ISAR-DESIRE 3 Published: Paclitaxel-Eluting Balloons Match PES for DES Restenosis
Paclitaxel-eluting balloons (PEB) are just as effective at treating restenosis that develops after limus-eluting stent implantation as paclitaxel-eluting stents (PES). Both options, however, are better at preventing repeat narrowing than balloon angioplasty alone, according to a paper published in the February 9, 2013, issue of the Lancet.
Findings from the ISAR-DESIRE 3 trial were previously presented at the annual Transcatheter Cardiovascular Therapeutics scientific symposium in October 2012 in Miami, FL.
Robert A. Byrne, MB, BCh, PhD, of Deutsches Herzzentrum (Munich, Germany), and colleagues enrolled 402 patients at 3 centers between 2009 and 2011. All had developed at least 50% restenosis after receiving a limus-eluting stent (n = 500 vessels). At each center, patients were randomized to receive the SeQuent Please PEB (B Braun, Melsungen, Germany; n = 137), Taxus Liberté PES (Boston Scientific, Natick, MA; n = 131), or balloon angioplasty (n = 134).
Protocol-mandated angiographic follow-up was obtained at 6 to 8 months in 338 patients (84%) with 466 vessels (93.2%). PEB proved noninferior to PES for the primary endpoint of diameter stenosis (P for noninferiority = 0.007), while both paclitaxel-eluting devices were superior to balloon angioplasty (P < 0.0001). Other measures such as minimal lumen diameter, recurrent binary restenosis, and late lumen loss showed similar patterns (table 1). Per-protocol analysis did not change the results.
Table 1. Angiographic Follow-up at 6 to 8 Months: Per-Lesion Analysis
|
PEB |
PES |
Balloon Angioplasty |
Diameter Stenosis |
38.0% |
37.4% |
54.1% |
Minimal Lumen Diameter, mm |
1.29 |
1.82 |
1.26 |
Recurrent Binary Restenosis |
27% |
24% |
57% |
Late Lumen Loss, mm |
0.37 |
0.34 |
0.70 |
In patients treated with either paclitaxel-eluting device, diameter stenosis did not differ by restenosis morphology at baseline. Nor was there any interaction between PEB vs. PES treatment and outcome according to age, sex, diabetes, or vessel size.
In Kaplan-Meier estimates at 1 year, most clinical outcomes were similar among the 3 treatment arms. TLR rates were statistically similar for the PEB and PES groups (P = 0.09) but higher for balloon angioplasty compared with either paclitaxel-eluting device (P < 0.0001 for both comparisons; table 2).
Table 2. Clinical Follow-up at 1 Year: Per-Patient Analysis
|
PEB |
PES |
Balloon Angioplasty |
Death |
2.2% |
4.6% |
5.3% |
MI |
2.1% |
2.4% |
1.5% |
Target Lesion Thrombosis |
0.7% |
0.8% |
0 |
TLR |
22.1% |
13.5% |
43.5% |
Based on the current results, PEB may be an alternative to PES in this clinical scenario, the investigators conclude. In addition, they note, “the superiority of both PEB and PES to balloon angioplasty in our study suggests that angioplasty alone has a restricted role, at least as a default treatment strategy for these patients.”
The paper adds that the reduction in late loss with PEB over angioplasty alone “provides further evidence to support the validity of the notion that a brief (typically 60 [-second]) dilation with a drug-eluting balloon results in sustained suppression of neointimal hyperplasia in the medium term.”
In an e-mail communication with TCTMD, Dr. Byrne said, “The logical conclusion [of ISAR-DESIRE 3] is that all other things being equal, the patient can be spared further unnecessary stent implantation.”
He added, however, that “it is important to remember that there will of course be individual cases where plain angioplasty alone might be the best option (eg, isolated significant stent underexpansion).”
The randomized ISAR-DESIRE 4 trial is “now testing the hypothesis that, when treating restenosis with [drug-eluting balloons], lesion preparation with a cutting balloon will confer enhanced [drug-eluting balloon efficacy],”Dr. Byrne reported. “We expect to have data from this study in the latter half of 2014.”
Broad Adoption of PEB Not a Done Deal
In an accompanying editorial, Fernando Alfonso, MD, PhD, and María J. Pérez-Vizcayno, MD, both of Clinico San Carlos University Hospital (Madrid, Spain), predict that “most clinicians will conclude that PEB are the clear winners [in the current study]. By removing the need for an additional stent layer, drug-eluting balloons might become the treatment of choice for restenosis after implantation of DES.”
Studies are underway looking at how second-generation DES might change the equation, they point out, also stressing that a class effect for drug-eluting balloons cannot be assumed.
“Broad adoption [of drug-eluting balloons] will necessitate large studies with clinical endpoints” as well as exploration of the technology “in diverse situations,” Drs. Alfonso and Pérez-Vizcayno note, adding, “Use of drug-eluting balloons will be challenging for young clinicians who have never been trained to optimize results of balloon angioplasty.”
Technique Is Important
Bruno Scheller, MD, of the University of Saarland (Homburg, Germany), pointed out to TCTMD in an e-mail communication that so far 6 randomized controlled trials have shown the efficacy of PEB in treating in-stent restenosis: PACCOCATH ISR I and II, PEPCAD II, DES-ISR, PEPCAD-DES, and now ISAR-DESIRE 3.
Among them, ISAR-DESIRE 3 showed the most late loss and need for TLR with PEB, a finding perhaps explained by the fact that “careful lesion preparation before [drug-coated balloon] use was mandatory in all [the other] randomized trials,” Dr. Scheller said. This may in fact be why PEB failed to show superiority over PES in ISAR-DESIRE 3 as they had in treating BMS restenosis in PEPCAD II, he suggested.
“Nevertheless, [PEB] are preferable” for treating DES and BMS restenosis, Dr. Scheller concluded, “due to the avoidance of an additional layer of metal and a shortened dual antiplatelet therapy.”
As to how the ISAR-DESIRE 3 results might hold up over the long-term, he cited evidence from PACCOCATH ISAR I and II as well as from PEPCAD II showing “sustained benefit” with drug-coated balloons at 5 and 3 years, respectively.
Sources:
1. Byrne RA, Neumann F-J, Mehilli J, et al. Paclitaxel-eluting balloons, paclitaxel-eluting stents, and balloon angioplasty in patients with restenosis after implantation of a drug-eluting stent (ISAR-DESIRE 3): A randomised, open-label trial. Lancet. 2013;381:461-467.
2. Alfonso F, Pérez-Vizcayno MJ. Drug-eluting balloons for restenosis after stent implantation. Lancet. 2013;381:431-433.
Related Stories:
Caitlin E. Cox is News Editor of TCTMD and Associate Director, Editorial Content at the Cardiovascular Research Foundation. She produces the…
Read Full BioDisclosures
- Drs. Byrne, Alfonso, and Pérez-Vizcayno report no relevant conflicts of interest.
- Dr. Scheller reports serving as a co-inventor of patent applications for various methods of restenosis inhibition including drug-eluting balloons. He is a shareholder of InnoRa GmbH and has received lecture fees from B Braun and Medtronic.
Comments