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Both drug-eluting balloons (DEB) and everolimus-eluting stents (EES) are excellent options for treating patients with bare metal stent (BMS) restenosis and result in low recurrence rates, according to a study published online January 8, 2014, ahead of print in the Journal of the American College of Cardiology. While treatment with EES demonstrated superior efficacy on late angiography compared with DEB, clinical relevance remains unknown.

For multicenter RIBS V (Restenosis Intra-stent: Drug-eluting Balloon vs. everolimus-eluting Stent) trial, Fernando Alfonso, MD, of the Hospital Universitario de La Princesa (Madrid, Spain), and colleagues randomized 189 patients with BMS in-stent restenosis to treatment with a paclitaxel-eluting balloon (SeQuent Please, B. Braun Surgical, Melsungen, Germany; n = 95) or an EES (Xience Prime, Abbott Vascular, Santa Clara, CA; n = 94).

Those treated with EES showed increased post-procedure benefit in terms of minimal lumen diameter (MLD), residual stenosis, and acute gain compared with drug-eluting balloons. Late angiographic studies obtained at a median of 249 days (n = 170) demonstrated larger in-segment MLD, lower percentage diameter stenosis, and greater net lumen gain with EES compared with drug-eluting balloons. Restenosis was similar for both cohorts (table 1).

Table 1. In-segment Angiographic Results

After adjusting for age, diabetes, smoking, and percentage diameter stenosis, differences in MLD still favored EES (absolute mean difference 0.29; 95% CI 0.18-0.55; P < 0.001). However, paclitaxel-eluting balloon and EES patients experienced similar angiographic late loss (0.14 ± 0.5 vs. 0.04 ± 0.5 mm, P = 0.14) and binary restenosis (9.5% vs. 4.7%; P = 0.22).

In the drug-eluting balloon and EES groups, 1-year rates of freedom from cardiac death, MI, and TVR (8% vs. 6%; HR 0.76; 95% CI 0.26-2.18, P = 0.6) and TVR (6% vs. 2%; HR 0.32; 95% CI 0.07-1.59, P = 0.17) were similar.

“Our study was unable to find differences in the composite clinical outcome measure and was largely underpowered to detect differences in individual events, including repeat revascularization,” the study authors write. “Nevertheless, we cannot exclude that the superior angiographic findings obtained with EES might eventually translate into a clear net clinical benefit.”

Highly Effective Interventions Available

BMS in-stent restenosis used to be considered a challenging condition with a high rate of clinical and angiographic recurrence after balloon angioplasty, Dr. Alfonso told TCTMD in an e-mail communication. Researchers then discovered that first-generation DES and drug-eluting balloons could successfully treat the condition. “Now, we know that both [drug-eluting balloons] and second-generation DES, specifically the everolimus-eluting stent in this study, provide excellent long-term clinical and angiographic results in this setting,” he said.

In an e-mail communication with TCTMD, Bruno Scheller, MD, of the University of Saarland (Homburg, Germany), said based on this study, both EES and drug-eluting balloons lead to single digit binary restenosis rates and event-free survival rates of more than 90% at 1 year.

Balloons Still Preferable

Second-generation DES have impressive antiproliferative effects coupled with a unique safety record, which explains their high efficacy in patients with BMS in-stent restenosis, Dr. Alfonso explained. “However, I still believe that [drug-eluting balloons] may be considered as a very good first-line treatment for these patients.” He added that many studies, including the current trial, support the value of these devices.

Overall, RIBS V complements other research supporting the use of drug-eluting balloons for in-stent restenosis, Dr. Scheller concluded. Advantages of the technology, which outweigh the small angiographic but clinically irrelevant benefit of EES, include the avoidance of another layer of metal, procedure repeatability, and shortened dual antiplatelet therapy, he noted.

Additionally, other technologies such as fully bioresorbable scaffolds are unlikely to outperform the safety and efficacy of drug-eluting balloons. “Therefore, [drug-eluting balloons] should become the first-line treatment [for] in-stent restenosis,” Dr. Scheller commented.

Significance of Superior Angiographic Findings

Why superior angiographic findings for EES did not translate to a net clinical benefit is not fully understood, Dr. Alfonso said. However, the study was not powered to detect differences in clinical endpoints. Any reduction in TVR may have been detected with a larger number of patients or with a longer clinical follow-up, he explained, adding that “all patients in RIBS V will be systematically followed-up after 1 year to address this possibility.”

Superior angiographic findings for the EES group at follow-up can be attributed to better initial lumen gain, Dr. Scheller observed. Nevertheless, the angiographic findings in the drug-eluting balloon group were also excellent. “This may explain why there was no better long-term clinical outcome with EES as compared with [drug-eluting balloons],” he said.

Longer clinical follow-up of both strategies is needed to confirm current findings beyond the first year, Dr. Alfonso stated. Also of note, DES in-stent restenosis is more challenging to treat than that with BMS. Therefore, results of the next RIBS trial, in which patients with DES in-stent restenosis are randomized to drug-eluting balloons or EES, are eagerly awaited, he concluded.

Alfonso F, Pérez-Vizcayno MJ, Cárdenas A, et al. A randomized comparison of drug-eluting balloon versus everolimus-eluting stent in patients with bare-metal stent in-stent restenosis: The RIBS V Clinical Trial. J Am Coll Cardiol. 2014;Epub ahead of print.

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