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Drug-Eluting Stent Thrombosis

The Kounis Hypersensitivity-Associated Acute Coronary Syndrome Revisited

Jack P. Chen, MD^_*,_*, Dongming Hou, MD, PhD^_*, Lakshmana Pendyala, MD^_*, John A. Goudevenos, MD, PhD, Nicholas G. Kounis, MD, PhD

^_* Saint Joseph's Translational Research Institute, Saint Joseph's Heart and Vascular Institute, Atlanta, Georgia
Cardiology Department, Ioannina University Medical School, Ioannina, Greece
Medical Sciences, Patras Highest Institute of Education and Technology, Patras, Greece

^_* Reprint requests and correspondence: Dr. Jack P. Chen, 5670 Peachtree Dunwoody Road, #880, Atlanta, Georgia 30342 (Email: jchen{at}sjha.org).

The advent of drug-eluting stents (DES) has revolutionized the field of interventional cardiology. Their dramatic and persistent restenotic and target lesion revascularization advantages are unquestioned. However, concerns over the rare but potentially catastrophic risk of stent thrombosis (ST) have tempered universal acceptance of these devices. Although the precise mechanism of DES ST is undoubtedly multifactorial and as yet not fully elucidated, delayed or incomplete endothelial healing clearly plays a pivotal role. Detailed histopathological data have implicated a contributory allergic or hypersensitivity component, as verified by the Food and Drug Administration's Manufacturer and User Device Experience Center and the Research on Adverse Drug/device events And Reports (RADAR) project. These findings thus suggest a potential connection with the Kounis syndrome, the concurrence of acute coronary events with allergic, hypersensitivity, anaphylactic, or anaphylactoid reactions. Potential culprits responsible for this phenomenon include: arachidonic acid metabolites such as leukotrienes and thromboxane, proteolytic enzymes such as chymase and tryptase, histamine, cytokines, and chemokines. Additionally, inflammatory cells such as macrophages, T-lymphocytes, and mast cells are probably also contributory. Autopsy-confirmed infiltrates of various inflammatory cells including lymphocytes, plasma cells, macrophages, and eosinophils have been reported in all 3 vascular wall layers and are reminiscent of those associated with the Kounis syndrome. Although the concurrence of acute coronary syndromes with hypersensitivity reactions has been long established, the specific association with DES ST remains unproven. Potential incorporation of hypersensitivity suppressive agents might represent a promising paradigm shift from efficacy to safety in future DES designs.

Key Words: allergic reaction • drug-eluting stent • hypersensitivity • Kounis • thrombosis

Abbreviations and Acronyms   ARC = Academic Research Consortium   ASA = acetylsalicylic acid   BMS = bare-metal stent(s)   DAT = dual antiplatelet therapy   DES = drug-eluting stent(s)   FDA = Food and Drug Administration   HR = hazard ratio   Ig = immunoglobulin   MACE = major adverse cardiovascular events   MI = myocardial infarction   PCI = percutaneous coronary intervention   ST = stent thrombosis   TLR = target lesion revascularization