Rational Pharmacotherapy in Cardiology

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Aim. To study the effect of replacing clopidogrel with ticagrelor on endpoints of hospital period and one year after ST Segment Elevation Myocardial Infarction (STEMI).

Material and methods. The study enrolled 80 patients with STEMI. At the stage  of emergency medical service, all patients received loading doses of acetylsalicylic acid (250 mg) and clopidogrel (600 mg). After 12-24 hours,  the patients were randomized into two groups. Patients of the first group received maintenance doses of acetylsalicylic acid (100 mg/day) and clopidogrel 75 mg/day. Patients of the second  group received maintenance doses of acetylsalicylic acid (100 mg/day) and ticagrelor 90 mg twice a day. ADP-induced platelet aggregation (1.25 and 2.5 mg/ml) and proinflammatory factors blood levels (C-reactive protein [CRP], interleukin 6 [IL-6]) were investigated before clopidogrel replacement, as well as 2 hours and 7 days after its replacement. Endpoints were recorded at the patient's discharge and one year later.

Results. After a year in the ticagrelor group there was a trend towards fewer endpoints compared to clopidogrel group (combined endpoint 14.2% vs

25%, p=0.14). In the ticagrelor group, there was no significant increase in the incidence of bleeding compared with the clopidogrel group both in the hospital period and during the year after the STEMI (large bleeding – 0 vs 3.3%, small bleeding – 25.4% vs 26.6%, p=0.48). On the 8th day of STEMI (7 days after clopidogrel replacement), platelet aggregation in the clopidogrel group was significantly higher compared to platelet aggregation in the ticagrelor group (p=0.00). The level of CRP and IL-6 on the 8th day of hospitalization in the clopidogrel group was significantly higher in comparison with the ticagrelor group (p=0.04 and p=0.01, respectively).

Conclusion. When clopidogrel is replaced with ticagrelor on the 1st day of STEMI, there is a tendency to a lower incidence of endpoints during the first year of follow-up. Such switching is safe from the point of view of hemorrhagic complications and is associated with lower platelet aggregation and inflammation activity estimated 7 days after clopidogrel replacement (on the 8th day of STEMI).

About the Authors

E. V. Tavlueva
Research Institute for Complex Issues of Cardiovascular Diseases
Russian Federation

Evgeniya V. Tavlueva – MD, PhD, Leading Researcher,  Laboratory of Pathophysiology of Multifocal Atherosclerosis.

Sosnoviy bulvar 6, Kemerovo, 650002

A. V. Alekseenko
Research Institute for Complex Issues of Cardiovascular Diseases
Russian Federation

Alexey Alekseenko – MD, Post-Graduate Student.

Sosnoviy bulvar 6, Kemerovo, 650002

O. V. Gruzdeva
Research Institute for Complex Issues of Cardiovascular Diseases
Russian Federation

Olga V. Gruzdeva – MD, PhD, Head of Laboratory of Homeostasis Research.

Sosnoviy bulvar 6, Kemerovo, 650002

O. L. Barbarash
Research Institute for Complex Issues of Cardiovascular Diseases
Russian Federation

Olga L. Barbarash – MD, PhD, Professor, Corresponding Member of the Russian Academy of Sciences, Director.

Sosnoviy bulvar 6, Kemerovo, 650002


1. Li Zh., Li Y., Zhang T. et al. Comparison of the influence of ticagrelor and clopidogrel on inflammatory biomarkers and vascular endothelial function for patients with ST-segment elevation myocardial infarction receiving emergency percutaneous coronary intervention: study protocol for a randomized controlled trial. Trials. 2016;17:75. doi: 10.1186/s13063-016-1168-9.

2. Tavlueva E.V., Yarkovskaya A.P., Alekseenko A.V. et al. Hypoaggregatory effect in patients with ST segment elevation myocardial infarction when replacing clopidogrel with ticagrelor. Aterotromboz. 2016;2:54-60. (In Russ.) [Тавлуева Е.В., Ярковская А.П., Алексеенко А.В. и др. Гипоагрегационный эффект у больных инфарктом миокарда с подъемом сегмента ST при замене клопидогрела на тикагрелор. Атеротромбоз. 2016;2:54-60]. doi: 10.21518/2307-1109-2016-2-54-60.

3. 2014 AHA/ACC Guidelines for the management of patients with non-ST-elevation acute coronary syndrome: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines. Circulation. 2014;130: e344-e426. doi: 10.1161/CIR.0000000000000134.

4. Yusuf S., Zhao F., Mehta S.R., et al. Clopidogrel in unstable angina to prevent recurrent events (СURE) trial investigators. Effect of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494-502. doi:10.1056/NEJMoa010746.

5. Wallentin L., Becker R.C., Budaj A. et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361:1045-57. doi: 10.1056/NEJMoa0904327.

6. Varenhorst C., Alstrem U., E Braun O. et al. Causes of mortaliti with ticagrelor compared with clopidogrel in acute coronary syndromes. Heart. 2014;100(22):1762-69. doi: 10.1136/heartjnl-2014-305619.

7. Bonaca M.P., Bhatt D.L., Cohen M. et al. For the PEGASUS-TIMI 54 steering committee and investigators. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;372:1791-1800. doi: 10.1056/NEJMoa1500857.

8. Nechaeva G.I., Drokina O.V., Fisun N.N. Modern antiplatelet therapy: the place of ticagrelor in clinical recommendations. Lechashhij Vrach. 2015;3:72-5. (In Russ.) [Нечаева Г.И., Дрокина О.В., Фисун Н.Н. Cовременная антиагрегантная терапия: место тикагрелора в клинических рекомендациях. Лечащий Врач. 2015;3:72-5].

9. Markov V.A., Vyshlov E.V. Thrombolytic therapy with myocardial infarction. Tomsk: STT; 2011. (In Russ.) [Марков В.А., Вышлов Е.В. Тромболитическая терапия при инфаркте миокарда. Томск: STT; 2011].

10. Averkov O.V. Dual antilatelet therapy as a long-term intervention in the framework of secondary prevention after myocardial infarction: focus on ticagrelor. Conilium medicum 2015;5(17):38-43. (In Russ.) [Аверков О.В. Двойная антитроимбоцитарная терапия как долгосрочное вмешательство в рамках вторичной профилактики после инфаркта миокарда: фокус на тикагрелор. Conilium Medicum. 2015;5(17):38-43].

11. Lindholm D., Varenhorst C., Cannon C.P. et al. Ticagrelor versus clopidogrel in patient with non-ST-elevation acute coronary syndrome with or without revascularization: results from the PLATO trial. Eur Heart J. 2014;35:2083-93. doi: 10.1093/eurheartj/ehu160.

12. Pleskanovskaja S.A., Tachmuhammedova A. H. Influence of the decoction of MT on the population composition of leukocytes, the number and morphology of peripheral blood platelets of conventionally healthy individuals are in vitro. Molodoj Uchenyj. 2015;12:86-91. (In Russ.) [Плескановская С. А., Тачмухаммедова А. Х. Влияние отвара МТ на популяционный состав лейкоцитов, численность и морфологию тромбоцитов периферической крови условно здоровых лиц in vitro. Молодой Ученый. 2015;12:86-91].

13. Storey R.F., Angiolillo D.J., Patil S.B. et al. Inhibitory effects of ticagrelor compared with clopidogrel on platelet function in patients with acute coronary syndromes. The PLATO (PLATelet inhibition and patient Outcomes) PLATELET Substudy. J Am Coll Cardiol. 2010;56(18):1456-62. doi: 10.1016/j.jacc.2010.03.100.

14. DiNicolantonio J.J., Tomek A. Inactivations, deletions, non-adjudications, and downgrades of clinical endpoints on ticagrelor: Serious concerns over the reliability of the PLATO trial. Int J Cardiol. 2013;168:4076-80. doi: 10.1016/j.ijcard.2013.07.020.

15. Stone G.W. Ticagrelor in ACS: redefining a new standart of care? Lancet. 2010;375(9711):263-66. doi: 10.1016/S0140-6736(10)60070-0.

16. Sunitha S., Rajappa M, Mohan Thappa D. et al. Is the ratio of antibodies against oxidized LDL to oxidized LDL an indicator of cardiovascular risk in psoriasis? Oman Med J. 2016;31(5):390-93. doi: 10.5001/omj.2016.78.

17. Widén C., Holmer H., Coleman M. et al. Systemic inflammatory impact of periodontitis on acute coronary syndrome. J Clin Periodontol. 2016;43(9):713-19. doi: 10.1111/jcpe.12540.

18. Oh S.J., Na Kim E., Jai Kim C. et al. The effect of C-reactive protein deposition on myocardium with ischaemia-reperfusion injury in rats. Interact Cardiovasc Thorac Surg. 2017 May 5. doi: 10.1093/icvts/ivx107. [Epub ahead of print]

19. Guo F.M., Han X.H., Guo Y.Y. et al. Correlation study between interleukin-6 levels and coronary reflow. Eur Rev Med Pharmacol Sci. 2017;21(8):1837-42.

20. Ridker P.M., Cushman M., Stampfer M.J. et al. Plasma concentration of C-reactive protein and risk of developing peripheral vascular disease. Circulation. 1998;97:425-28.

21. Kiris I., Kapan S., Narin C. et al. Relationship between site of myocardial infarction, left ventricular function and cytokine levels in patients undergoing coronary artery surgery. Cardiovasc J Afr. 2016;27(5):299-306. doi: 10.5830/CVJA-2016-027.

22. Bester J., Pretorius E. Effects of IL-1β, IL-6 and IL-8 on erythrocytes, platelets and clot viscoelasticity. Sci Rep. 2016;6:32188. doi: 10.1038/srep32188.

23. Thomas M.R., Outteridge S.N., Ajjan R.A. et al. Platelet P2Y12 inhibitors reduce systemic inflammation and its prothrombotic effects in an experimental human model. Arterioscler Thromb Vasc Biol. 2015;35(12):2562-70. doi: 10.1161/ATVBAHA.115.306528.

For citation:

Tavlueva E.V., Alekseenko A.V., Gruzdeva O.V., Barbarash O.L. INFLUENCE OF SWITCHING OF CLOPIDOGREL TO TICAGRELOR ON THE DEVELOPMENT OF CARDIOVASCULAR EVENTS IN PATIENTS WITH ST SEGMENT ELEVATION. Rational Pharmacotherapy in Cardiology. 2017;13(5):590-596. (In Russ.)

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