RIBS IV: EES Surpass DCB for Treatment of In-Stent Restenosis

In patients with DES restenosis, a second-generation everolimus-eluting stent (EES) produces better late angiographic outcomes than does a drug-coated balloon (DCB), according to results from the RIBS IV trial. An additional study suggests that when a DCB is used, early and late angiographic outcomes are poorer for restenosis occurring in a DES rather than in a BMS. 

Both papers were published in the July 7, 2015, issue of Journal of the American College of Cardiology.

For the RIBS IV trial, previously presented at TCT 2014, Fernando Alfonso, MD, PhD, of Hospital Universitario de la Princesa (Madrid, Spain), and colleagues randomized 309 patients with DES restenosis to receive the Xience Prime EES (Abbott Vascular; n = 155) or the SeQuent Please paclitaxel-coated balloon (B. Braun; n = 154) from January 2010 to August 2013. Baseline clinical and angiographic characteristics were similar between the 2 groups.

Angiographic success was 100%. Immediately after the procedure, acute lumen gain and final minimal lumen diameter (MLD) were larger and residual stenosis lower in the EES group compared with the DCB group.

At 6- to 9-month follow-up (median 247 days), in-segment MLD (primary endpoint) was larger with EES. Lesions treated with an EES rather than with a DCB also had greater net lumen gain and lower percent diameter stenosis and binary restenosis. Data were similar for in-lesion analyses.

Analysis of the primary endpoint using 10 prespecified variables showed that the advantage for EES was consistent across subgroups. 

The primary clinical outcome measure (cardiac death, MI, and TVR) was lower in the EES arm than in the DCB arm at 1 year (10% vs 18%; P = .04), mostly driven by a 50% reduction in TVR (8.4% vs 16.2%; P = .03). There were no differences between groups for rates of definite stent thrombosis, MI, cardiac death, or all-cause mortality.   

Better Acute Procedural Success

“Notably, the superior late angiographic findings of EES were consistent using both in-segment and in-lesion analyses, suggesting that final results were not affected by edge-related problems,” Dr. Alfonso and colleagues write.  

Additionally, they say, the study demonstrates that the advantage of the EES over the DCB stems partially from better acute procedural results, a finding that has been shown in previous studies, including ISAR-DESIRE 3 and RIBS V.

According to the study authors, DCBs are an attractive option for patients presenting with several stent layers at the target site as well as for those with relatively large side branches emerging from the stent, those unable to take prolonged dual antiplatelet therapy, and those at high bleeding risk.

“Further studies are required to unravel the subsets of patients with DES [in-stent restenosis] who benefit from the use of [DCBs],” they say.

DCB Does Better When Restenosis in BMS vs DES

For the second study, Seiji Habara, MD, of Kurashiki Central Hospital (Kurashiki, Japan), and colleagues looked at long-term safety and efficacy outcomes for 468 patients (550 lesions with in-stent restenosis) treated at their institution with the SeQuent Please DCB between September 2008 and December 2012.

In all, 114 cases of restenosis occurred in a BMS and 436 occurred in a DES. In the latter group, 42.9% of affected lesions were originally treated with a stent that eluted sirolimus, 18.6% everolimus, 14.0% paclitaxel, 13.1% zotarolimus, and 11.5% biolimus.

At 6-month angiographic follow-up, the TLR rate of patients originally treated with a DES was nearly twice that of those treated with a BMS (13.9% vs 7.0%; P = .002). Furthermore, at 18- to 24-month angiographic follow-up, the rate of late restenosis was much lower in patients with restenosis in BMS compared with in DES (2.5% vs 16.8%; P < .001), as was percent diameter stenosis at both 6- and 18-month follow-up. BMS-treated lesions also had less delayed late lumen loss.

Altogether, these differences translated to a nearly 3-fold greater rate of TLR for those with DES in-stent restenosis at long-term angiographic follow-up (24.2% vs 8.7%; Log rank P = .003). There were no differences in rates of late restenosis, TLR, or delayed late lumen loss between lesions that received first-generation vs second-generation DES.

No differences were seen between groups for the composite of cardiac death, MI, or target lesion thrombosis at 24 months (log rank P = .8). Previous stent size ≤ 2.5 mm, postprocedural percent diameter stenosis, and in-stent occlusion lesion independently predicted early restenosis, while previous treatment with DES, percent diameter stenosis at early follow-up, and hemodialysis predicted late restenosis.

Hope for a Limus DCB?  

In an accompanying editorial, Antonio Colombo, MD, and Neil Ruparelia, MBBS, DPhil, of San Raffaele Scientific Institute (Milan, Italy), say the 2 studies suggest that DCB treatment may only be appropriate in specific subsets of patients with in-stent restenosis.

However, given that a paclitaxel-coated balloon is the only current choice, they say the potential for a balloon coated with sirolimus could change the situation.

Additionally, the editorialists suggest, another option for treating in-stent restenosis of DES is bioresorbable scaffolds, “which theoretically would achieve excellent acute gain without the potential long-term consequences of an additional metal layer in the vessel wall.” Also to be considered is whether it is possible to identify restenotic lesions for which DCBs would be equivalent or superior to EES.

For now, Drs. Colombo and Ruparelia say, the available evidence suggests that while EES can safely and effectively treat in-stent restenosis of DES, the potential of DCBs for this indication is limited.

“While awaiting new data, the strategy of stenting a stent, even if not perceived as particularly elegant, should be the default approach for most lesions presenting with DES restenosis,” they conclude.

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Sources:

1. Alfonso F, Pérez-Vizcayno MJ, Cárdenas A, et al. A prospective randomized trial of drug-eluting balloons versus everolimus-eluting stents in patients with in-stent restenosis of drug-eluting stents: the RIBS IV randomized clinical trial. J Am Coll Cardiol. 2015;66:23-33. 
2. Habara S, Kadota K, Shimada T, et al. Late restenosis after paclitaxel-coated balloon angioplasty occurs in patients with drug-eluting stent restenosis. J Am Coll Cardiol. 2015;66:14-22.
3. Colombo A, Ruparelia N. Is a drug-eluting stent the default treatment strategy for drug-eluting stent restenosis [editorial]? J Am Coll Cardiol. 2015;66:34-36.  

Disclosures:

• RIBS IV was sponsored by an unrestricted grant from Abbott Vascular and B. Braun Surgical. 
• Drs. Alfonso, Habara, Colombo, and Ruparelia report no relevant conflicts of interest.