Editors' ChoiceCardiology

Newer-Generation Drug-Eluting Stents: Heal Thyself

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Science Translational Medicine  13 Nov 2013:
Vol. 5, Issue 211, pp. 211ec190
DOI: 10.1126/scitranslmed.3007981

The first generation of drug-eluting stents was approved in the United States for treatment of coronary artery disease nearly a decade ago. These stents allow local delivery of the drugs sirolimus and paclitaxil, which inhibit the cell cycle and prevent renarrowing of the stented vessel, or restenosis. This results in reduced need for target lesion revascularization as compared with that of bare metal stents. However, with this good news comes some bad news. In rare cases, drug-eluting stents are accompanied by a higher rate of thrombosis 1 month or even a year after implantation. This devastating complication has been linked to delayed re-endothelialization of the stent, believed to be in part due to the polymer that adheres the drug to the metal surface of the stent. Newer drug-eluting stents use different biopolymers, believed to be more inert, and are made of a cobalt chromium alloy that results in great flexibility and thinner stent struts.

Otsuka et al. now provide the first large-scale pathologic description of next-generation drug-eluting stents in humans, comparing the newer cobalt-chromium everolimus-eluting stent (CoCr-EES) with first-generation drug-eluting stents. The authors evaluated a total of 204 lesions from 149 autopsy cases, in which the implants had been in place between 3 months to 3 years. Baseline characteristics were similar among the groups. Although the intimal thickness and atherosclerosis that developed in the presence of the stent did not differ among stent types, the newer CoCr-EES resulted in far fewer uncovered stent struts (2.6%) than those of the older stents (18.0 and 18.7%). The CoCr-EES stents were also associated with less inflammation and less fibrin than were the first-generation drug-eluting stents.

This report is consistent with results from randomized clinical trials that suggest that newer drug-eluting stents cause less late and very late stent thrombosis than do first-generation designs. The marked improvement in stent strut coverage with CoCr-EES implantation is consistent with the working hypothesis that stent thrombosis results in part from delayed healing. That new stent designs can improve re-endothelialization without sacrificing efficacy against pathologic restenosis suggests that these processes are indeed separable. Thus, additional improvements in both efficacy and safety are likely possible for this relatively new, but clearly beneficial, technology.

F. Otsuka et al., Pathology of second-generation everolimus-eluting stents versus first-generation sirolimus- and paclitaxel-eluting stents in humans. Circulation, published online 25 October 2013 (10.1161/​CIRCULATIONAHA.113.001790). [Abstract]

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