Absence of metal allergy in patients with very late drug-eluting stent thrombosis: A pilot study

Abstract

Stent thrombosis (ST) is a rare but devastating complication of percutaneous coronary intervention (PCI) associated with myocardial infarction and death. While ST <1 year after PCI occurs more frequently and with similar frequency after bare metal stent and drug-eluting stent (DES) implantation, very late ST >1 year after PCI appears to be more germane to DES, or at least to first-generation DES, i.e., the Cypher® sirolimus-eluting stent (SES; Cordis, Johnson & Johnson, Miami Lakes, FL) and the Taxus® paclitaxel-eluting stent (PES; Boston Scientific, Natick, MN) [ [1] Windecker S. Meier B. Late coronary stent thrombosis. Circulation. 2007; 116: 952-965 Crossref Scopus (208) Google Scholar ]. The mechanisms underlying very late ST with DES are poorly understood, but delayed vessel healing, chronic inflammation, incomplete endothelialization, stent malapposition, and resistance to antiplatelet agents appear to contribute to the pathogenesis [ [1] Windecker S. Meier B. Late coronary stent thrombosis. Circulation. 2007; 116: 952-965 Crossref Scopus (208) Google Scholar ]. Specifically, autopsy studies and intracoronary thrombus aspirates from patients with very late ST of DES have indicated the presence of hypersensitivity reactions in the stented coronary segment with infiltrating eosinophils and T lymphocytes, suggesting that delayed hypersensitivity to DES, i.e., the metallic stent platform, the drug-eluting polymer, and/or the antiproliferative drugs (sirolimus and paclitaxel), may be a prevailing mechanism [ 2 Virmani R. Guagliumi G. Farb A. et al. Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: should we be cautious?. Circulation. 2004; 109: 701-705 Crossref PubMed Scopus (1400) Google Scholar , 3 Virmani R. Farb A. Guagliumi G. Kolodgie F.D. Drug-eluting stents: caution and concerns for long-term outcome. Coron Art Dis. 2004; 15: 313-318 Crossref PubMed Scopus (220) Google Scholar , 4 Nebecker J.R. Virmani R. Bennett C.L. et al. Hypersensitivity cases associated with drug-eluting coronary stents: a review of available cases from the Research on Adverse Drug Events and Reports (RADAR) project. J Am Coll Cardiol. 2006; 47: 175-181 Abstract Full Text Full Text PDF PubMed Scopus (589) Google Scholar , 5 Cook S. Ladich E. Nakazawa G. et al. Correlation of intravascular ultrasound findings with histopathogical analysis of thrombus aspirates in patients with very late drug-eluting stent thrombosis. Circulation. 2009; 120: 391-399 Crossref PubMed Scopus (412) Google Scholar ]. The metallic stent platform of most stents including first-generation DES is made from 316 L stainless steel, which contains and releases sensitizing metals, e.g., nickel, chromium, and molybdenum, and limited evidence has indicated that contact allergy to metals as determined by epicutaneous patch tests is more prevalent in patients with in-stent restenosis of bare metal stents [ 6 Köster R. Vieluf D. Kiehn M. et al. Nickel and molybdenum contact allergies in patients with coronary in-stent restenosis. Lancet. 2000; 356: 1895-1897 Abstract Full Text Full Text PDF PubMed Scopus (452) Google Scholar , 7 Iijima R. Ikari Y. Amiya E. et al. The impact of metallic allergy on stent implantation: metal allergy and recurrence of in-stent restenosis. Int J Cardiol. 2005; 104: 319-325 Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar ]. It was recently also suggested that ST after DES can represent a manifestation of acute coronary syndrome caused by allergic conditions, i.e., the Kounis syndrome [ [8] Chen J.P. Hou D. Pendyala L. Goudevenos J.A. Kounis N.G. Drug-eluting stent thrombosis: the Kounis hypersensitivity-associated acute coronary syndrome revisited. JACC Cardiovasc Interv. 2009; 2: 583-593 Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar ]. This specific association remains unproven and the impact of metal allergy on ST has not, to our knowledge, been reported previously. We therefore performed a small pilot study in order to assess the prevalence of metal allergy as determined by positive patch tests in patients with very late ST after DES.