A Randomized Controlled Trial with Resolute Onyx in One Month DAPT for High-Bleeding Risk Patients - Onyx ONE

Jun 29, 2022
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Medtronic
Date Presented:
09/26/2019
Date Published:
06/06/2022
Date Updated:
06/29/2022
Original Posted Date:
09/26/2019
References

Contribution To Literature:

Highlighted text has been updated as of June 29, 2022.

The Onyx ONE trial showed that Resolute Onyx DES implantation is noninferior to BioFreedom DCS, both with 1-month DAPT among patients undergoing PCI and with high bleeding risk.

Description:

The goal of the trial was to compare the safety and efficacy of 1 month of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) with either the Resolute Onyx drug-eluting stent (DES) or with the BioFreedom drug-coated stent (DCS) among patients at high bleeding risk.

Study Design

Eligible patients were randomized in a 1:1 fashion to either Resolute Onyx DES (durable polymer DES) (n = 1,003) or BioFreedom DCS (polymer-free) (n = 993). Patients received DAPT for 1 month. After 1 month, patients were given a prescription for single antiplatelet therapy (either aspirin or a P2Y12 inhibitor) at the discretion of the physician.

  • Total number of enrollees: 1,996
  • Duration of follow-up: 1 year
  • Mean patient age: 74 years
  • Percentage female: 33%

Inclusion criteria:

  • Adjunctive oral anticoagulation treatment planned to continue after PCI
  • Age ≥75 years old
  • Baseline hemoglobin <11 g/dl (or anemia requiring transfusion during the 4 weeks prior to randomization)
  • Any prior documented intracerebral bleed
  • Any documented stroke in the last 12 months
  • Hospital admission for bleeding during the prior 12 months
  • Nonskin cancer diagnosed or treated ≤3 years
  • Planned daily NSAID (other than aspirin) or steroids for ≥30 days after PCI
  • Planned surgery that would require interruption of DAPT (within the next 12 months)
  • Renal failure defined as: creatinine clearance <40 ml/min
  •  Thrombocytopenia (platelet count <100,000/mm3)
  •  Severe chronic liver disease defined as: subjects who have developed any of the following: variceal hemorrhage, ascites, hepatic encephalopathy, or jaundice
  • Expected noncompliance to prolonged DAPT for other medical reasons

Exclusion criteria:

  • Subjects requiring a planned PCI procedure after 1 month of index procedure
  • Procedure planned to require nonstudy stents, stand-alone plain old balloon angioplasty, or stand-alone atherectomy
  • Active bleeding at the time of inclusion
  • Cardiogenic shock
  • Subject with planned surgery or procedure necessitating discontinuation of DAPT within 1 month following index procedure
  • Subject not expected to comply with long-term single antiplatelet therapy
  • A known hypersensitivity or contraindication to aspirin, heparin and bivalirudin, P2Y12 inhibitors, mTOR-inhibiting drugs such as zotarolimus, Biolimus A9 (or its derivatives), cobalt, nickel, platinum, iridium, chromium, molybdenum, polymer coatings (e.g., BioLinx), stainless steel (or other metal ions found in 316 L stainless steel), zinc, or a sensitivity to contrast media, which cannot be adequately premedicated
  • PCI during the previous 6 months for a lesion other than the target lesion of the index procedure
  • Participation in another clinical study within 12 months after index procedure
  • Subjects with life expectancy of <2 years

Other salient features/characteristics:

  • Acute coronary syndrome: 51%
  • Atrial fibrillation: 32%
  • Mean high bleeding risk criteria: 1.6; 42% met ≥2 criteria
  • Single antiplatelet therapy use at 2 months: 94%; at 12 months: 93%

Principal Findings:

The primary safety outcome of cardiac death/myocardial infarction/stent thrombosis for Resolute vs. BioFreedom was 17.1% vs. 16.9% (p for noninferiority = 0.011, p for superiority = 0.84).

  • Cardiac death: 4.5% vs. 3.7%
  • Myocardial infarction: 13.4% vs. 14.7%
  • Stent thrombosis: 1.3% vs. 2.1%

Secondary outcomes for Resolute vs. BioFreedom:

  • Bleeding Academic Research Consortium (BARC) 2-5 bleeding: 15.1% vs. 13.7% (p = 0.4)
  • Stroke: 2.2% vs. 2.3%
  • Clinically driven target lesion revascularization: 2.8% vs. 4.0%

Two-year outcomes: The primary safety endpoint of cardiac death/myocardial infarction/stent thrombosis for Resolute vs. BioFreedom was 21.2% vs. 20.7% (p = 0.78).

  • All-cause death: 15.6% vs. 12.1% (p = 0.03)
  • Cardiac death: 7.4% vs. 5.8% (p = 0.17)
  • Target lesion failure: 22.1% vs. 21.0% (p = 0.54)
  • Definite or probable stent thrombosis: 1.6% vs. 2.5% (p = 0.20)
  • BARC 2-5 bleeding: 20.1% vs. 18.4% (p = 0.36)

Interpretation:

The results of this trial indicate that Resolute Onyx DES implantation is noninferior to BioFreedom DCS at 1 year, both with 1-month DAPT, among patients undergoing PCI and with high bleeding risk. Results were maintained out to 2 years. Though mortality was higher, there was no significant increase in stent thrombosis or bleeding to explain this and it did not persist after multivariable adjustment. Ischemic and bleeding rates were very high in both arms, which may be a reflection of the high-risk population studied.

It would be helpful to have a head-to-head comparison of routine DES PCI and 3- to 6-month DAPT duration vs. 1-month DAPT, as studied in this trial, since the event rates have been higher with BioFreedom DCS compared with contemporary DES in other trials (for instance, SORT OUT IX). Also, there appears to be emerging evidence for P2Y12 inhibitor monotherapy after a short duration of DAPT following PCI.

References:

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;15:1153-63.

Editorial Comment: Baber U. Polymer-Based Versus Polymer-Free Stents in High Bleeding Risk Patients: Less Is Not Always More. JACC Cardiovasc Interv 2022;15:1164-6.

Windecker S, Latib A, Kedhi E, et al., on behalf of the ONYX ONE Investigators. Polymer-based or Polymer-free Stents in Patients at High Bleeding Risk. N Engl J Med 2020;382:1208-18.

Presented by Dr. Stephan Windecker at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2019), San Francisco, CA, September 26, 2019.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Invasive Cardiovascular Angiography and Intervention, Anticoagulation Management and ACS, Interventions and ACS

Keywords: Acute Coronary Syndrome, Anticoagulants, Drug-Eluting Stents, Hemorrhage, Intracranial Hemorrhages, Myocardial Infarction, Neoplasms, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, Renal Insufficiency, Stroke, Thrombosis, Transcatheter Cardiovascular Therapeutics, TCT19


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