Novel DES with improved radiographic visibility noninferior to ultrathin-strut DES

Clemens von Birgelen

SAN DIEGO — A new zotarolimus-eluting stent designed to improve radiographic visibility while reducing strut thickness was noninferior to an ultrathin-strutted bioresorbable polymer-coated sirolimus-eluting stent, according to the BIONYX trial.

The BIONYX trial, which was presented at TCT 2018 by Clemens von Birgelen, MD, PhD, from Thoraxcentrum Twente and the University of Twente in the Netherlands, and simultaneously published The Lancet, was a randomized, assessor- and patient-blinded, noninferiority trial conducted at seven centers in Belgium, Israel and the Netherlands from 2015 to 2016. Patients were aged 30 to 96 years, 23.9% were women, 70.9% presented with ACS and 51.2% were treated for acute MI at enrollment.

Of 2,488 all-comer patients undergoing PCI with DES included in an intention-to-treat analysis, 1,243 were randomly assigned treatment with the novel ZES (Resolute Onyx, Medtronic) and 1,245 were assigned treatment with the SES (Orsiro, Biotronik).

Comparable outcomes

At 1 year, the primary endpoint of target vessel failure — a composite of cardiac death, target vessel-related MI or clinically driven target vessel revascularization — occurred in 4.5% of patients in the novel ZES group and 4.7% of patients in the SES group (HR = 0.75; 95% CI, 0.66-1.37). These data established the noninferiority, but not superiority, of the novel ZES compared with the SES (absolute risk difference, –0.2 percentage points; P for noninferiority = .0005; P for superiority = .77).

Additionally, at 1 year, the novel ZES was comparable to the SES in terms of cardiac death (1.1% vs. 0.6%; HR = 0.54; 95% CI, 0.21-1.34), target vessel-related MI (1.5% vs. 1.5%; HR = 1; 95% CI, 0.52-1.92) and clinically driven TVR (3.2% vs. 3.1%; HR = 1.02; 95% CI, 0.66-1.6).

There were also no significant differences between the novel ZES and SES groups in target lesion failure (cardiac death, target vessel MI or clinically indicated target lesion revascularization; P = .68), MACE (any death, any MI or clinically indicated TLR; P = .71) and the patient-oriented composite endpoint (any death, any MI or any revascularization; P = .41).

The researchers also observed no differences in antithrombotic therapy between the novel ZES and SES groups at hospital discharge. At 1 year, the only difference was greater use of triple therapy among patients treated with the novel ZES vs. the SES (1.1% vs. 0.4%; P = .04).

However, the incidence of definite or probable stent thrombosis was significantly lower with the novel ZES vs. the SES (0.1% vs. 0.7%; HR = 0.11; 95% CI, 0.01-0.87; log-rank P = .01).

“The novel Resolute Onyx stent was noninferior to the reference Orsiro stent for the primary endpoint of safety and efficacy. Secondary outcomes were favorable, representing a safety signal for both stents, and we observed a very low rate of stent thrombosis in the Resolute Onyx arm that warrants further clinical investigation,” von Birgelen said at TCT 2018.

Questioning noninferiority trials

The majority of contemporary stents use platforms from cobalt-chromium alloy, which has limited radiographic visibility, according to von Birgelen

“Suboptimal radiographic visibility can be challenging in obese patients, when treating bifurcated or calcified coronary lesions, or when carefully assessing stent apposition,” he said in a press release.

The novel ZES, which uses a novel thin-strut composite wire platform with a dense platinum-iridium core that allows reduced strut thickness and has a zotarolimus-eluting durable polymer coating, was developed in response to the demand for stents with improved visibility. The researchers opted to perform a head-to-head comparison of the novel ZES with the bioresorbable polymer-coated SES with an ultrathin cobalt-chromium strut platform because it has shown excellent safety and efficacy outcomes in other randomized trials, including BIOFLOW V, they wrote in The Lancet.

In an accompanying editorial comment, Edoardo Camenzind, MD, and Batric Popovic, MD, PhD, both from Institut Lorrain du Coeur et des Vaisseaux, CHU de Nancy, Universite de Lorraine in France, highlight common limitations of noninferiority trials and recommend interpreting the BIONYX trial results with caution.

“It is important to be aware that noninferiority trials are sensitive to many methodological issues that potentially affect the final results and are not powered to provide definitive information about safety, particularly when they are powered for a combined safety-efficacy endpoint. The stent thrombosis data from von Birgelen and colleagues’ study should be considered very carefully and warrant further investigation to identify possible causes, although the between-group differences are most likely due to chance,” they wrote. “For future comparative interventional trials, the inclusion of bleeding in the primary clinical endpoint should be considered to reflect current clinical realities and to enable reporting of all relevant events of importance to patients.” – by Melissa Foster

References:

von Birgelen C. Late-Breaking Trials 1. Presented at: TCT Scientific Symposium; Sept. 21-25, 2018; San Diego.

Camenzind E, et al. Lancet. 2018;doi:10.1016/S0140-6736(18)32334-1.

von Birgelen C, et al. Lancet. 2018;doi:10.1016/S0140-6736(18)32001-4.

Disclosures: The study was funded by Biotronik and Medtronic. Von Birgelen reports he has received institutional grant or research support from Abbott Vascular, Biotronik, Boston Scientific and Medtronic. Camenzind and Popovic report no relevant financial disclosures.

Editor's Note: This article was updated on Oct. 19, 2018 to correct an error in the headline. The Editors regret the error.