Modern antithrombotic treatment after ACS – do we use it adequately?

Czech version

Authors: J. Špinar ¹; J. Vítovec ²
Authors‘ workplace: Interní kardiologická klinika LF MU a FN Brno, Brno ¹; I. interní kardioangiologická klinika LF MU a FN u sv. Anny v Brně ²
Published in: Kardiol Rev Int Med 2017, 19(1): 56-60

Overview

Ticagrelor is an adenosine derivate and it is an oral, reversible, direct inhibitor of adenosine diphosphate (ADP) receptor type P2Y₁₂ with a rapid effect and higher anti-aggregation activity than clopidogrel. Ticagrelor (180mg loading dose, 90mg twice daily long term) was tested against clopidogrel (300–600mg loading dose, 75mg long term) in the PLATO study in 18,624 patients after acute coronary syndrome with or without ST elevation. The combined endpoint defined as death, myocardial infarction or stroke was observed in 9.8% of subjects in the Ticagrelor group and in 11.7% in the clopidogrel group after 12 months (p < 0.001). There was no difference in bleeding (11.6 vs. 11.2%, p = 0.43). Ticagrelor decreased significantly the primary endpoint from 22.0 to 17.3% in patients with chronic kidney disease (creatinine clearance less than 60 ml/min, n = 3.237) with more significant decrease of the absolute risk when compared to the whole population (7.9 vs. 8.9%). The PEGASUS-TIMI 54 tested the long-term effect of Ticagrelor after myocardial infarction and showed a decrease of the risk of death after myocardial infarction and stroke with a small increase in bleeding.

Keywords:
ticagrelor – myocardial infarction – anti-aggregation – renal functions

Sources

1. Bultas J. Ticagrelor. Remedia 2011; 21(2): 116– 125.

2. Špinar J, Vítovec J. Ticagrelor a studie PLATO. Kardiol Rev 2012; 13(4): 254– 257.

3. Špinar J. Význam studie Pegasus a nová indikace ticagreloru. Farmakoterapie 2016; 4: 10– 13.

4. Penka M. Máme dnes lepší antitrombotika? Kardiol Rev 2012; 14(2): 62.

5. Penka M. Antikoagulační a antiagregační léčba – základní principy. Kardiol Rev 2012; 14(2): 63– 67.

6. Scirica BM, Cannon CP, Emanuelsson H et al. The incidence of bradyarrhythmias and clinical bradyarrhythmic events in patients with acute coronary syndromes treated with ticagrelor or clopidogrel in the PLATO (Platelet Inhibition and Patient Outcomes) trial: results of the continuous electrocardiographic assessment substudy. J Am Coll Cardiol 2011; 57(19): 1908– 1916. doi: 10.1016/ j.jacc.2010.11.056.

7. Wallentin L, Becker RC, Budaj A et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361(11): 1045– 1057. doi: 10.1056/ NEJMoa0904327.

8. Amsterdam EA, Wenger NK, Brindis RG et al. 2014 AHA/ ACC guideline for the management of patients with non-st-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines. Circulation 2014; 130(25): 2354– 2394. doi: 10.1161/ CIR.0000000000000133.

9. Hamm CW, Bassand JP, Agewall S et al. ESC Guide-lines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2011; 32(23): 2999– 3054. doi: 10.1093/ eurheartj/ ehr236.

10. O'Gara PT, Kushner FG, Ascheim DD et al. 2013 ACCF/ AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guide-lines. Circulation 2013; 127(4): e362– e425. doi: 10.1161/ CIR.0b013e3182742cf6.

11. Montalescot G, Sechtem U, Achenbach S et al. Task Force Members. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J 2013; 34(38): 2949– 3003. doi: 10.1093/ eurheartj/ eht296.

12. Steg PG, James SK, Atar D et al. Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012; 33(20): 2569– 2619. doi: 10.1093/ eurheartj/ ehs215.

13. James S, Budaj A, Aylward P et al. Ticagrelor versus clopidogrel in acute coronary syndromes in relation to renal function. results from the Platelet Inhibition and Patient Outcomes (PLATO) trial. Circulation 2010; 122(11): 1056– 1067. doi: 10.1161/ CIRCULATIONAHA.109.933796.

14. Bonaca MP, Bhatt DL, Cohen M et al. 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(19): 1791– 1800. doi: 10.1056/ NEJMoa1500857.

15. Bonaca MP, Bhatt DL, Oude Ophuis T et al. Long-term tolerability of ticagrelor for secondary prevention of major adverse cardiovascular events: a secondary analysis of the PEGASUS-TIMI 54 trial. JAMA Cardiol 2016; 1(4): 425– 432. doi: 10.1001/ jamacardio.2016.1017.

16. Špinar J, Špinarová L, Vítovec J. Studie PEGASUS – duální antiagregace (ASA + ticagrelor) dlouhodobě po infarktu myokardu. Kardiol Rev Int Med 2015; 17(1): 41– 45.

17. Špinar J, Špinarová L, Vítovec J. Ticagrelor a duální antiagregace po infarktu myokardu – studie PEGASUS. Farmakoterapie 2015; 1: 74– 80.

18. Bonaca MP, Bhatt DL, Braunwald E et al. Design and rationale for the prevention of cardiovascular events in patients with prior heart attack using ticagrelor compared to placebo on a background of aspirin-thrombolysis in myocardial infarction 54 (PEGASUS-TIMI 54) trial. Am Heart J 2014; 167(4): 437– 444.e5. doi: 10.1016/ j.ahj.2013.12.020.

19. Mehran R, Rao SV, Bhatt DL et al. Standardized bleeding definitions for cardiovascular clinical trial. a consensus report from the bleeding academic research consortium. Circulation 2011; 123(23): 2736– 2747. doi: 10.1161/ CIRCULATIONAHA.110.009449.

20. Fihn SD, Gardin JM, Abrams J et al. 2012 ACCF/ AHA/ ACP/ AATS/ PCNA/ SCAI/ STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/ American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation 2012; 126(25): e354– e471. doi: 10.1161/ CIR.0b013e318277d6a0.

21. Lábrová R. Edoxaban – farmakologický profil. Kardiol Rev Int Med 2017; 19(1): 45–50.

22. Sahlen A, Verenhorst C, Lagerqvist B et al. Outcomes in patients treated with ticagrelor or clopidogrel after acute myocardial infarction: experiences from SWEDEHEART registry. Eur Heart J2016; 37(44): 3335– 3342. doi: 10.1093/ eurheartj/ ehw284.