. Bakoulev Scientific Center for Cardiovascular Surgery; Rublevskoe shosse, 135, Moscow, 121552, Russian Federation
Keywords: coronary artery stenting platelet aggregation stent thrombosis stent restenosis inflammatory markers PAI-1 von Willebrand factor polymorphism CYP2C19 dual antiplatelet therapy
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2. Widimsky P., Wijns W., Fajadet J. et al. Reperfusion therapy for ST elevation acute myocardial infarction in Europe: description of the current situation in 30 countries. Eur. Heart J. 2010; 31: 943–57.
3. McManus D.D., Gore J., Yarzebski J., Spencer F., Lessard D., Goldberg R.J. Recent trends in the incidence, treatment, and outcomes of patients with STEMI and NSTEMI. Am. J. Med. 2011; 124: 40–7.
4. Montalescot G., White H.D., Gallo R. et al. Enoxaparin versus unfractionated heparin in elective percutaneous coronary intervention. N. Eng. J. Med. 2006; 355: 1006–17.
5. Singh M., Gersh B.J., Lennon R.J. et al. Outcomes of a system-wide protocol for elective and non-elective coronary angioplasty at sites without on-site surgery: the Mayo Clinic experience. Mayo Clin. Proc. 2009; 84: 501–8.
6. Minha S., Pichard A.D., Waksman R. In-stent restenosis of drug-eluting stents. Future Cardiol. 2013; 9: 721–31.
7. Haine S.E., Vrints C.J. Stent thrombosis with drugeluting and bare-metal stents. Lancet. 2012; 380: 646; author reply 646–7.
8. Windecker S., Kolh P., Alfonso F. et al. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur. Heart J. 2014; 35 (37): 2541–619. DOI: 10.1093/eurheartj/ehu278.
9. Breet N.J., van Werkum J.W., Bouman H.J. et al. High on-treatment platelet reactivity to both aspirin and clopidogrel is associated with the highest risk of adverse events following percutaneous coronary intervention. Heart. 2011; 97 (12): 983–90.
10. Stone G.W. A large-scale, prospective, multicenter registry examining the relationship between platelet responsiveness and stent thrombosis after DES implantation. Results from the ADAPT-DES study. J. Am. Coll. Cardiol. 2011; 58 (Suppl. B).
11. Aradi D., Komocsi A., Vorobcsuk A. et al. Prognostic significance of high on- clopidogrel platelet reactivity after percutaneous coronary intervention: Systematic review and meta-analysis. Am. Heart J. 2010; 160: 543–51.
12. Brar S.S., ten Berg J., Marcucci R. et al. Impact of platelet reactivity on clinical outcomes after percu- taneous coronary intervention: A collaborative meta-analysis of individual participant data. J. Am. Coll. Cardiol. 2011; 58: 1945–54.
13. Gong I.Y., Crown N., Suen C.M. et al. Clarifying the importance of CYP2C19 and PON1 in the mechanism of clopidogrel bioactivation and in vivo antiplatelet response. Eur. Heart J. 2012; 33: 2856–464a.
14. Shuldiner A.R., O'Connell J.R., Bliden K.P. et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. J. Am. Med. Assoc. 2009; 302: 849–57.
15. Inoue T., Uchida T., Yaguchi I., Sakai Y., Takayanagi K., Morooka S. Stent-induced expression and activation of the leukocyte integrin Mac-1 is associated with neointimal thickening and restenosis. Circulation. 2003; 107: 1757–63.
16. Gurbel P.A., Bliden K.P., Hiatt B.L., O'Connor C.M. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation. 2003; 107: 2908–13.
17. Park K.W., Jeon K.H., Kang S.H., Oh I.Y., Cho H.J., Lee H.Y. et al. Clinical outcomes of high on-treatment platelet reactivity in Koreans receiving elective percutaneous coronary intervention (from results of the CROSS VERIFY study). Am. J. Cardiol. 2011; 108 (11): 1556–63.
18. Breet N.J., van Werkum J.W., Bouman H.J. et al. Comparison of platelet function tests in predicting clinical outcome in patients undergoing coronary stent implantation. JAMA. 2010; 303: 754–62.
19. Price M.J., Berger P.B., Teirstein P.S. et al. Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA. 2011; 305: 1097–105.
20. Рябинина М.Н. Оптимизация дезагрегантной терапии после стентирования коронарных ар- терий при ИБС: Дис. … канд. мед. наук. М.; 2014: 90–4.
21. Васильева Е.Ю., Касьянова О.В., Шпектор А.В. Уровень С-реактивного белка и эффективность терапии аспирином у пациентов с ишемической болезнью сердца. Кардиология. 2006; 45 (1): 66–7.
22. Park D.W., Lee S.W., Yun S.C., Song H.G., Ahn J.M., Lee J.Y. et al. A point-of-care platelet function assay and C-reactive protein for prediction of major cardiovascular events after drug-eluting stent implantation. J. Am. Coll. Cardiol. 2011; 58 (25): 2630–39.
23. Kaikita K., Ono T., Iwashita S. et al. Impact of CYP2C19 polymorphism on platelet function tests and coagulation and inflammatory biomarkers in patients undergoing percutaneous coronary intervention. J. Atheroscler. Thromb. 2014; 21 (1): 64–76.
24. Церетели Н.В. Влияние длительного приема антиагрегантных препаратов на воспалитель- ный ответ и эндотелиальную функцию у боль- ных ИБС после стентирования коронарных ар- терий: Дис. … канд. мед. наук. М.; 2009: 15–40.
25. Воробьева И.И., Рыжкова Е.В., Васильева Е.Ю., Шпектор А.В. Влияние системного воспаления на эффект антиагрегантной терапии у больных с острым коронарным синдромом. Креативная кардиология. 2012; 1: 5–14.
26. Chen S.L., Liu Y., Lin L. et al. Interleukin-6, but not C-reactive protein, predicts the occurrence of cardiovascular events after drug-eluting stent for unstable angina. J. Interv. Cardiol. 2014; 27 (2): 142–54.
27. Nikolopoulos G.K., Bagos P.G., Tsangaris I. et al. The association between plasminogen activator inhibitor type 1 (PAI-1) levels, PAI-1 4G/5G polymorphism, and myocardial infarction: a Mendelian randomization meta-analysis. Clin. Chem. Lab. Med. 2014; 52 (7): 937–50.
28. Ma Q., Zhou Y., Nie X. et al. Rapamycin affects tissue plasminogen activator and plasminogen activator inhibitor I expression: a potential prothrombotic mechanism of drug-eluting stents. Angiology. 2012; 63 (5): 330–5.
29. Heper G., Murat S.N., Durmaz T., Kalkan F. Prospective evaluation of von Willebrand factor release after multiple and single stenting. Angiology. 2004; 55 (2): 177–86. 30. Jin C., Lu L., Zhu Z.B. et al. Increased serum vWF and sVCAM-1 levels are associated with late or very late angiographic stent thrombosis after sirolimuseluting stent implantation. Coron. Artery Dis. 2010; 21 (5): 273–7.
31. Miyazaki T., Ono T., Matsukawa K. et al. Prognostic value of plasma von Willebrand factor-cleaving (ADAMTS13) and antigen levels in patients with coronary artery disease. Thromb. Haemost. 2010; 103 (3): 623–9.
32. Wallentin L., James S., Storey R.F., Armstrong M., Barratt B.J., Horrow J. et al. Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcome of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a genetic substudy of the PLATO trial. Lancet. 2010; 376: 1320–8.
Abstract
Objective: The aim of our study is to evaluate high on-treatment platelet reactivity and also prognostic impact of various inflammatory markers levels on clinical outcomes based on genetic background of patients after percutaneous coronary intervention. Material and methods. In our study we included 94 patients with stable coronary artery disease during 2009–2013. All patients scheduled to perform percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation were taking dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. To assess the on-treatment platelet response we used the “classical” light trancemittance agregometry with 5 μmol/L ADPand also a new, fully automated method – VerifyNow. In this study we assess baseline levels of different inflammatory markers: level of hs-C-reactive protein (CRP), soluble P-selectin, soluble CD40L, hs-IL-6, level of PAI-1 and von Willebrand factor activity before PCI. All patients were genotyped to define the presence of CYP2C19*2 polymorphism after discharging from hospital. Results. We have found following risk factors for adverse events after PCI with DES implantation: diabetes mellitus, PRU, number of stented arteries, number of implanted stents, the initial level of PAI-1 and von Willebrand factor (vWF) activity. According to the results of our study, it was found that diabetes is an independent predictor of adverse outcomes after PCI [exp(B) 10.299; 95% confidence inteval (CI) 1.236–85.850; p=0.03]. Also PRU (according to the VerifyNow) was found to be an independent predictor of adverse outcome after PCI [exp(B) 1.016; 95% CI, 1.002–1.030; p=0.03]. Significant independent impact was found for the level of PAI-1 and vWF activity before PCI [exp(B) 0.999; 95% CI, 0.999–1.000; p=0.01 and exp(B) 1.000; 95% CI, 1.000–1.000; p=0.045]. Conclusion. Concomitant diabetes mellitus, high platelet reactivity (according to VerifyNow), as well as higher initial level of PAI-1 and von Willebrand factor activity is an independent predictor of adverse cardiac events after PCI with implantation of drug-eluting stents. Light transmittance agregatometry with 5 μmol/L ADP have no significant prognostic impact on clinical outcomes after PCI. Developed predictive models will identify patients with high risk for adverse outcomes after PCI and optimize management of these patients before and after PCI.References
1. The top 10 causes of death. WHO Fact sheet. 2014; 310. Available at: http://www.who.int/mediacentre/ factsheets/fs310/en.2. Widimsky P., Wijns W., Fajadet J. et al. Reperfusion therapy for ST elevation acute myocardial infarction in Europe: description of the current situation in 30 countries. Eur. Heart J. 2010; 31: 943–57.
3. McManus D.D., Gore J., Yarzebski J., Spencer F., Lessard D., Goldberg R.J. Recent trends in the incidence, treatment, and outcomes of patients with STEMI and NSTEMI. Am. J. Med. 2011; 124: 40–7.
4. Montalescot G., White H.D., Gallo R. et al. Enoxaparin versus unfractionated heparin in elective percutaneous coronary intervention. N. Eng. J. Med. 2006; 355: 1006–17.
5. Singh M., Gersh B.J., Lennon R.J. et al. Outcomes of a system-wide protocol for elective and non-elective coronary angioplasty at sites without on-site surgery: the Mayo Clinic experience. Mayo Clin. Proc. 2009; 84: 501–8.
6. Minha S., Pichard A.D., Waksman R. In-stent restenosis of drug-eluting stents. Future Cardiol. 2013; 9: 721–31.
7. Haine S.E., Vrints C.J. Stent thrombosis with drugeluting and bare-metal stents. Lancet. 2012; 380: 646; author reply 646–7.
8. Windecker S., Kolh P., Alfonso F. et al. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur. Heart J. 2014; 35 (37): 2541–619. DOI: 10.1093/eurheartj/ehu278.
9. Breet N.J., van Werkum J.W., Bouman H.J. et al. High on-treatment platelet reactivity to both aspirin and clopidogrel is associated with the highest risk of adverse events following percutaneous coronary intervention. Heart. 2011; 97 (12): 983–90.
10. Stone G.W. A large-scale, prospective, multicenter registry examining the relationship between platelet responsiveness and stent thrombosis after DES implantation. Results from the ADAPT-DES study. J. Am. Coll. Cardiol. 2011; 58 (Suppl. B).
11. Aradi D., Komocsi A., Vorobcsuk A. et al. Prognostic significance of high on- clopidogrel platelet reactivity after percutaneous coronary intervention: Systematic review and meta-analysis. Am. Heart J. 2010; 160: 543–51.
12. Brar S.S., ten Berg J., Marcucci R. et al. Impact of platelet reactivity on clinical outcomes after percu- taneous coronary intervention: A collaborative meta-analysis of individual participant data. J. Am. Coll. Cardiol. 2011; 58: 1945–54.
13. Gong I.Y., Crown N., Suen C.M. et al. Clarifying the importance of CYP2C19 and PON1 in the mechanism of clopidogrel bioactivation and in vivo antiplatelet response. Eur. Heart J. 2012; 33: 2856–464a.
14. Shuldiner A.R., O'Connell J.R., Bliden K.P. et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. J. Am. Med. Assoc. 2009; 302: 849–57.
15. Inoue T., Uchida T., Yaguchi I., Sakai Y., Takayanagi K., Morooka S. Stent-induced expression and activation of the leukocyte integrin Mac-1 is associated with neointimal thickening and restenosis. Circulation. 2003; 107: 1757–63.
16. Gurbel P.A., Bliden K.P., Hiatt B.L., O'Connor C.M. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation. 2003; 107: 2908–13.
17. Park K.W., Jeon K.H., Kang S.H., Oh I.Y., Cho H.J., Lee H.Y. et al. Clinical outcomes of high on-treatment platelet reactivity in Koreans receiving elective percutaneous coronary intervention (from results of the CROSS VERIFY study). Am. J. Cardiol. 2011; 108 (11): 1556–63.
18. Breet N.J., van Werkum J.W., Bouman H.J. et al. Comparison of platelet function tests in predicting clinical outcome in patients undergoing coronary stent implantation. JAMA. 2010; 303: 754–62.
19. Price M.J., Berger P.B., Teirstein P.S. et al. Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA. 2011; 305: 1097–105.
20. Рябинина М.Н. Оптимизация дезагрегантной терапии после стентирования коронарных ар- терий при ИБС: Дис. … канд. мед. наук. М.; 2014: 90–4.
21. Васильева Е.Ю., Касьянова О.В., Шпектор А.В. Уровень С-реактивного белка и эффективность терапии аспирином у пациентов с ишемической болезнью сердца. Кардиология. 2006; 45 (1): 66–7.
22. Park D.W., Lee S.W., Yun S.C., Song H.G., Ahn J.M., Lee J.Y. et al. A point-of-care platelet function assay and C-reactive protein for prediction of major cardiovascular events after drug-eluting stent implantation. J. Am. Coll. Cardiol. 2011; 58 (25): 2630–39.
23. Kaikita K., Ono T., Iwashita S. et al. Impact of CYP2C19 polymorphism on platelet function tests and coagulation and inflammatory biomarkers in patients undergoing percutaneous coronary intervention. J. Atheroscler. Thromb. 2014; 21 (1): 64–76.
24. Церетели Н.В. Влияние длительного приема антиагрегантных препаратов на воспалитель- ный ответ и эндотелиальную функцию у боль- ных ИБС после стентирования коронарных ар- терий: Дис. … канд. мед. наук. М.; 2009: 15–40.
25. Воробьева И.И., Рыжкова Е.В., Васильева Е.Ю., Шпектор А.В. Влияние системного воспаления на эффект антиагрегантной терапии у больных с острым коронарным синдромом. Креативная кардиология. 2012; 1: 5–14.
26. Chen S.L., Liu Y., Lin L. et al. Interleukin-6, but not C-reactive protein, predicts the occurrence of cardiovascular events after drug-eluting stent for unstable angina. J. Interv. Cardiol. 2014; 27 (2): 142–54.
27. Nikolopoulos G.K., Bagos P.G., Tsangaris I. et al. The association between plasminogen activator inhibitor type 1 (PAI-1) levels, PAI-1 4G/5G polymorphism, and myocardial infarction: a Mendelian randomization meta-analysis. Clin. Chem. Lab. Med. 2014; 52 (7): 937–50.
28. Ma Q., Zhou Y., Nie X. et al. Rapamycin affects tissue plasminogen activator and plasminogen activator inhibitor I expression: a potential prothrombotic mechanism of drug-eluting stents. Angiology. 2012; 63 (5): 330–5.
29. Heper G., Murat S.N., Durmaz T., Kalkan F. Prospective evaluation of von Willebrand factor release after multiple and single stenting. Angiology. 2004; 55 (2): 177–86. 30. Jin C., Lu L., Zhu Z.B. et al. Increased serum vWF and sVCAM-1 levels are associated with late or very late angiographic stent thrombosis after sirolimuseluting stent implantation. Coron. Artery Dis. 2010; 21 (5): 273–7.
31. Miyazaki T., Ono T., Matsukawa K. et al. Prognostic value of plasma von Willebrand factor-cleaving (ADAMTS13) and antigen levels in patients with coronary artery disease. Thromb. Haemost. 2010; 103 (3): 623–9.
32. Wallentin L., James S., Storey R.F., Armstrong M., Barratt B.J., Horrow J. et al. Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcome of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a genetic substudy of the PLATO trial. Lancet. 2010; 376: 1320–8.
