Coronary responses and differential mechanisms of late stent thrombosis attributed to first-generation sirolimus- and paclitaxel-eluting stents.
OBJECTIVE
The purpose of this study was to assess the mechanism(s) of late stent thrombosis (LST) and vascular healing responses in first-generation polymeric drug-eluting stents (DES).


BACKGROUND
Recent clinical trials have reported variations in late lumen loss between first-generation sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). Little is known, however, about the vascular responses, time course of healing, and underlying mechanism(s) of complications of LST between platforms in human coronary implants.


METHODS
The overall analysis included 174 cases (230 DES lesions) from the CVPath Institute's stent registry. Histomorphometry was performed on coronary stents from 127 patients (171 lesions) who died ≥ 30 days after receiving stent implants in which fibrin deposition, endothelial strut coverage, inflammatory response, and mechanism(s) of in-stent thrombosis were assessed.


RESULTS
Both platforms demonstrated increased neointimal thickness over time where values were greater in PES (mean 0.13 mm; range 0.03 to 0.20 mm) than SES (mean 0.10 mm; range 0.04 to 0.15 mm; p = 0.04). The percentage of uncovered struts was similar between SES and PES including stents with LST (SES = 21% vs. PES = 27%; p = 0.47). The underlying mechanism(s) of LST, however, was strikingly different between platforms; localized strut hypersensitivity was exclusive to SES, whereas malapposition secondary to excessive fibrin deposition was the underlying cause in PES. Moreover, although both PES and SES showed nearly complete strut coverage after 12 months for on-label use, the majority of stents placed for off-label indications remained unhealed after 12 months in both types of DES.


CONCLUSIONS
Differential mechanisms of LST involving either hypersensitivity or excessive fibrin were identified between first-generation DES in which overall stent healing was further delayed in DES placed for off-label indications.
CVPath Institute, Gaithersburg, Maryland 20878, USA.
Gaku
G
Nakazawa
Aloke V
AV
Finn
Marc
M
Vorpahl
Elena R
ER
Ladich
Frank D
FD
Kolodgie
Renu
R
Virmani
D000328:Adult; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000295:instrumentation* / Q000379:methods; D023903:Coronary Restenosis / Q000000981:diagnostic imaging / Q000209:etiology / Q000401:mortality; D023921:Coronary Stenosis / Q000000981:diagnostic imaging / Q000628:therapy*; D003328:Coronary Thrombosis / Q000000981:diagnostic imaging / Q000209:etiology / Q000401:mortality*; D054855:Drug-Eluting Stents / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000494:pharmacology*; D011475:Prosthesis Failure; D011859:Radiography; D012042:Registries; D018570:Risk Assessment; D020123:Sirolimus / Q000494:pharmacology*; D016019:Survival Analysis; D013997:Time Factors
D017239:Paclitaxel; D020123:Sirolimus