Results of the Onyx One Clear study, evaluating the safety and effectiveness of one-month dual antiplatelet therapy followed by single antiplatelet therapy in high bleeding risk (HBR) patients undergoing percutaneous coronary intervention (PCI) using the Resolute Onyx (Medtronic) drug-eluting stent have been published online this week in Circulation: Cardiovascular Interventions. Findings of the study were initially shared virtually at the American College of Cardiology/World Congress of Cardiology’s virtual scientific sessions (ACC.20/WCC Virtual) in March.
The prospective, multicentre, non-randomised study was designed to complement the Onyx One Global Study and involved a primary analysis of cardiac death or myocardial infarction (MI) between one month and one year in over 1,500 patients pooled from the Onyx One US/Japan study and Onyx One randomised controlled trial. In the study, one-month clear was defined as DAPT adherence and without major adverse events during the first month following PCI.
The study’s findings showed that among high bleeding risk patients who were event free before DAPT discontinuation at one month, favourable safety and effectiveness through to one year support treatment with Resolute Onyx drug-eluting stents as part of an individualised strategy for shortened DAPT duration following.
The analysis included analysis of 1,506 patients who fulfilled the one-month clear criteria. Among this patient cohort, the mean HBR characteristic per patient was 1.6 with 44.7% having multiple risks. By two months and one year, respectively, 96.9% and 89.3% of patients were taking single antiplatelet therapy. Between one month and one year, the rate of the primary endpoint was 7%.
Resolute Onyx was recently approved for one-month DAPT labelling with an expended indication for HBR patients by the US Food and Drug Administration (FDA) based upon the findings of the Onyx One Clear study, as well as Onyx One Global. The drug-eluting stent received CE-mark approval for the one-month DAPT indication in June.
Following the FDA approval for the one-month DAPT labelling for Resolute Onyx, Cardiovascular News spoke to Onyx One Clear investigator Ajay Kirtane, professor of medicine at Columbia University Irving Medical Center (New York, USA), to discuss the significance of the development. A summary of the discussion can be found below.
Why are post-PCI bleeding avoidance strategies important?
Bleeding is bad for patients. Beyond the inconveniences that patients experience, it has been independently associated with increased rates of adverse events, including mortality.
What factors should determine when a patient is at high risk for bleeding events?
There are a number of criteria that have been associated with high bleeding risk. Age, the use of other blood thinners, kidney issues, and prior bleeding are just some of the common ones.
How common are these HBR patients in PCI procedures?
Estimates range from 20‒30% of PCI procedures, but with variability based upon patient and hospital characteristics.
What are the challenges in balancing the risk of bleeding versus the risk of ischaemic events?
Clinicians know that DAPT can reduce the rates of ischaemic events, but incurs a risk of bleeding. The recognition that optimal durations of DAPT therapy following DES implantation may vary based upon the bleeding risk of the patient is something that clinicians have struggled with since early DAPT guidance came out. Clinicians have been using DES in high-bleeding risk patients for a long time, but without clear FDA guidance on it.
How will the new labelling for the Resolute Onyx DES change approaches to PCI?
I started my career in interventional cardiology learning about the issue of late stent thrombosis. I remember when the FDA convened a panel that concluded that DAPT duration ought to be extended to 12 months—or more—in order to prevent stent thrombosis. At the time, this was based upon observational data and a fear that late stent thrombosis could harm many patients. What many clinicians recognised though was that extension of DAPT could also have its own harms—namely increased bleeding risk. So there was a trade-off in a sense. In the interim, newer stent designs have lowered the overall rates of stent thrombosis, and due to clinical studies like the Onyx One programme that studied these devices, we now recognise that for patients with high bleeding risk in whom shorter DAPT durations would be potentially preferred, this can indeed be an option. So for me it’s very fulfilling to see the evolution of the field over time. This is not to say that shorter (or longer) durations of DAPT are preferred for all, but rather that our newer devices afford us the flexibility as clinicians to make that choice thoughtfully.