Onyx ONE: Shorter DAPT Plus ZES Noninferior to Polymer-Free Stent in High-Bleeding-Risk Patients

SAN FRANCISCO, CA—In PCI patients at high risk for bleeding, a polymer-based DES combined with 1-month dual antiplatelet therapy (DAPT) is noninferior to a polymer-free drug-coated stent combined with the same DAPT regimen, and may confer better angiographic outcomes, the Onyx ONE trial suggests.

The study, presented in a late-breaking trial session at TCT 2019, adds to prior data from the LEADERS-FREE trial, which showed better safety and efficacy of polymer-free biolimus-A9-coated stents over otherwise identical BMS in high-bleeding-risk patients receiving a short 1-month duration of DAPT.

Onyx ONE, headed by Stephan Windecker, MD (Swiss Cardiovascular Center, Bern, Switzerland), found that for the primary composite safety endpoint of cardiac death, MI, and definite/probable stent thrombosis at 1 year, the Resolute Onyx zotorolimus-eluting stent (ZES) was noninferior to the drug-coated BioFreedom stent (17.1% vs 16.9%; P = 0.011), with a risk difference of 0.2% and a one-sided upper-bound 95% CI of 3%.

There were no differences between the stents for the combined secondary effectiveness endpoint of TLF at 1 year. Event rates were driven by similar rates of target-vessel MI in both groups (12.8% for Resolute Onyx vs 14.0% for BioFreedom; P = 0.43). However, landmark analysis revealed a significantly lower incidence of target-vessel MI with the ZES (3.7% vs 5.9%; P = 0.02).

Speaking in a press conference prior to the presentation, panelist Marco Valgimigli, MD, PhD (University of Bern, Switzerland), said the study “for the very first time allows us to know that the Onyx stent is a very viable and reasonable option."

Polymer-free stents were initially developed out of hopes that, without the polymer, the risk of stent thrombosis would be lower, thus allowing DAPT durations to be shortened. But the new data, combined with those of similar trials, seems to question whether going polymer free is really necessary.

Sripal Bangalore, MD (NYU Langone Medical Center, New York, NY), who was not involved in the study, told TCTMD that given the fact that BMS have now largely gone out of use in most US clinical practice, the results are reassuring for the high-bleeding-risk population.

And rather than showing that polymer-free devices are the way of the future, in fact Onyx ONE suggests the reverse: that perhaps durable-polymer DES are doing just fine. “This again proves the point that current durable, biocompatible-polymer DES have low thrombogenicity, and questions the role of the bioabsorbable-polymer DES or polymer-free ones,” he said in an email. “We really need to ask if we should be paying more for the latter stents.”

Event Rates Driven by MI

Onyx ONE randomized 2,000 patients who were at high bleeding risk and scheduled to undergo PCI to either Resolute Onyx ZES (Medtronic) or BioFreedom polymer-free biolimus A9-coated stent (Biosensors). The study was carried out at 84 centers in 23 countries where both stents were commercially available. Patients were elderly (mean age 74 years); approximately 40% in each group were diabetic and 50% had ACS. The most common reason for high-bleeding risk was age over 75 years and oral anticoagulant use.

The rate of crossover to the other stent was highest for the BioFreedom group. Forty patients in that group crossed over to Resolute Onyx whereas only two patients assigned to Resolute Onyx crossed over to BioFreedom. Device and procedural success were similar in both stent groups. However, there was a non-significantly greater percentage of device success in the Resolute Onyx group driven by improved angiographic outcomes compared with BioFreedom in terms of diameter stenosis and acute gain, both in-stent and in-segment.

At 1 month postprocedure, 92.5% of patients were on DAPT. By 2 months, 92% had transitioned to monotherapy consisting of aspirin in 56% and a P2Y12 inhibitor in 44%. At 12 months, 88% remained on a single antithrombotic therapy.

Cumulative incidence curves for the primary safety endpoint were converged at 1 year at 17.3% (HR 1.02; 95% CI 0.83-1.27). Windecker noted that event rates were largely driven by MI, which occurred in 15% of the BioFreedom group and 13.5% of the Resolute Onyx group (P = 0.50). Cardiac death was low and comparable in both groups (4.6% for Resolute Onyx vs 3.9% for BioFreedom; P = 0.40). Rates of definite/probable stent thrombosis were 2.2% with BioFreedom and 1.5% with Resolute Onyx (P = 0.21).

Analysis of MI events found that while periprocedural MI was comparable in both arms (P = 0.26), the BioFreedom group had a significantly higher rate of spontaneous MI at 1 year compared with Resolute Onyx (7.1% vs 4.6%; P = 0.02). Additionally, in landmark analysis by time of DAPT discontinuation, rates of MI were lower at 1 year with Resolute Onyx than with BioFreedom (4.3% vs 6.8%; P = 0.01).

Not surprisingly, bleeding rates were high in both groups, but they were not statistically different for any BARC category.

Is 1 Month Truly Enough?

Onyx ONE has some considerable limitations, including being a single-blinded trial that was not powered for low-frequency events and lacked a longer-duration DAPT control arm.

To TCTMD, Bangalore noted that the 1-year rate of stent thrombosis in both arms is high in the context of other trials in this patient population. For instance, in the STOPDAPT-2 trial using a fluoropolymer everolimus-eluting stent in a cohort at high bleeding risk, the stent thrombosis (ST) rate fell below 0.3%, he observed. “One wonders if the data is as reassuring as one would think and is left to wonder if there would have been a lower rate of ST and other ischemic outcomes if there was a 3- to 6-month DAPT comparator arm.”

Addressing this in the press conference, Windecker said it is an important point, but noted that it is unclear if the lower event rates might be related to different genetics in the all-Asian population of STOP-DAPT, or possibly to systematic routine use of IVUS.

“Nevertheless, 2% at 1 year is probably double as much as we would expect,” he said. “It echoes what was seen in LEADERS-FREE. It’s pretty much the same rate of 2%.”

Windecker added that early stent thrombosis rates in Onyx ONE were numerically lower with the ZES compared with the drug-coated stent at 0.6% versus 1.3%. Still, he said, it does raise the issue of “whether 1 month of DAPT is truly the optimal balance between safety and efficacy in this patient population.”