PEGASUS – Ticagrelor in secondary prevention on patients after a myocardial infarction
Authors:
Jindřich Špinar 1,3; Lenka Špinarová 2; Jiří Vítovec 2
Authors‘ workplace:
Interní kardiologická klinika LF MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Jindřich Špinar, CSc., FESC
1; I. interní kardio-angiologická klinika LF MU a FN u sv. Anny Brno, přednostka prof. MUDr. Lenka Špinarová, CSc., FESC
2; Mezinárodní centrum klinického výzkumu – FN u sv. Anny Brno
3
Published in:
Vnitř Lék 2015; 61(6): 511-515
Category:
Original Contributions
Overview
Background:
Ticagrelor is a P2Y12 receptor antagonist that has been shown to reduce ischemic events for up to a year after an acute coronary syndrome. The efficacy and safety of long-term ticagrelor therapy beyond 1 year after a myocardial infarction is unknown.
Methods:
We randomized 21,162 patients with a history of myocardial infarction within the prior 1–3 years in a double-blind 1 : 1 : 1 fashion to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or placebo, all with low-dose aspirin, and followed them 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 combined efficacy endpoint 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 0.85, 95% CI 0.75–0.96, p = 0.0080; HR for ticagrelor 60 mg vs placebo 0.84, 95% CI 0.74–0.95, p = 0.0043). 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 intracranial hemorrhage or fatal bleeding were 0.63 %, 0.71 % and 0.60 % in the 3 arms, respectively.
Conclusions:
Treatment of patients more than 1 year after a myocardial infarction with ticagrelor reduces the risk of cardiovascular death, myocardial infarction, or stroke, and increases the risk of major bleeding.
Key words:
myocardial infarction – secondary prevention – ticagrelor
Sources
1. Scirica BM, Cannon CP, Emanuelsson H et al. The incidence or arrhythmias and clinical arrhythmias events in patients with acute coronary syndromes treated with ticagrelor or clopidogrel in the PLATO trial. JACC 2010; 55(10s1): A108.E1006-A108.E1006. Dostupné z DOI: <http://dx.doi.org/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(11): 1045–1057.
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(25): 2354–2394.
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(23): 2999–3054.
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(4): e362-e425. Dostupné z DOI: <http://dx.doi.org/10.1161/CIR.0b013e3182742cf6>.
7. 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.
8. Bonaca MP, Bhatt DL, Cohen M et al. PEGASUS investigators. Long--term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 2015; 372(19):1791–1800. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa150087>.
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(4): 437–444.e5. Dostupné z DOI: <http://dx.doi.org/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(23) 2736–2747.
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(16): 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(19): 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.
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(25): e354-e471. Dostupné z DOI: <http://dx.doi.org/10.1161/CIR.0b013e318277d6a0>.
15. Task Force Members, Montalescot G, Sechtem U 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(38): 2949–3003.
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