A durable-polymer stent plus short-duration dual antiplatelet therapy (DAPT) was a safe and effective strategy in patients with high bleeding risk, researchers showed in the randomized ONYX ONE trial.
Polymer-based zotarolimus-eluting stent Resolute Onyx was non-inferior to the polymer-free umirolimus-coated BioFreedom in patients receiving just 1 month of DAPT due to high bleeding risk characteristics. Non-inferiority was confirmed both for:
- Safety, in terms of composite rate of death from cardiac causes, MI, and stent thrombosis at 1 year: 17.1% vs 16.9% (P=0.01 for non-inferiority)
- Efficacy, in terms of target lesion failure or combined death from cardiac causes, target vessel MI, or clinically-indicated target lesion revascularization at 1 year: 17.6% vs 17.4% (P=0.007 for noninferiority)
The findings were “noteworthy because more than 50% of the patients in our trial presented with acute coronary syndromes,” according to the ONYX ONE group led by Stephan Windecker, MD, of Bern University Hospital in Switzerland.
“The trial thus extends earlier results suggesting that bleeding, more than ischemic risk, should determine clinical decision making regarding the duration of DAPT,” study authors added in their manuscript published online in the New England Journal of Medicine. The main findings were previously reported at the Transcatheter Cardiovascular Therapeutics meeting in 2019.
Current guidelines recommend 3 to 6 months of DAPT in patients at high bleeding risk after PCI with drug-eluting stents.
Resolute Onyx, approved by the FDA in late 2018, appears to be a good option for patients at high bleeding risk who need an abbreviated DAPT regimen, concluded coauthor Roxana Mehran, MD, of Mount Sinai School of Medicine in New York City.
“It is important to note that these patients at high bleeding risk have high event rates and we need to continue to survey them closely in terms of risk reduction and close follow-up. I am not surprised by the findings as I think these events are not necessarily stent-related events, but rather related to the high risk profile of these patients,” Mehran said.
“Of note, the comparator stent [BioFreedom] is not FDA approved and is a thicker strutted stent. As such, the results are not surprising, although I would have hoped to see superiority of Onyx given the difference in strut thickness,” commented Sripal Bangalore, MD, MHA, of New York University School of Medicine in New York City, who was not involved in the study.
What might have been surprising was that rates of stent thrombosis were 1.3% and 2.1%, respectively — “higher than what we are used to,” Bangalore told MedPage Today. He cited the STOPDAPT-2 trial in which the durable-polymer Xience stent was associated with a 0.3% rate of stent thrombosis at 1 year in a high bleeding-risk population on 1 month of DAPT.
STOPDAPT-2 used intravascular ultrasound guidance for stent optimization and, after 1 month of DAPT, patients dropped aspirin and continued the P2Y12 inhibitor, Bangalore noted. “It therefore remains to be seen whether stent type, optimal deployment, or the antiplatelet type makes a difference in these findings.”
For ONYX ONE, Windecker’s group randomized 1,996 PCI patients with coronary artery disease who were at high bleeding risk. Mean age was 74 years, and women represented roughly one in three participants. Diabetes was noted in 38.6%.
All patients were candidates for 1-month DAPT, followed by single antiplatelet agent thereafter. Trial participants were more likely to keep aspirin than a P2Y12 inhibitor as their longer-term antiplatelet.
Bleeding Academic Research Consortium grade 2-5 bleeding occurred in 15.1% of Resolute Onyx recipients and 13.7% of the BioFreedom group.
ONYX ONE builds on the LEADERS FREE trial, which showed BioFreedom to be superior to a bare metal stent in patients with a similar proportion and distribution of high bleeding risk features, according to Windecker and colleagues.
“Event rates for the primary outcome were higher in this trial than in the LEADERS FREE trial, which was driven by a greater incidence of periprocedural MI in both groups. These higher rates may be due to differences in patient populations but are more likely to be due to differences in ascertainment and adjudication of events between the trials,” they said.
Heart attacks were adjudicated according to the Third Universal Definition of MI in ONYX ONE.
“The vast majority of diagnoses of periprocedural MI in the present trial were based on angiographic findings, without symptoms or electrocardiographic changes, in patients in whom both preprocedural and postprocedural troponin levels were measured,” the investigators noted.
One major limitation of ONYX ONE was that PCI operators were not blinded to stent type.
Crossover was more common when people were assigned to polymer-free drug-coated stents, “which may have contributed to the observed differences in device success,” Windecker’s team suggested.
The trial was also not powered to detect between-group differences in rarer outcomes such as stent thrombosis, and it lacked a control group of patients taking DAPT for 3 or 6 months.
“Therefore, it is unknown whether patients at high bleeding risk who were selected to undergo PCI would have a superior net clinical benefit with a course of DAPT longer than 1 month,” according to the authors.
The trial was funded by Medtronic.
Windecker reported receiving grants from Amgen, Abbott, Biotronik, Boston Scientific, Bayer, BMS, CSL Behring, Edwards Lifesciences, Medtronic, Polares, and Sinomed.