Gregg W. Stone, M.D., of Columbia University Medical Center, New York, and colleagues with the TAXUS V ISR trial compared the use of paclitaxel-releasing stents with vascular brachytherapy (VBT – radiation therapy) in patients with in-stent restenosis (ISR – renarrowing of an artery after treatment) of bare-metal stents.
According to background information in the article, VBT is the only U.S. Food and Drug Administration (FDA)-approved treatment for bare-metal coronary ISR; however, VBT is logistically complex, expensive, and associated with late thrombosis and restenosis. These limitations have resulted in a shift away from VBT for treatment of ISR in daily clinical practice despite the absence of a proven therapeutic alternative. Restenosis occurs in 10 percent to 50 percent or more of patients following implantation of bare-metal stents. Drug-eluting (releasing) stents have been demonstrated to safely reduce restenosis compared with bare-metal stents. Whether drug-eluting stents are safe and effective for treatment of ISR, however, has not been established.
The multicenter randomized trial included 396 patients with in-stent restenosis of a previously implanted bare-metal coronary stent. The study was conducted between June 2003, and July 2004 at 37 North American academic and community-based institutions. Patients were randomly assigned to undergo angioplasty followed by VBT (n = 201) or paclitaxel-releasing stent implantation (n = 195). Clinical and angiographic follow-up at 9 months were scheduled in all patients.
Implantation of paclitaxel-eluting stents compared with VBT significantly reduced the 9-month rate of ischemic target vessel revascularization by 40 percent. The rate of ischemic target lesion revascularization at 9 months was 6.3 percent with the paclitaxel-eluting stent compared with 13.9 percent for VBT, a relative risk reduction of 55 percent. Relative reductions in total target lesion (61 percent) and target vessel (49 percent) revascularization events were higher after treatment with the paclitaxel-eluting stent rather than VBT when only ischemic related events were considered. Paclitaxel-eluting stents reduced the 9-month composite rate of major adverse cardiac events by 43 percent compared with VBT. Patients with paclitaxel-eluting stents had a 53 percent lower rate of angiographic restenosis at 9 months, compared with VBT.
"The results from this trial in concert with other studies, indicate that drug-eluting stents should now be considered the treatment of choice for most patients with ISR of previously implanted bare-metal stents. Paclitaxel-eluting stents significantly reduce clinical and angiographic restenosis and improve event-free survival compared with beta-source intracoronary radiation. For patients with bare-metal stents who develop in-stent restenosis, the availability of drug-eluting stents represents a safe therapy resulting in a high rate of 9-month event-free survival, a reassuring option for an otherwise difficult-to-treat cohort of patients. Further studies are required to demonstrate the long-term safety and durability of this approach," the authors conclude.
(JAMA. 2006;295:1253-1263. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: This study was sponsored and funded by Boston Scientific Corp., Natick, Mass. For the financial disclosures of the authors, please see the JAMA article.
Editorial: Brachytherapy for In-Stent Restenosis - A Distant Second Choice to Drug-Eluting Stent Placement
In an accompanying editorial, Debabrata Mukherjee, M.D., and David J. Moliterno, M.D., of the University of Kentucky, Lexington, comment on the studies comparing drug-eluting stents with VBT.
" … the next major question may shift focus from the optimal strategy for ISR within bare-metal stents to that occurring within drug-eluting stents. It is doubtful that brachytherapy will have a tenable role in the treatment of drug-eluting stent restenosis. Rather, head-to-head trials of drug-eluting stent–in–drug-eluting stent (with the same vs. a different antiproliferative agent) will be needed. Given the low expected rate of subsequent target vessel revascularization, it is plausible that such a trial will need to be quite large and take into account other questions, such as the long-term durability of drug-eluting stents for treating ISR, safety of local reapplication of antiproliferative agents, and optimal duration of dual-antiplatelet therapy."
(JAMA. 2006;295:1307-1309. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: Dr. Moliterno has served on data and safety monitoring committees for stent manufacturers, including Boston Scientific and Guidant. Dr. Mukherjee reported no financial disclosures.
Journal
JAMA