Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk.
OBJECTIVE
This study examined human drug-eluting stents (DES) to determine the long-term effects of these stents on coronary arterial healing and identified mechanisms underlying late stent thrombosis (LST).


BACKGROUND
Although DES reduce the need for repeat revascularization compared with bare-metal stents (BMS), data suggest the window of thrombotic risk for Cypher (Cordis Corp., Miami Lakes, Florida) and Taxus (Boston Scientific Corp., Natick, Massachusetts) DES extends far beyond that for BMS.


METHODS
From a registry of 40 autopsies of DES (68 stents), 23 DES cases of >30 days duration were compared with 25 matched autopsies of BMS implantation. Late stent thrombosis was defined as an acute thrombus within a stent >30 days old.


RESULTS
Of 23 patients with DES >30 days old, 14 had evidence of LST. Cypher and Taxus DES showed greater delayed healing characterized by persistent fibrin deposition (fibrin score 2.3 +/- 1.1 vs. 0.9 +/- 0.8, p = 0.0001) and poorer endothelialization (55.8 +/- 26.5%) compared with BMS (89.8 +/- 20.9, p = 0.0001). Moreover, DES with LST showed more delayed healing compared with patent DES. In 5 of 14 patients suffering LST, antiplatelet therapy had been withdrawn. Additional procedural and pathologic risk factors for LST were: 1) local hypersensitivity reaction; 2) ostial and/or bifurcation stenting; 3) malapposition/incomplete apposition; 4) restenosis; and 5) strut penetration into a necrotic core.


CONCLUSIONS
The Cypher and Taxus DES result in delayed arterial healing when compared with BMS of similar implant duration. The cause of DES LST is multifactorial with delayed healing in combination with other clinical and procedural risk factors playing a role.
Joner
Michael
M
CVPath, International Registry of Pathology, Gaithersburg, Maryland 20878, USA.
Finn
Aloke V
AV
Farb
Andrew
A
Mont
Erik K
EK
Kolodgie
Frank D
FD
Ladich
Elena
E
Kutys
Robert
R
Skorija
Kristi
K
Gold
Herman K
HK
Virmani
Renu
R
D000328:Adult; D000368:Aged; D023903:Coronary Restenosis; D003328:Coronary Thrombosis / Q000209:etiology* / Q000401:mortality; D003331:Coronary Vessels / Q000473:pathology*; D016757:Death, Sudden, Cardiac; D005260:Female; D006801:Humans; D008297:Male; D008670:Metals; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000401:mortality; D017239:Paclitaxel; D020123:Sirolimus; D015607:Stents / Q000009:adverse effects*; D014945:Wound Healing
D008670:Metals; D017239:Paclitaxel; D020123:Sirolimus