The Resolute Onyx polymer-based zotarolimus-eluting stent (ZES) had similar safety and effectiveness outcomes compared to the BioFreedom polymer-free biolimus A9-coated stent in high-bleeding-risk coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) in the final 2-year follow-up of the randomized Onyx ONE trial.
The findings follow those of the LEADERS FREE randomized trial, which showed that the BioFreedom drug-coated stent (DCS) was superior over bare metal stents in terms of safety and efficacy in high-bleeding-risk patients on short 1-month dual antiplatelet therapy regimens.
“While bare-metal stents had been favored over drug-eluting stents in the past given concerns of stent thrombosis (ST) in [high bleeding risk] patients treated with short-duration DAPT, current guidelines recommend contemporary drug-eluting stents irrespective of clinical and anatomic indications,” the researchers stressed.
A “considerable proportion” of symptomatic CAD patients undergoing treatment with PCI are at high risk for bleeding, the authors stressed, noting that guidelines from the American College of Cardiology/American Heart Association and European Society of Cardiology recommend DAPT for 1 to 6 months for these people.
The latest results of the Onyx ONE study – funded by Resolute Onyx manufacturer Medtronic – also support earlier 1-year findings from the trial, showing Resolute Onyx stents were non-inferior in safety and effectiveness to BioSensors Interventional Technologies’ BioFreedom stents in the same patients.
They were published Monday online, ahead of the June 13 issue of JACC: Cardiovascular Interventions, with authors led by Stephan Windecker, MD, from Bern University Hospital, Switzerland.
2-year Onyx ONE results
The Onyx ONE trial randomly assigned high-bleeding-risk patients to receive either ZES (1,003 patients) or DCS (993). The patients were treated with 1-month DAPT, followed by single antiplatelet therapy with either aspirin or a P2Y12 inhibitor for event-free subjects.
By 2 years, follow-up was completed in 980 (97.7%) of the ZES patients and 962 (96.9%) DCS patients.
At baseline, the patients were of similar age (a mean of 74 ± 9.5 years in ZES vs. 74.1 ± 9.8 years in DCS), and were similarly weighted in terms of sex (32.5% female vs. 34.2% female, respectively), body weight (a mean body mass index of 27.2 kg/m2 vs. 27.3 kg/m2), diabetic rates (38.7% vs. 38.5%) and hypertension rates (79.4% vs. 81.3%).
The primary safety endpoint – a composite of cardiac death, myocardial infarction or stent thrombosis – occurred in 208 ZES patients (21.2%) and 199 (20.7%) DCS patients (risk difference: 0.5%; 95% confidence interval [CI]: -3.1% to 4.2%; P = 0.78) at 2 years “without significant differences in individual components of the composite endpoint.”
Nevertheless, in an unadjusted analysis, all-cause mortality was more common among patients treated with ZES than DCS at 2 years (15.6% vs. 12.1%; 95% CI: 0.5 to 6.6; P = 0.03), which the researchers said was “due to numerically increased rates of both noncardiac and cardiac mortality.”
By multivariable analysis, chronic obstructive pulmonary disease, number of high-bleeding-risk criteria, diabetes and prior myocardial infarction were all independent risk factors for death at 2 years, the researchers added.
The secondary effectiveness endpoint – target lesion failure (the composite of cardiac death, target vessel myocardial infarction or clinically driven target lesion revascularization) – occurred in 217 (22.1%) of ZES patients and 202 (21%) DCS patients (risk difference: 1.1%; 95% CI: -2.5% to 4.8%; P = 0.54) at 2 years.
“Polymer-based ZES can be used safely in [high-bleeding-risk] patients treated with 1-month DAPT,” the authors concluded.
“Future studies will need to examine whether there are differences between stent types that may emerge beyond 2 years and which type of antiplatelet agent is most effective after discontinuation of DAPT.”
‘Clinically relevant distinction’ between polymer and polymer-free stents
In an accompanying editorial, Usman Baber, MD, MS, from the University of Oklahoma Health Sciences Center, noted that whether the salutary benefits conferred by a polymer-free DCS vs. a bare metal stent can extend to similar patients treated with durable-polymer drug-eluting stents (DES) has so far remained unclear.
This is despite the fact that durable-polymer DES remain the commonly used DES platforms in contemporary PCI.
“This distinction is clinically relevant for several reasons,” he said, noting that permanent polymers in first-generation DES have been linked with a prolonged inflammatory and thrombotic stimulus. This led to the development of DES with biodegradable or no polymer coatings in the first place, he said.
The “putative advantages” of polymer-free DES should also amplify over time, he said, “a relevant issue in [high-bleeding-risk] patents given the continued accrual of both ischemic and bleeding events with long-term follow-up.”
The current study addresses these evidence gaps, he said, branding it a “a welcome addition to the expanding armamentarium that we may offer complex patients at elevated bleeding risk.”
He stressed that the researchers’ observation of an unexpected nominal increase in all-cause mortality in ZES patients merits further scrutiny, but conceded: “A biologically plausible mechanism appears unlikely as 2-year rates of [myocardial infarction], definite or probable ST, and revascularization were comparable between groups.”
Baber went on to air hope that innovative technologies such as ultrathin-strut DES and next-generation resorbable scaffolds “may hold promise” for further incremental benefits over existing technologies in high-bleeding risk patients.
Windecker S, Latib A, Kedhi E, et al. Polymer-Based Versus Polymer-Free Stents in High Bleeding Risk Patients: Final 2-Year Results From Onyx ONE. JACC Cardiovasc Interv 2022;15:1153–1163.
Baber U. Polymer-Based Versus Polymer-Free Stents in High Bleeding Risk Patients: Less Is Not Always More. JACC Cardiovasc Interv 2022;15:1164-1166.
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