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Two-Year Results from Onyx ONE Trial: No Difference Between Onyx DES and BioFreedom DCS
-- The Hypothesis That a Polymer-Free Stent Would Be Superior to the Latest Generation DES for High Bleeding Risk Patients After Only One Month of DAPT Was Disproved
-- However, Both Types of Stents Have Proven Superiority to Bare Metal Stents
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Medtronic's Onyx Drug-Eluting Stent (DES)
Medtronic's Onyx Drug-Eluting Stent (DES)
June 9, 2022 -- The final two-year results of the Onyx ONE randomized controlled trial were just published in JACC: Interventions. The trial studied patients who were at high risk for bleeding; so they received only one month of dual antiplatelet therapy (DAPT), followed by single antiplatelet therapy. The results, consistent with the outcomes seen at one year, showed that at two years there was no difference between patients who received the Onyx permanent polymer drug-eluting stent (DES), made by Medtronic, and those who received the BioFreedom polymer-free drug-coated stent (DCS), made by Biosensors.

Background to Dual Antiplatelet Therapy After Drug-Eluting Stents
The first generation of drug-eluting stents were introduced two decades ago. For most of the previous decade, only bare metal stents (BMS) were used. They were successful in virtually eliminating the problem of abrupt closure of a coronary artery after balloon inflation, an event which necessitated emergency bypass surgery in approximately 5% of cases. As stent pioneer, Dr. Gary Roubin, has said" "Stents made angioplasty safer."

BMS also reduced the high restenosis (re-narrowing) rates of 30-40% seen with balloon-only angioplasty, but they still suffered restenosis rates of 20-25%, due to the growth of cells in and around the implanted stent, even though antiplatelet drugs were used immediately post-procedure and continued for a month or two.

In response to these problems, the drug-eluting stent was devised: a polymer-coated stent that over time would elute a drug, initially paclitaxel or sirolimus, to inhibit the growth of cells and therefore reduce the restenosis rate. It was estimated that six months of dual antiplatelet therapy (DAPT -- usually aspirin plus clopidogrel) still was critically important to avoid stent thrombosis. Again, these new devices did indeed reduce the restenosis rates, down to single digits. But at the European Congress of Cardiology in 2006, reports surfaced that there was a risk of late stent thrombosis (ST) with drug-eluting stents, after the six-month period, something not seen with bare-metal stents. It was determined that the polymer on the stents may be the contributing factor to this complication. These reports resulted in recommendations to increase the period of dual antiplatelet therapy to one year, at the minimum.

A problem, however, existed in that a not insignificant portion of patients who needed stents were also at high bleeding risk (HBR), a situation exacerbated by a year of DAPT, a serious side-effect of which is bleeding. So for those HBR patients, or for any patients who might not be able to tolerate or adhere to one year of DAPT, polymer-free bare metal stents remained the preferred device: the risk of restenosis was calculated to be less than the risk of major bleeding.

Enter a New Generation of Stents
The next few years saw a spectrum of attempted solutions to this complex issue with mixed results: bioresorbable scaffolds which would completely disappear after a few years, thinner strut stents with more biocompatible polymers, stents with bioresorbable polymers that in effect became bare metal stents after a few months, and finally, stents that were designed to hold a drug coating without a polymer.

The BioFreedom stent, manufactured by Biosensors, was of this latter type: a polymer and carrier-free stent that was coated with the proprietary limus drug, Biolimus A9. To test whether this novel drug-coated stent (DCS) could have similar results to BMS for HBR patients with only one month of DAPT, the LEADERS FREE study was launched. The results, published in 2015, were a big win for the DCS: at 390 days, the BioFreedom stent cut the incidence of target lesion revascularization (TLR) seen in bare metal stents by half and actually showed a decrease in stent thrombosis: a win on both measures. The take-away from this trial for many interventional cardiologists was that bare metal stents no longer had a role in the treatment of coronary narrowing. Adding in additional data for the LEADERS FREE II study resulted in the BioFreedom finally gaining FDA approval in April.

Results from Onyx ONE: a Head-to-Head Trial of the BioFreedom DCS vs. the Resolute Onyx DES
Refining the original concept of a polymer-based drug-eluting stent, new devices also had been developed with thinner-struts and more biocompatible polymers. One of these was the Resolute Onyx stent, manufactured by Medtronic. The question was: could a new generation polymer-based DES compete with the BioFreedom which had no polymer? To answer this, the Onyx ONE study was launched, . And the two-year results were just published.

After two-years, this study of 2,000 high-bleeding risk patients at 89 centers who were randomly assigned to the BioFreedom DCS or the Onyx DES and then given only one month of DAPT, followed by a year of single antiplatelet therapy (SAPT), showed virtually no difference in the results. The primary safety endpoint (composite of cardiac death, MI, or definite or probable ST) occurred in 208 (21.2%) patients in the ZES group and 199 (20.7%) patients in the DCS group at 2 years without significant differences in individual components of the composite endpoint. The secondary effectiveness endpoint (target lesion failure) occurred in 217 (22.1%) patients in the ZES group and 202 (21.0%) patients in the DCS group. The conclusions of the study:

Among patients at HBR treated with 1-month DAPT followed by SAPT, the Resolute Onyx polymer-based ZES had similar 2-year outcomes for the primary safety and secondary effectiveness endpoint compared with the BioFreedom polymer-free DCS.

As the editorial accompanying the study in JACC: Interventions stated in its title, "Less Is Not Always More," meaning that, while it might seem logical that removing a potentially troublesome component like the polymer would result in improved outcomes, that did not turn out to be the case. A similar intuitive mindset opined that bioresorbable stents which completely disappeared would prove superior when, in fact, the outcome turned out to be the opposite: all the more reason that well-conducted randomized controlled trials are necessary to determine safety and effectiveness of a device.

Reported by Burt Cohen, June 9, 2022