Pegasus study – long‑term dual antiaggregation therapy (ASA + ticagrelor) following myocardial infarction
Authors:
J. Špinar 1; L. Špinarová 2; J. Vítovec 2
Authors place of work:
Interní kardiologická klinika LF MU a FN Brno
1; I. interní kardioangiologická klinika LF MU a FN u sv. Anny v Brně
2
Published in the journal:
Kardiol Rev Int Med 2015, 17(1): 41-45
Category:
Cardiology Review
Summary
Background:
Ticagrelor is a P2Y12 receptor antagonist that has been shown to reduce the incidence of ischemic events for up to a year after an myocardial infarction acute coronary syndrome. The efficacy and safety of long‑term ticagrelor therapy beyond 1 year after a myocardial infarction is was unknown.
Methods:
We randomized 21,162 patients with a history of myocardial infarction within the previous 1– 3 years on a double‑blind basis 1 : 1 : 1 fashion to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or placebo, all treated with low‑dose aspirin, and followed them up for a median of 33 months. The primary efficacy endpoint was the composite of cardiovascular death, myocardial infarction, or stroke. The primary safety endpoint was TIMI major bleeding.
Results:
Both doses of ticagrelor significantly reduced the primary efficacy endpoint at 3 years compared to placebo, with Kaplan‑ Meier rates at 3 years of 7.85% with ticagrelor 90 mg, 7.77% with ticagrelor 60 mg, and 9.04% with placebo (HR for ticagrelor 90 mg vs. placebo was 0.85, 95% CI 0.75– 0.96, p = 0.0080; HR for ticagrelor 60 mg vs. placebo was 0.84, 95% CI 0.74– 0.95, p = 0.0043). The rates of TIMI major bleeding were higher with ticagrelor (2.60% for 90 mg, 2.30% for 60 mg and 1.06% for placebo, p < 0.001 for each dose against placebo); the rates of fatal intracranial hemorrhage or fatal bleeding were 0.63%, 0.71%, and 0.60% in the 3 arms, respectively.
Conclusions:
Treatment with ticagrelor of patients more than 1 year after a myocardial infarction with ticagrelor reduces the risk of cardiovascular death, myocardial infarction, or stroke, and slightly increases the risk of major bleeding.
Keywords:
ticagrelor – myocardial infarction – secondary prevention
Zdroje
1. Scirica BM, Vannon CH, Emanuelsson H et al. The incidence or arrhytmias and clinical arrhytmias events in patients with acute coronary syndromes treated with ticagrelor or clopidogrel in the PLATO trial. J Am Coll Cardiol 2010; 55 (10s1). doi:10.1016/ S0735– 1097(10)61007– 8.
2. Špinar J, Vítovec J. Ticagrelor a studie PLATO. Kardiol Rev Int Med 2011; 13(4): 254– 257.
3. Wallentin L, Becker RC, Budaj A et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361: 1045– 1057. doi: 10.1056/ NEJMoa0904327.
4. 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: 2354– 2394. doi: 10.1161/ CIR.0000000000000133.
5. Hamm CW, Bassand JP, Agewall S et al. ESC Guidelines 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: 2999– 3054. doi: 10.1093/ eurheartj/ ehr236.
6. 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 Guidelines. Circulation 2013; 127: e362– e425.
7. Steg PG, James SK, Atar D et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST‑segment elevation. Eur Heart J 2012; 33: 2569– 2619. doi: 10.1093/ eurheartj/ ehs215.
8. Bonaca MP, Bhatt DL, Cohen M for the PEGASUS investigators: Ticagrelor for long‑term secondary prevention of atherothrombotic events in patients with prior myocardial Infarctio. N Engl J Med 2015. Epub ahead of print. doi: 10.1056/ NEJMoa1500857.
9. 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: 437– 444. doi: 10.1016/ j.ahj.2013.12.020.
10. 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: 2736– 2747. doi: 10.1161/ CIRCULATIONAHA.110.009449.
11. Bhatt DL, Fox KA, Hacke W et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 2006; 354: 1706– 1717.
12. Bhatt DL, Flather MD, Hacke W et al. Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial. J Am Coll Cardiol 2007; 49: 1982– 1988.
13. Mauri L, Kereiakes DJ, Yeh RW et al. Twelve or 30 months of dual antiplatelet therapy after drug‑eluting stents. N Engl J Med 2014; 371(23): 2155– 2166. doi: 10.1056/ NEJMoa1409312.
14. 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: e354– e471. doi: 10.1161/ CIR.0b013e318277d6a0.
15. Montalescot G, Sechtem U, Achenbach S et al. 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: 2949– 3003. doi: 10.1093/ eurheartj/ eht296.
Štítky
Paediatric cardiology Internal medicine Cardiac surgery CardiologyČlánok vyšiel v časopise
Cardiology Review
2015 Číslo 1
Najčítanejšie v tomto čísle
- TDM of digoxin in clinical practice
- Drug interaction and current clinical practice
- Cardiac resynchronization therapy – when should it be indicated and for whom?
- TDM of antibiotics in clinical practice