Localized Hypersensitivity and Late Coronary Thrombosis Secondary to a Sirolimus-Eluting Stent: Should We Be Cautious?

Background—The US Food and Drug Administration recently issued a warning of subacute thrombosis and hypersensitivity reactions to sirolimus-eluting stents (Cypher). The cause and incidence of these events have not been determined. Methods and Results—We present findings of a 58-year-old man who died of late stent thrombosis 18 months after receiving 2 Cypher stents for unstable angina. Although angiographic and intravascular ultrasound results at 8 months demonstrated the absence of neointimal formation, vessel enlargement was present. An autopsy showed aneurysmal dilation of the stented arterial segments with a severe localized hypersensitivity reaction consisting predominantly of T lymphocytes and eosinophils. Conclusions—The known pharmacokinetic elution profile of Cypher stents and the presence of polymer fragments surrounded by giant cells and eosinophils suggest that a reaction to the polymer may have caused late stent thrombosis. Careful long-term follow-up of patients with vessel enlargement after Cypher stent placement is recommended.

[1]  K. Maghni,et al.  Rapamycin inhibits airway leukocyte infiltration and hyperreactivity in guinea pigs , 1993, Agents and Actions.

[2]  P. Serruys,et al.  Long-Term Follow-Up of Incomplete Stent Apposition in Patients Who Received Sirolimus-Eluting Stent for De Novo Coronary Lesions: An Intravascular Ultrasound Analysis , 2003, Circulation.

[3]  Renu Virmani,et al.  Pathological Mechanisms of Fatal Late Coronary Stent Thrombosis in Humans , 2003, Circulation.

[4]  William Wijns,et al.  Sirolimus-eluting stents for treatment of patients with long atherosclerotic lesions in small coronary arteries: double-blind, randomised controlled trial (E-SIRIUS) , 2003, The Lancet.

[5]  Jeffrey W Moses,et al.  Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. , 2003, The New England journal of medicine.

[6]  N. Weissman,et al.  Regional Remodeling as the Cause of Late Stent Malapposition , 2003, Circulation.

[7]  P. Leggat,et al.  Toxicity of methyl methacrylate in dentistry. , 2003, International Dental Journal.

[8]  P. Serruys,et al.  New frontiers in cardiology: drug-eluting stents: Part II. , 2003, Circulation.

[9]  Patrick W Serruys,et al.  New frontiers in cardiology: drug-eluting stents: Part I. , 2003, Circulation.

[10]  R. Calne,et al.  Bicêtre hospital experience with sirolimus-based therapy in human renal transplantation: the Sirolimus European Renal Transplant Study. , 2003, Transplantation proceedings.

[11]  J. Yunginger,et al.  Occupational allergies caused by latex. , 2003, Immunology and allergy clinics of North America.

[12]  P. Teirstein,et al.  Pilot Trial of Oral Rapamycin for Recalcitrant Restenosis , 2003, Circulation.

[13]  P. Serruys,et al.  Two-Year Angiographic and Intravascular Ultrasound Follow-Up After Implantation of Sirolimus-Eluting Stents in Human Coronary Arteries , 2003, Circulation.

[14]  E. Trulock,et al.  Sirolimus-induced leukocytoclastic vasculitis. , 2002, Transplantation.

[15]  E. Pretorius.  Allergic reactions caused by dental restorative products. , 2002, SADJ : journal of the South African Dental Association = tydskrif van die Suid-Afrikaanse Tandheelkundige Vereniging.

[16]  P. Serruys,et al.  Intravascular Ultrasound Findings in the Multicenter, Randomized, Double-Blind RAVEL (RAndomized study with the sirolimus-eluting VElocity balloon-expandable stent in the treatment of patients with de novo native coronary artery Lesions) Trial , 2002, Circulation.

[17]  Renu Virmani,et al.  Morphological Predictors of Restenosis After Coronary Stenting in Humans , 2002, Circulation.

[18]  G. Papandreou,et al.  Twenty-eight-day efficacy and phamacokinetics of the sirolimus-eluting stent , 2002, Coronary artery disease.

[19]  Ousa,et al.  A RANDOMIZED COMPARISON OF A SIROLIMUS-ELUTING STENT WITH A STANDARD STENT FOR CORONARY REVASCULARIZATION , 2002 .

[20]  P. Tsao,et al.  Stent-Based Delivery of Sirolimus Reduces Neointimal Formation in a Porcine Coronary Model , 2001, Circulation.

[21]  Jeffrey J. Popma,et al.  Lack of Neointimal Proliferation After Implantation of Sirolimus-Coated Stents in Human Coronary Arteries: A Quantitative Coronary Angiography and Three-Dimensional Intravascular Ultrasound Study , 2001, Circulation.

[22]  Christian W Hamm,et al.  Nickel and molybdenum contact allergies in patients with coronary in-stent restenosis , 2000, The Lancet.

[23]  R. Virmani,et al.  Granulomatous 'foreign body reactions' contribute to exaggerated in-stent restenosis. , 1999, Coronary artery disease.

[24]  D B Corry,et al.  Requirement for IL-13 independently of IL-4 in experimental asthma. , 1998, Science.

[25]  M Braden,et al.  Review of the biological response to a novel bone cement containing poly(ethyl methacrylate) and n-butyl methacrylate. , 1998, Biomaterials.

[26]  E. Topol,et al.  Marked inflammatory sequelae to implantation of biodegradable and nonbiodegradable polymers in porcine coronary arteries. , 1996, Circulation.

[27]  W. J. van der Giessen,et al.  Coronary stent coatings. , 1994, Coronary artery disease.

[28]  R. Rp,et al.  Foreign body reactions. , 1988 .

[29]  J. Fox,et al.  Evaluation of ethylene-vinyl acetate copolymer as a non-inflammatory alternative to Freund's complete adjuvant in rabbits. , 1985, Laboratory animal science.

[30]  F. Happey.  Synthetic Polymers , 1955, Nature.