Correspondence
Bare-Metal versus Drug-Eluting Coronary Stents
N Engl J Med 2008; 358:2516-2518June 5, 2008
- Article
To the Editor:
Marroquin et al. (Jan. 24 issue)1 attempt to address the lack of evidence regarding off-label use of drug-eluting stents. However, their use of a historical comparison group that predated the group with drug-eluting stents by up to 9 years raises major concerns. First, the control group that received bare-metal stents included all patients who received a stent between 1997 and 2002. Patients treated with bare-metal stents in 2004 and 2006 were considered to be highly selected and were excluded from the study. However, the group with drug-eluting stents that made up the remaining 78% of patients who received a stent during the same period was also, therefore, a selected group. Inevitably, this selection resulted in bias, as illustrated by the markedly different percentages of patients with important confounders. Second, randomized trials have largely compared drug-eluting stents with their thick-strut, stainless-steel bare-metal-stent platforms, limiting generalizability. The development of thin-strut, cobalt–chromium bare-metal stents has reduced the rate of restenosis.2 Thus, the use of a historical control group in the study by Marroquin et al. makes the results equally difficult to extrapolate to contemporary clinical practice.
David Austin, M.R.C.P.
Jill P. Pell, M.D.
University of Glasgow, Glasgow G12 8RZ, United KingdomKeith G. Oldroyd, M.D.
Western Infirmary, Glasgow G11 6NT, United Kingdom
keith.oldroyd@northglasgow. scot. nhs. uk Drs. Austin and Pell report receiving research funding from Boston Scientific; and Dr. Oldroyd, speaking and consulting fees from Boston Scientific, Medtronic, and Cordis.
No other potential conflict of interest relevant to this letter was reported.
2 References1
Marroquin OC ,Selzer F ,Mulukutla SR , et al. A comparison of bare-metal and drug-eluting stents for off-label indications. N Engl J Med 2008;358:342-352
Full Text | Web of Science | Medline2
Tung R ,Kaul S ,Diamond GA ,Shah PK . Drug-eluting stents for the management of restenosis: a critical appraisal of the evidence. Ann Intern Med 2006;144:913-919
Web of Science | Medline
To the Editor:
Despite the careful nature of the article by Marroquin and colleagues, we believe there are some drawbacks. First, the patients were followed for 1 year, whereas adverse events related to drug-eluting-stent thrombosis occur mainly after 1 year.1 Very late stent thrombosis, which is the real Achilles' heel of drug-eluting stents as compared with bare-metal stents, occurs by definition more than 1 year after stent implantation.2 These adverse outcomes seem specifically evident for some off-label indications: the only randomized trial of drug-eluting stents as compared with bare-metal stents in saphenous-vein grafts showed higher long-term mortality after the implantation of drug-eluting stents, partly because of a higher rate of thrombosis-related events associated with drug-eluting stents.3
Second, the authors generated multivariable models with the medications at discharge as covariables, but they did not consider medications given at follow-up: dual antiplatelet therapy was given for 1 year to 71.7% of patients treated with drug-eluting stents as compared with 5.9% of patients treated with bare-metal stents. This finding may affect the outcomes analyzed, since dual antiplatelet therapy for 1 year is known to reduce the rates of death and myocardial infarction, particularly among patients in unstable condition4; these patients constituted approximately two thirds of the patients assessed.
4 ReferencesPierfrancesco Agostoni, M.D.
Paul Vermeersch, M.D.
Antwerp Cardiovascular Institute Middelheim, 2020 Antwerp, Belgium
agostonipf@gmail.com 1
Stone GW ,Moses JW ,Ellis SG , et al. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents. N Engl J Med 2007;356:998-1008
Full Text | Web of Science | Medline2
Cutlip DE ,Windecker S ,Mehran R , et al. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation 2007;115:2344-2351
CrossRef | Web of Science | Medline3
Vermeersch P ,Agostoni P ,Verheye S , et al. Increased late mortality after sirolimus-eluting stents versus bare-metal stents in diseased saphenous vein grafts: results from the randomized DELAYED RRISC Trial. J Am Coll Cardiol 2007;50:261-267
CrossRef | Web of Science | Medline4
The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators
Full Text | Web of Science | Medline
Author/Editor Response
In response to Austin et al., our decision to exclude the patients treated with bare-metal stents in 2004 and 2006 was made because soon after the Food and Drug Administration's approval of drug-eluting stents in 2003, there was a major selection bias toward inserting bare-metal stents in patients with acute conditions and high-risk characteristics (e.g., cardiogenic shock), as seen in our registry and that of others.1 Inclusion of these patients would have resulted in a markedly higher-than-expected at-risk population of patients treated with bare-metal stents as compared with patients treated with drug-eluting stents. Furthermore, although we agree that this exclusion resulted in a “selected group” of patients receiving drug-eluting stents during that time, it was a group with significantly more coexisting conditions than those receiving bare-metal stents in the earlier waves. These conditions included diabetes, renal disease, previous percutaneous coronary intervention, multivessel coronary artery disease, and American College of Cardiology/American Heart Association types B2 and C lesions — all characteristics that would tend to minimize rather than accentuate any potential benefit of drug-eluting stents as compared with bare-metal stents.
Agostoni and Vermeersch observe, on the basis of their own data, that patients with saphenous-vein grafts who are treated with drug-eluting stents have higher long-term mortality than patients treated with bare-metal stents.2 However, their small randomized trial (involving 75 patients) was not powered to detect differences in mortality; more important, this difference appears to be driven primarily by the exceptionally low 3-year mortality rate among patients treated with bare-metal stents (0%), rather than by an extraordinarily high mortality rate among the patients treated with drug-eluting stents. As a comparison, among the 480 patients in our study who had saphenous-vein grafts, the 1-year mortality rates were 7.3% for those treated with bare-metal stents and 5.3% for those treated with drug-eluting stents. With regard to the authors' point about medications at follow-up, although adjustment for medications at the 1-year follow-up could have affected risk estimates for end points such as myocardial infarction, this approach cannot be used to adjust for the rate of death, because it is not known whether the patients who died had been taking the medications in the 1-year interim.
Finally, although we agree with Agostoni and Vermeersch that very late stent thrombosis is the Achilles' heel of drug-eluting stents as compared with bare-metal stents, before our study, there was little information about the short- and long-term comparative safety and efficacy of these devices for off-label indications. Our study has filled the short-term knowledge gap with data from 1 year of follow-up, and with the recent receipt of funding from the National Heart, Lung, and Blood Institute Dynamic Registry for continued follow-up of these patients, it is our goal to help fill the knowledge gap regarding the long-term safety and efficacy of these devices.
2 ReferencesOscar C. Marroquin, M.D.
Suresh R. Mulukutla, M.D.
University of Pittsburgh, Pittsburgh, PA 15213
marroquinoc@upmc.edu Kevin E. Kip, Ph.D.
University of South Florida, Tampa, FL 336121
Beohar N ,Davidson CJ ,Kip KE , et al. Outcomes and complications associated with off-label and untested use of drug-eluting stents. JAMA 2007;297:1992-2000
CrossRef | Web of Science | Medline2
Vermeersch P ,Agostoni P ,Verheye S , et al. Increased late mortality after sirolimus-eluting stents versus bare-metal stents in diseased saphenous vein grafts: results from the randomized DELAYED RRISC Trial. J Am Coll Cardiol 2007;50:261-267
CrossRef | Web of Science | Medline
- Citing Articles (2)
Citing Articles
1
Xiaojun Liu, Yunhui Cheng, Jian Yang, Ling Xu, Chunxiang Zhang. (2012) Cell-specific effects of miR-221/222 in vessels: Molecular mechanism and therapeutic application. Journal of Molecular and Cellular Cardiology 52:1, 245-255
CrossRef2
Judit E. Puskas, Lyn G. Muñoz-Robledo, Robert A. Hoerr, John Foley, Steven P. Schmidt, Michelle Evancho-Chapman, Jinping Dong, Chris Frethem, Greg Haugstad. (2009) Drug-eluting stent coatings. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology 1:4, 451-462
CrossRef
