Randomized Comparison of Ridaforolimus- and Zotarolimus-Eluting Coronary Stents in Patients With Coronary Artery Disease: Primary Results From the BIONICS Trial (BioNIR Ridaforolimus-Eluting Coronary Stent System in Coronary Stenosis)

Abstract

Background: The safety and efficacy of a novel cobalt alloy-based coronary stent with a durable elastomeric polymer eluting the antiproliferative agent ridaforolimus for treatment of patients with coronary artery disease is undetermined.

Methods: A prospective, international 1:1 randomized trial was conducted to evaluate in a noninferiority design the relative safety and efficacy of ridaforolimus-eluting stents (RESs) and slow-release zotarolimus-eluting stents among 1919 patients undergoing percutaneous coronary intervention at 76 centers. Inclusion criteria allowed enrollment of patients with recent myocardial infarction, total occlusions, bifurcations lesions, and other complex conditions.

Results: Baseline clinical and angiographic characteristics were similar between the groups. Overall, mean age was 63.4 years, 32.5% had diabetes mellitus, and 39.7% presented with acute coronary syndromes. At 12 months, the primary end point of target lesion failure (composite of cardiac death, target vessel-related myocardial infarction, and target lesion revascularization) was 5.4% for both devices (upper bound of 1-sided 95% confidence interval 1.8%, P_{noninferiority}=0.001). Definite/probable stent thrombosis rates were low in both groups (0.4% RES versus 0.6% zotarolimus-eluting stent, P=0.75); 13-month angiographic in-stent late lumen loss was 0.22±0.41 mm and 0.23±0.39 mm (P_{noninferiority}=0.004) for the RES and zotarolimus-eluting stent groups, respectively, and intravascular ultrasound percent neointimal hyperplasia was 8.10±5.81 and 8.85±7.77, respectively (P_{noninferiority}=0.01).

Conclusions: In the present trial, which allowed broad inclusion criteria, the novel RESs met the prespecified criteria for noninferiority compared with zotarolimus-eluting stents for the primary end point of target lesion failure at 12 months and had similar measures of late lumen loss. These findings support the safety and efficacy of RESs in patients who are representative of clinical practice.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01995487.

Keywords: coronary intervention; drug-eluting stent; percutaneous; ridaforolimus; stent thrombosis.

Figure 1. BIONICS trial (BioNIR Ridaforolimus Eluting Coronary Stent System in Coronary Steno-sis) flow chart

Full analysis set included all randomized subjects assigned to treatment per randomization regardless of whether they received the study stent. Subjects were included for analysis once the study stent had been advanced beyond the guide catheter. IVUS indicates intravascular ultrasound.

Figure 2. One-year target lesion failure

Kaplan-Meier estimates of the primary outcome target lesion failure by 1 year. CI indicates confidence interval, and HR, hazard ratio.

Figure 3. Subgroup analysis for the primary end point of target lesion failure at 1-year follow-up

Subgroup analysis for prespecified baseline characteristics is shown. The P value for qualitative interaction (treatment by subgroup) is obtained from the Gail-Simon test, which assesses the heterogeneity of the treatment effect across subgroups. ACS indicates acute coronary syndrome; CI, confidence interval; RES, ridaforolimus-eluting stent; TLF, target lesion failure; and ZES, zotarolimus-eluting stent.