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.

Background: Treatment of patients with drug-eluting stent (DES) in-stent restenosis (ISR) remains a major challenge.

Objectives: This study evaluated the comparative efficacy of drug-eluting balloons (DEB) and everolimus-eluting stents (EES) in patients presenting with DES-ISR.

Methods: The study design of this multicenter randomized clinical trial assumed superiority of EES for the primary endpoint, in-segment minimal lumen diameter at the 6- to 9-month angiographic follow-up.

Results: A total of 309 patients with DES-ISR from 23 Spanish university hospitals were randomly allocated to DEB (n = 154) or EES (n = 155). At late angiography (median 247 days; 90% of eligible patients), patients in the EES arm had a significantly larger minimal lumen diameter (2.03 ± 0.7 mm vs. 1.80 ± 0.6 mm; p < 0.01) (absolute mean difference: 0.23 mm; 95% CI: 0.07 to 0.38) [corrected], net lumen gain (1.28 ± 0.7 mm vs. 1.01 ± 0.7 mm; p < 0.01), and lower percent diameter stenosis (23 ± 22% vs. 30 ± 22%; p < 0.01) and binary restenosis rate (11% vs. 19%; p = 0.06), compared with patients in the DEB arm. Consistent results were observed in the in-lesion analysis. At the 1-year clinical follow-up (100% of patients), the main clinical outcome measure (composite of cardiac death, myocardial infarction, and target vessel revascularization) was significantly reduced in the EES arm (10% vs. 18%; p = 0.04; hazard ratio: 0.58; 95% CI: 0.35 to 0.98), mainly driven by a lower need for target vessel revascularization (8% vs. 16%; p = 0.035).

Conclusions: In patients with DES-ISR, EES provided superior long-term clinical and angiographic results compared with DEB. (Restenosis Intra-Stent of Drug-Eluting Stents: Drug-Eluting Balloon vs Everolimus-Eluting Stent [RIBS IV]; NCT01239940).