TAXUS-V ISR: Paclitaxel-Eluting Stents vs Vascular Brachytherapy for the Treatment of In-stent Restenosis Within Bare-Metal Stents

Luis Gruberg, MD, FACC

Disclosures

July 20, 2006

Editorial Collaboration

Medscape &

"The results of the TAXUS-V ISR trial are very important and provide us with supporting scientific data justifying the use of [drug-eluting stents] for the treatment of in-stent restenosis, a procedure that is common and has become the standard strategy in most catheterization laboratories around the world."

Presenter: Gregg W. Stone, MD (Columbia University Medical Center, New York, NY)

For many years, recurrent restenosis was the main limitation to bare-metal stents. Intravascular radiation therapy (brachytherapy) is still considered the gold standard of treatment, as it is the only therapeutic option approved by the US Food and Drug Administration. However, brachytherapy is no longer available in the majority of countries. Furthermore, it is a complex, time-consuming, and expensive therapy that requires prolonged dual-antiplatelet therapy. Due to limited availability of brachytherapy systems, drug-eluting stents (DES) have thus become the default therapy for patients with bare-metal stent in-stent restenosis. Until now, there have been no data regarding the safety and effectiveness of DES treatment in this setting, and a direct comparison between DES and brachytherapy has not been performed.

Study Design

The TAXUS V In-stent Restenosis (ISR)[1,2] trial was a multicenter, prospective, 1:1, open-label, randomized trial to evaluate the use of a paclitaxel-eluting stent (PES; Taxus, Boston Scientific, Natick, Massachusetts) vs brachytherapy for the treatment of in-stent restenosis within bare-metal stents.

Clinical follow-up was planned at 1, 4, and 9 months and then yearly for 5 years. Angiographic follow-up was performed at 9 months with a subgroup of 250 patients who underwent intravascular ultrasound.

Primary Endpoint

9-month ischemic target vessel revascularization, powered for sequential noninferiority and superiority.

Inclusion Criteria
  • Single target lesion in a native coronary artery;

  • Restenosis of a previously implanted bare-metal stent;

  • Target lesion length ≤ 46 mm; and

  • Reference vessel diameter ≥ 2.5 mm and ≤ 3.75 mm.

Exclusion Criteria
  • Non-study DES in target vessel;

  • Prior brachytherapy to target vessel;

  • Bifurcation lesion;

  • Previous myocardial infarction ≤ 72 hours; and

  • Left ventricular ejection fraction < 25%.

Results

Investigators randomized 396 patients with in-stent restenosis within a bare-metal stent to brachytherapy (n = 201) or PES (n = 195). The trial was originally designed to enroll a total of 500 patients, but was prematurely stopped due to lack of enrollment. Angiographic follow-up at 9 months was performed in 385 patients (97%).

With the exception of a higher rate of diabetes in PES-treated patients, other clinical characteristics were well balanced between the 2 groups (Table 1). Lesion characteristics were also similar; however, patients in the PES group had a significantly higher incidence of diffuse restenosis than that seen in patients in the brachytherapy group (Table 2).

Table 1. TAXUS V ISR: Baseline Clinical and Lesion Characteristics
Brachytherapy
(n = 201)
PES
(n = 195)
P
Age (yrs) 63 63 .6
Male (%) 70 62 .09
Diabetes (%) 30 40 .04
Insulin-treated (%) 10 20 .01
Hypercholesterolemia (%) 92 91 .8
Hypertension (%) 79 85 .2
Unstable angina (%) 28 28 .9
Table 2. TAXUS V ISR: Baseline Lesion Characteristics
Brachytherapy PES P
Reference vessel diameter (mm) 2.63 ± 0.46 2.68 ± 0.47 .3
Lesion length (mm) 17.4 ± 9.2 18.5 ± 9.5 .1
LAD lesion (%) 33 39 .2
Type C lesion (%) 44 44 .9
Focal type restenosis (%) 29 19 .02
Diffuse type restenosis (%) 47 61 .006
Proliferative (%) 24 19 .3
Total occlusion (%) 0.5 1 .6
LAD = left anterior descending; PES = paclitaxel-eluting stent

Brachytherapy was delivered via either the Beta-Cath (Novoste, Norcross, Georgia) or the Galileo (Guidant Corporation, Indianapolis, Indiana) systems for a median time of 198 seconds; 22 patients in this treatment arm received an additional stent. The 30-day event rate was low, with a 2.5% and 2.1% major adverse cardiac event rate in the brachytherapy and PES groups, respectively.

At 9-month angiographic follow-up, target lesion and target vessel revascularization rates were significantly higher in the intravascular brachytherapy arm compared with the PES arm, as were the rates of angiographic restenosis (31.2% vs 14.5%, respectively; P < .001) (Figures 1 and 2).

Figure 1. TAXUS V ISR: target lesion revascularization at 9-month follow-up.
Figure 2. TAXUS V ISR: target vessel revascularization at 9-month follow-up.

Mortality and myocardial infarction rates were low and similar in both groups. Stent thrombosis rates were also low and did not significantly differ between the brachytherapy and PES arms (2.6% vs 1.6%, respectively; P = .72). However, late loss in the analyzed segment was significantly lower in the PES arm (0.40 mm vs 0.29 mm; P < .001). The incidence rates of death, target vessel failure, and major adverse cardiac events all favored the PES group (Figure 3).

Figure 3. TAXUS V ISR: incidence of death, target vessel failure, and major adverse cardiac events at 9-month follow-up.
Conclusions

Compared with percutaneous coronary intervention with intravascular brachytherapy, treatment of bare-metal stent in-stent restenosis with PES is safe and provides superior efficacy.

Viewpoint

The results of the TAXUS-V ISR trial are very important and provide us with supporting scientific data justifying the use of DES for the treatment of in-stent restenosis, a procedure that is common and has become the standard strategy in most catheterization laboratories around the world. The use of DES for the treatment of in-stent restenosis within a bare-metal stent is a simple and very safe procedure, and as shown by the results from this study, is associated with good long-term results. Whether these results can be extrapolated to the small percentage of patients who develop in-stent restenosis of a DES remains to be seen, however.

References
  1. Stone GW, Ellis SG, O'Shaughnessy CD, et al. A prospective, multicenter, randomized trial evaluating the TAXUS paclitaxel-eluting coronary stent versus vascular brachytherapy for the treatment of bare metal stent in-stent restenosis: the TAXUS-V ISR trial. Program and abstracts from the Innovation in Intervention i2 Summit 2006; March 11-14, 2006; Atlanta, Georgia. Abstract 2402-9.

  2. Stone GW, Ellis SG, O'Shaughnessy CD, et al. Paclitaxel-eluting stents vs vascular brachytherapy for in-stent restenosis within bare-metal stents: the TAXUS V ISR randomized trial. JAMA. 2006;295:1253-1263. Abstract

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.

processing....