Tackling the thrombotic burden in patients with acute coronary syndrome and diabetes mellitus

Abstract

Patients with diabetes mellitus (DM) and coronary artery disease, particularly those presenting with acute coronary syndromes (ACS), have a higher risk of developing ischemic complications than their nondiabetic counterparts. Although ACS patients with DM benefit more than normoglycemic ACS patients from early coronary angiography and revascularization, they remain at a higher risk of complications following percutaneous coronary intervention and bypass surgery. The DM-associated prothrombotic state has been implicated in the pathogenesis of these complications and growing data supports the notion that potent platelet inhibition is of paramount importance in order to optimize outcomes of DM patients presenting with ACS. This article focuses on the evidence supporting the concept that augmented platelet reactivity and impaired responsiveness to oral antiplatelet agents are influential drivers of the increased propensity of DM patients with ACS to develop thrombotic complications. In particular, strategies to enhance platelet P2Y₁₂ receptor inhibition, a key factor to improve outcomes in this patient population, are reviewed.

Keywords::

• acute coronary syndromes
• antiplatelet drugs
• aspirin
• clopidogrel
• diabetes
• P2Y₁₂ inhibitors
• percutaneous coronary intervention
• platelets
• prasugrel
• ticagrelor

Financial & competing interests disclosure

Dominick Angiolillo reports receiving honoraria for lectures from Bristol-Myers Squibb, sanofi-aventis, Eli Lilly and Co., and Daiichi Sankyo, Inc.; consulting fees from Bristol-Myers Squibb, sanofi-aventis, Eli Lilly and Co., Daiichi Sankyo, Inc., The Medicines Company, Portola, Novartis, Medicure, Accumetrics, Arena Pharmaceuticals and Astra Zeneca; and research grants from Bristol-Myers Squibb, sanofi-aventis, GlaxoSmithKline, Otsuka, Eli Lilly and Co., Daiichi Sankyo, Inc., The Medicines Company, Portola, Accumetrics, Schering-Plough, Astra Zeneca, Eisai, and Johnson and Johnson. Marco Roffi reports receiving honoraria for lectures and consulting fees from Eli Lilly and Co., and Daiichi Sankyo, Inc. Antonio Fernandez-Ortiz reports receiving honoraria for lectures and consulting fees from Eli Lilly and Co., Daiichi Sankyo Inc., Astra Zeneca, Bristol-Myers Squibb, and GlaxoSmithKline. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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

Notes

ACS: Acute coronary syndrome; DES: Drug-eluting stent; DM: Diabetes mellitus; EVASTENT: Évaluation Coût/Efficacité du Stent Actif au Sirolimus Chez les Patients Diabétiques et Non Diabétiques; HR: Hazard ratio; IDDM: Insulin-dependent DM; OR: Odds ratio; PCI: Percutaneous coronary intervention.

ACS: Acute coronary syndrome; ACUITY: Acute Catheterization and Urgent Intervention Triage Strategy; DM: Diabetes mellitus; GPI: Glycoprotein IIb/IIIa inhibitor; MI: Myocardial infarction; PCI: Percutaneous coronary intervention.