Atherosclerosis in the neointima may represent a new risk factor for late stent thrombosis, an autopsy study showed.
In more than 400 stented lesions, neoatherosclerosis was more commonly found with drug-eluting stents than with bare-metal stents (31% versus 16%, P<0.001), according to Renu Virmani, MD, of CVPath Institute, in Gaithersburg, Md., and colleagues.
The duration of the implant was significantly shorter for drug-eluting stents in all cases of neoatherosclerosis (median 420 versus 2,160 days) and in cases involving unstable lesions characterized as thin-cap fibroatheromas or plaque rupture (mean 1.5 versus 6.1 years), the researchers reported in the March 15 issue of the Journal of the American College of Cardiology.
Action Points
- Explain that atherosclerosis in the neointima may represent a new risk factor for late stent thrombosis, according to an autopsy study.
- Note that neoatherosclerosis was more commonly found and occurred earlier after implanation with drug-eluting stents than with bare-metal stents.
- Note that limitations of the study included the nonrandom design and possibility that the study population was biased toward patients dying of drug-eluting stent complications, which could result in inflated rates of stent thrombosis.
"These observations raise the question whether neoatherosclerosis seen within drug-eluting stents as well as bare-metal stents at follow-up may in part be responsible for some late thrombotic events," they wrote.
"The occurrence of uncovered struts complicated by a dysfunctional endothelium remains the primary cause of late stent thrombosis in drug-eluting stents," they continued. "Nevertheless, the present study adds another risk factor, namely, in-stent plaque rupture, although a rare event."
Virmani and her colleagues looked at data from the CVPath stent registry of 299 autopsies of individuals who had been implanted with a stent for more than 30 days before they died.
There were 406 lesions -- 197 with bare-metal stents and 209 with drug-eluting stents. The drug-eluting stents were almost evenly divided between the sirolimus-eluting stent (Cypher) and the paclitaxel-eluting stent (Taxus).
Stent-related deaths from thrombosis were more common with drug-eluting stents (20% versus 4%), whereas in-stent restenosis as a cause of death was more frequent with bare-metal stents (28% versus 7%). Both differences were significant at P<0.001.
Neoathersclerosis -- defined as foamy macrophage clusters with or without calcification, fibroatheromas, thin-cap fibroatheromas, and ruptures with thrombosis -- occurred in a greater proportion of drug-eluting stents, and after a shorter duration of implantation, compared with bare-metal stents.
For stents that were implanted for less than two years, neoatherosclerosis was more common for sirolimus-eluting stents than for paclitaxel-eluting stents (37% versus 21%, P=0.021). There was no difference in the rate for longer-duration implants.
Advanced lesions -- thin-cap fibroatheromas or plaque ruptures -- tended to be more frequent with bare-metal stents (4% versus 1%), the difference was not statistically significant (P=0.17) and likely resulted from the longer duration of bare-metal stents.
Independent risk factors for neoatherosclerosis included younger age, longer implant durations, use of either sirolimus-eluting or paclitaxel-eluting stents, and underlying unstable plaques (P≤0.004 for all).
"The pathological findings regarding vascular responses to bare-metal stents and drug-eluting stents clearly point to the importance of complete and effective covering of the stented neointima by endothelium, namely, endothelialization, or the lack thereof, in leading to good or adverse outcomes, including late thrombosis," according to L. Maximilian Buja, MD, of the University of Texas ľֱ School at Houston.
But, he wrote in an accompanying editorial, "there also is an important place for experimental studies to evaluate pathophysiological phenomena, including extent of endothelial formation and maturation and control of fibrocellular intimal thickening, as new approaches to drug-eluting stents are being developed."
Virmani and her colleagues acknowledged some limitations of the study, including the nonrandom design and possibility that the study population was biased toward patients dying of drug-eluting stent complications, which could result in inflated rates of stent thrombosis.
Disclosures
CVPath Institute provided full support for the study.
Virmani reported receiving research support from Medtronic AVE, Abbott Vascular, Atrium Medical, OrbusNeich Medical, Terumo Corporation, Cordis Corporation, BioSensors International, Biotronik, and Alchimedics, and serving as a consultant for Medtronic AVE, Abbott Vascular, W.L. Gore, Atrium Medical, and Lutonix. One of her co-authors is supported by an NIH grant, the Carlyle Fraser Heart Center at Emory University, and a sponsored research agreement with Medtronic and St. Jude Medical, and is a consultant for Abbott Vascular and Cordis.
Buja did not report any conflicts of interest.
Primary Source
Journal of the American College of Cardiology
Nakazawa G, et al "The pathology of neoatherosclerosis in human coronary implants: bare-metal and drug-eluting stents" J Am Coll Cardiol 2011; DOI: 10.1016/j.jacc.2011.01.011.
Secondary Source
Journal of the American College of Cardiology
Buja L "Vascular responses to percutaneous coronary intervention with bare-metal stents and drug-eluting stents: A perspective based on insights from pathological and clinical studies" J Am Coll Cardiol 2011; DOI: 10.1016/j.jacc.2010.11.033.