Pathology of Second-Generation Everolimus-Eluting Stents Versus First-Generation Sirolimus- and Paclitaxel-Eluting Stents in Humans

• Type of Material: Article
• Authors: Fumiyuki Otsuka, CVPath Institute, Inc; Marc Vorpahl, CVPath Institute, Inc; Masataka Nakano, CVPath Institute, Inc; Jason Foerst, Virginia Tech-Carilion School of Medicine; John B. Newell, Partners Health Care Systems; Kenichi Sakakura, CVPath Institute, Inc; Robert Kutys, CVPath Institute, Inc; Elena Ladich, CVPath Institute, Inc; Aloke Finn, Emory University; Frank D. Kolodgie, CVPath Institute, Inc; Renu Virmani, CVPath Institute, Inc
• Language: English
• Date: 2014-01-14
• Publisher: American Heart Association
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 American Heart Association, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1161/CIRCULATIONAHA.113.001790
• Title of Journal or Parent Work: Circulation
• ISSN: 0009-7322
• Volume: 129
• Issue: 2
• Start Page: 211
• End Page: 223
• Grant/Funding Information: CVPath Institute Inc., Gaithersburg, Maryland, USA provided full support for this work.; Dr. Otsuka is supported by a research fellowship from the Uehara Memorial Foundation, Tokyo, Japan.
• Keywords: THROMBOSIS; Cardiovascular System & Cardiology; Peripheral Vascular Disease; BARE-METAL; ENDOTHELIALIZATION; IMPLANTATION; RANDOMIZED CONTROLLED-TRIAL; coronary restenosis; Cardiac & Cardiovascular Systems; stents; Science & Technology; thrombosis; CLINICAL-EVALUATION; FRACTURE; OUTCOMES; pathology; Life Sciences & Biomedicine; PERCUTANEOUS CORONARY INTERVENTION; FOLLOW-UP
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

BACKGROUND-: Clinical trials have demonstrated that the second-generation cobalt-chromium everolimus-eluting stent (CoCr-EES) is superior to the first-generation paclitaxel-eluting stent (PES) and is noninferior or superior to the sirolimus-eluting stent (SES) in terms of safety and efficacy. It remains unclear whether vascular responses to CoCr-EES are different from those to SES and PES because the pathology of CoCr-EES has not been described in humans. METHODS AND RESULTS-: A total of 204 lesions (SES=73; PES=85; CoCr-EES=46) from 149 autopsy cases with duration of implantation >30 days and ≤3 years were pathologically analyzed, and comparison of vascular responses was corrected for duration of implantation. The observed frequency of late and very late stent thrombosis was less in CoCr-EES (4%) versus SES (21%; P=0.029) and PES (26%; P=0.008). Neointimal thickness was comparable among the groups, whereas the percentage of uncovered struts was strikingly lower in CoCr-EES (median=2.6%) versus SES (18.0%; P<0.0005) and PES (18.7%; P<0.0005). CoCr-EES showed a lower inflammation score (with no hypersensitivity) and less fibrin deposition versus SES and PES. The observed frequency of neoatherosclerosis, however, did not differ significantly among the groups (CoCr-EES=29%; SES=35%; PES=19%). CoCr-EES had the least frequency of stent fracture (CoCr-EES=13%; SES=40%; PES=19%; P=0.007 for CoCr-EES versus SES), whereas fracture-related restenosis or thrombosis was comparable among the groups (CoCr-EES=6.5%; SES=5.5%; PES=1.2%). CONCLUSIONS-: CoCr-EES demonstrated greater strut coverage with less inflammation, less fibrin deposition, and less late and very late stent thrombosis compared with SES and PES in human autopsy analysis. Nevertheless, the observed frequencies of neoatherosclerosis and fracture-related adverse pathological events were comparable in these devices, indicating that careful long-term follow-up remains important even after CoCr-EES placement.