Ticagrelor: A Review in Long Term Secondary Prevention of Cardiovascular Events
- 564 Downloads
Ticagrelor (Brilique®) is an orally administered P2Y12 inhibitor. A long-term (maintenance) regimen of ticagrelor 60 mg twice daily is indicated in the EU for coadministration with low-dose aspirin 75–150 mg/day for the secondary prevention of atherothrombotic events in high-risk patients with a history of myocardial infarction (MI) of at least 1 year. Approval is based on the results of the PEGASUS-TIMI 54 trial that compared ticagrelor with placebo (in conjunction with low-dose aspirin) in stable patients who had had a spontaneous MI 1–3 years prior to enrolment and were at high risk of atherothrombotic events. At 3 years, the composite primary efficacy endpoint of cardiovascular (CV) death, MI or stroke occurred in significantly fewer ticagrelor 60 mg twice daily than placebo recipients. Long-term ticagrelor had a manageable tolerability and safety profile. The risk of TIMI major bleeding (primary safety endpoint) was significantly increased in ticagrelor 60 mg twice daily versus placebo recipients; however, the risk appeared to decline after the first year of therapy. Landmark analyses have demonstrated that patients with a history of MI remain at a persistent high risk of the composite primary endpoint up to 5 years after the event. Furthermore, these analyses demonstrated that the efficacy of ticagrelor 60 mg twice daily was maintained over time, with less excess in bleeding after the first year. Thus, long-term dual antiplatelet therapy with ticagrelor 60 mg twice daily and low-dose aspirin is a valuable new option for the secondary prevention of atherothrombotic events in stable, high-risk patients with a history of MI of at least 1 year.
During the peer review process, the manufacturer of ticagrelor was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.
Compliance with Ethical Standards
The preparation of this review was not supported by any external funding.
Conflict of interest
Zaina T. Al-Salama, Gillian M. Keating and Susan J. Keam are salaried employees of Adis/Springer, are responsible for the article content and declare no relevant conflicts of interest.
Additional information about this Adis Drug Review can be found at http://www.medengine.com/Redeem/BB4CF06072661B7C.
- 4.European Medicines Agency. Brilique (ticagrelor) 60 mg film-coated tablets: EU summary of product characteristics. 2015. http://www.ema.europa.eu/. Accessed 7 Nov 2017.
- 8.Storey RF, Angiolillo DJ, Patil SB, 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.CrossRefPubMedGoogle Scholar
- 14.European Medicines Agency. Brilique (ticagrelor): EU assessment report. 2011. http://www.ema.europa.eu/. Accessed 7 Nov 2017.
- 22.Teng R, Muldowney S, Zhao Y, et al. Pharmacokinetics and pharmacodynamics of ticagrelor in subjects in hemodialysis and subjects with normal renal function [abstract plus poster P288]. In: 2017 ACCP annual meeting. 2017.Google Scholar
- 26.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.CrossRefPubMedGoogle Scholar
- 31.Dellborg M, Bonaca MP, Storey R, et al. Efficacy and safety with ticagrelor in patients with prior myocardial infarction in the approved European label: insights from PEGASUS-TIMI 54 [abstract no. P3670 plus poster]. Eur Heart J. 2017;38(Suppl 1):794–5.Google Scholar
- 34.Euopean Medicines Agency. Plavix (clopidogrel) 75 mg film-coated tablets: EU summary of product characteristics. 2010. http://www.ema.europa.eu/. Accessed 7 Nov 2017.
- 35.European Medicines Agency. Effient (prasugrel) 5 mg film-coated tablets: EU summary of product characteristics. 2016. http://www.ema.europa.eu/. Accessed 7 Nov 2017.
- 40.Valgimigli M, Bueno H, Byrne RA, et al. ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: the Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2017. https://doi.org/10.1093/eurheartj/ehx419.PubMedCentralCrossRefPubMedGoogle Scholar
- 41.Ibanez B, James S, Agewall S, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2017. https://doi.org/10.1093/eurheartj/ehx393.PubMedCrossRefGoogle Scholar
- 42.Roffi M, Patrono C, Collet JP, et al. 2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016;37(3):267–315.CrossRefPubMedGoogle Scholar
- 43.Cosentino N, Campodonico J, Milazzo V, et al. 1-year risk stratification of patients with acute myocardial infarction according to the pegasus-timi 54 criteria [abstract no. P3639]. Eur Heart J. 2017;38(Suppl 1):784.Google Scholar