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Commentary
On Registries and Labels
February 2010
The outcomes that can be expected after Cypher stent implantation have been well publicized and the results from other smaller and larger registries of drug-eluting stent (DES) implantations have been reported and have highlighted the differences in outcomes in “off-label” versus “on-label” usage. For example, the pooled-analysis of RAVEL, SIRIUS, E-SIRIUS and C-SIRIUS1 and the NEW SIRIUS analysis2 (pooled E-SIRIUS and C-SIRIUS) have reported on the 4- and 5-year outcomes of Cypher stents compared to the bare-metal equivalent. With regard to “off-label” versus “on-label” outcomes, in 2007 Beohar et al3 and Win et al4 reported worse outcomes in “off-label” use of DES. Moreover, the MATRIX Registry5 involving over 1,500 patients with “real-world” DES implantation reported a total and cardiac mortality of 3.3% and 1%, respectively through 2 years of follow-up of patients receiving the Cypher stent; MI occurred in 4%, TVR in 10.7% and definite and probable stent thrombosis occurred in 0.7% and 1.1%, respectively. The rates of MI and TVR were higher in “off-label” compared to “on-label” patients being 4.4% versus 0.9% and 11.6% versus 4.5%, respectively. Stent thrombosis and death were not statistically different (1.1% vs. 0.5% and 3.4% vs. 2.7%). A similar pooled-analysis of TAXUS I, II, II-SR, IV and V6 and two large registries — ARRIVE 17 and OLYMPIA8 — have produced similar conclusions using the Taxus stent technology. It is thus well recognized that the results of DES implantation in “off-label” cases will not be as good as in those with “on-label” indications but nevertheless the outcomes will be better than bare-metal stent use in the more complex subsets of patients requiring “off-label” use.
Unfortunately, the conclusions drawn from Bezerra in this issue of the Journal9 are of limited value to interventionists, not only because of some shortcomings of the study itself, but because DES technology, implantation techniques and after-care medical therapy have all advanced since this registry was originally conducted. Recently, for example, two large trials have reported their outcome data in “real-world”/“off-label” cases and in one of these, a comparison was made with the Cypher stent. The 2-year follow-up in the LEADERS trial10 showed similar MACE rates with the novel Biomatrix® stent (biolimus-eluting from the abluminal surface, with biodegradable polymer) compared to the sirolimus-eluting Cypher stent (with durable polymer), but a lower incidence of stent thrombosis in those patients ceasing dual antiplatelet therapy. The SPIRIT IV trial11 also reported significantly lower rates of late complications using the cobalt-chromium Xience V® (everolimus-eluting) stent compared to the Taxus® Express™ (paclitaxel-eluting) stent. Stent thrombosis at 1 year was only 0.16% in the Xience V group compared to 0.82% in the Taxus group. If results continue to improve with advancing stent technology and more targeted drug delivery, hopefully the problems of in-stent restenosis and stent thrombosis will be confined to history. We think that it is important to recognize that carefully collected and complete follow-up data from large registry studies of implanted third- and fourth-generation stents will continue to provide important information in this regard in support of evidence provided by randomized clinical trials.
References
1. Schofer J. Cypher sirolimus-eluting coronary stent. Confidence in long-term outcomes. 4 year follow-up. Presented at European Society of Cardiology, Barcelona, Spain. September 2006. https://www.cordis.com/active/crdus/en_US/html/cordis/ downloads/ press/155_5002_1_ESIRIUS_4Yr_PR.pdf 2. Schampaert E, Schofer J, Breithardt G, et al. A European and Canadian multicenter randomized, double-blind trial of the sirolimus-eluting stent (SES) in patients with de novo native coronary artery lesions (New-SIRIUS): 5-year clinical outcomes. Circulation 2007;116(SupplII):466. 3. 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. 4. Win HK, Caldera AE, Maresh K, et al; EVENT Registry Investigators. Clinical outcomes and stent thrombosis following off-label use of drug-eluting stents. JAMA 2007;297:2001–2009. 5. The MATRIX Registry. Presented at the American College of Cardiology 56th Annual Scientific Session, March 26th, 2007 – Dangas GD. Two-year patient registry results support safety and efficacy of Cypher sirolimus-eluting coronary stent in “real-world” uses. https://www.cordis.com 6. Taxus Stent (SR) 4-year meta-analysis reinforces the positive safety/efficacy profile. Taxus I, II-SR, IV, V. https://www.taxus-stent.com/usa/Cont_Data_Safety_DES.html 7. ARRIVE Registry analysis demonstrates continued safety and efficacy of TAXUS Stent in complex real-world patients. https://www.bostonscientific.mediaroom. com/index. php?s=43&item=684 8. Thomas M, Ahmed W, Mendiz O, Mascioli S; on behalf of The TAXUS OLYMPIA Investigators. Real-world results with TAXUS Liberte: One-year results from the TAXUS OLYMPIA global post-approval registry with emphasis on diabetic patients. Eur Heart J 2007;28(Abstract)Suppl:135. 9. Bezerra H, Perin E, Berger P, et al. One-year outcomes of unselected recipients of sirolimus-eluting stents: The Cypher stent U.S. post-marketing surveillance registry. J Invasive Cardiol 2010;22:48–55. 10. LEADERS: Two-year follow-up from a prospective randomized trial of biolimus A9-eluting stents with a bioabsorbable polymer vs. sirolimus-eluting stents with a durable polymer. Klauss Volker. Presented at TCT 2009, San Francisco, USA. September 21–25, 2009. 11. SPIRIT IV: A prospective randomized trial comparing an everolimus-eluting stent and a paclitaxel-eluting stent in patients with coronary artery disease. One year clinical results. Gregg W. Stone. Presented at TCT 2009, San Francisco, USA. September 21–25, 2009.
____________________________________ From the Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, United Kingdom. The authors report no conflicts of interest regarding the content herein. Address for Correspondence: David Ramsdale, MD, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, United Kingdom. E-mail: David.Ramsdale@lhch.nhs.uk
