Antiplatelet therapy in patients with ST-elevation myocardial infarction undergoing myocardial revascularisation: beyond clopidogrel

Abstract

Background:

Despite revascularisation, outcomes among patients presenting with ST-elevation myocardial infarction (STEMI) remain suboptimal.

Scope:

This review compares clopidogrel, ticagrelor and prasugrel as antiplatelet strategies with a particular focus on STEMI. Medline and Google Scholar were searched for relevant terms and citations from these articles were also assessed.

Findings:

While clopidogrel represented an important therapeutic advance, variations in platelet response and a relatively slow onset of action compromise outcomes in some patients. Ticagrelor and prasugrel are more effective than clopidogrel, although essentially only one large study supports each drug. Nevertheless, a detailed examination of the evidence reveals several issues that may influence the decision to prescribe ticagrelor instead of prasugrel and vice versa. Arguably, prasugrel could be the preferred strategy in STEMI, reflecting the drugs’ efficacy in clopidogrel-naïve patients, the most common group in clinical practice. Conversely, ticagrelor may be a better option than clopidogrel in clopidogrel-pretreated patients showing a mortality benefit irrespective of clopidogrel pre-treatment. The clinical benefits offered by prasugrel and ticagrelor need to be offset against the increased cost and we suggest an algorithm for using these new compounds in the primary percutaneous coronary intervention (PCI) setting. The risk of bleeding associated with prasugrel is similar to that of clopidogrel and ticagrelor following exclusion of at-risk patients. Nevertheless, prasugrel may be especially appropriate for STEMI patients undergoing PCI who are considered to be at high risk of ischaemia. Conversely, ticagrelor’s short half-life, while potentially a limitation during maintenance therapy, may reduce bleeding risk if the patient undergoes CABG during the same hospital admission, although confirmatory studies are needed.

Conclusion:

Future studies also need to address several other outstanding issues, such as the subsequent approach if patients do not undergo PCI, and to overcome limitations in and differences between the primary studies. In particular, head-to-head comparisons need to compare directly the risks and benefits of ticagrelor and prasugrel in STEMI patients. These caveats notwithstanding, ticagrelor and prasugrel markedly improve the prognosis for patients with STEMI.

Key words::

• Acute coronary syndromes
• Antiplatelet drugs
• Clopidogrel
• Myocardial revascularisation
• Prasugrel
• ST elevated myocardial infarction
• Ticagrelor

Transparency

Declaration of funding

The preparation of this manuscript was supported by a grant from Daiichi Sankyo Europe GmbH & Eli Lilly and Company.

Declaration of financial/other relationships

J.W.J. reports receiving research grants from and was speaker on (CME accredited) meetings sponsored by Astellas, Astra-Zeneca, Biotronik, Boston Scientific, Daiichi Sankyo, Lilly, Genzyme, Medtronic, Merck-Schering-Plough, Pfizer, Orbus Neich, Novartis, Roche, Servier, Sanofi Aventis, the Netherlands Heart Foundation, the Interuniversity Cardiology Institute of the Netherlands and the European Community Frame-work KP7 Programme.

J.P.C. reports receiving research grants from Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly, Guerbet Medical, Medtronic, Boston Scientific, Cordis, Stago, Fondation de France, INSERM, Fédération Française de Cardiologie, and Société Française de Cardiologie; consulting fees from Sanofi-Aventis, Eli Lilly, and Bristol-Myers Squibb; and lecture fees from Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly and AstraZeneca.

L.D.L. reports being a consultant for the Medicines Company and being on the speakers’ bureau for Daiichi-Sankyo, Lilly, AstraZeneca, Abbott Vascular, and the Medicines Company.

Acknowledgements

The authors would like to acknowledge the assistance of Mark Greener, medical writer, and Springer Healthcare Ltd in the preparation of this manuscript, supported by a grant from Daiichi Sankyo Europe GmbH and Eli Lilly and Company. The authors are responsible for the final version of the review.