One Month Dual Antiplatelet Therapy in High Bleeding Risk Patients: Primary Results of Onyx ONE Clear Ajay J. Kirtane, MD, SM Columbia University Irving Medical Center /New York-Presbyterian Hospital and the Cardiovascular Research Foundation, New York, NY, USA email : akirtane@columbia.edu twitter : @ajaykirtane and David E. Kandzari, Roxana Mehran, Matthew J. Price, Daniel Simon, Azeem Latib, Elvin Kedhi, Alexandre Abizaid, Stephen Worthley, Azfar Zaman, Lisa Bousquette, Lilian Lee, Te-Hsin Lung, Stephan Windecker and Gregg W. Stone on behalf of the Onyx ONE and Onyx ONE Clear Investigators
Disclosure Statement of Financial Interest Ajay J. Kirtane Institutional funding to Columbia University and/or Cardiovascular Research Foundation from: – Medtronic, Boston Scientific Corporation, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, ReCor Medical Personal: CME/conference honoraria and travel/meals only
Background Up to 40% of patients undergoing PCI have high bleeding risk (HBR) • characteristics Guidelines recommend 3-6 months of DAPT for HBR patients undergoing PCI with • consideration for DAPT duration as short as 1 month in selected patients Resolute Onyx ™ is a thin strutted, conformable stent with a biocompatible (Biolinx ™ ) • polymer and sustained drug elution over several months The Onyx ONE RCT demonstrated noninferior outcomes of Resolute Onyx • compared with a polymer-free drug-coated stent in a broad range of HBR patients receiving 1-month DAPT 1 Onyx ONE 1 Windecker S, et al. N Engl J Med . 2020. doi: 10.1056/NEJMoa1910021. [Epub ahead of print] Clear
Objective To evaluate the safety and efficacy of the Resolute Onyx stent among HBR patients undergoing PCI with planned 1-month DAPT 1. Extension of Onyx ONE RCT results 2. Patient enrollment from USA and Japan 3. Prospective, single arm trial design 4. Powered analysis to support indication approval Onyx ONE Clear
Rationale for Prospective Single Arm Design in US/Japan No approved DES with 1-month DAPT in conjunction with limited BMS use • precluding 1-month RCT designs like Onyx ONE RCT Extension of Onyx ONE RCT data to US and Japan with • – Similar inclusion / exclusion criteria – Similar case report forms – Same endpoint definitions – Same angiographic core laboratory – Same CEC adjudication processes Onyx ONE Clear
Study Design Prospective, Multicenter, Single-arm Study High Bleeding Risk patients undergoing PCI (no lesion, vessel limitations) Resolute Onyx ™ ZES Resolute Onyx ZES with 1 Month DAPT with 1 Month DAPT from Onyx ONE RCT (N=1000) US & Japan (N=700 + max 100) Clinical Follow-up 1mo 2mo 6mo 1yr 2yr Cardiac death/MI assessed in “1 - month clear” patients from 1 -12 Mo Primary endpoint: compared to a 9.7% performance goal from HBR short DAPT studies Secondary endpoints: Acute success rates, BARC bleeding, TVF, death, MI, stent thrombosis, stroke, revascularizations, MACE and TLF Antiplatelet Therapy: DAPT for 1 month, thereafter SAPT only “1 - month clear” is defined as patients who were adherent to DAPT within the 1 st month after PCI Onyx ONE and free of events that would preclude 1-month DAPT cessation Clear NCT03647475
HBR Inclusion Criteria (One or More) Elderly (age ≥75 years) Thrombocytopenia (<100,000/mm 3 ) OAC planned after PCI Cancer diagnosed or treated within 3 yrs Renal failure (CrCl <40 ml/min) Stroke within 1 year or any prior ICH Planned surgery <1 year Severe chronic liver disease Anemia (Hgb <11 g/dl) Long-term NSAID or steroid use Hospitalization for bleeding within 1 year Expected DAPT non-compliance Onyx ONE Clear
Antithrombotic Therapy PCI After PCI, DAPT was prescribed for 1-month, including: • – Daily dose of aspirin (75-100 mg) AND P 2 Y 12 – P 2 Y 12 inhibitor (clopidogrel preferred, others allowed) ASA • Patients receiving OAC could receive single or dual antiplatelet therapy during this 1 st month after PCI • After 1-month DAPT, single antiplatelet therapy was prescribed with 1M ASA / P 2 Y 12 either (at physician discretion): – Aspirin OR – P 2 Y 12 inhibitor Onyx ONE Clear
Sample Size Calculation Definition “1 - month clear” Primary Endpoint Cardiac death or MI Event-free 2 in 1 st month • Expected event rate 1 6.8% Adherent to DAPT for 1 st month • Performance goal 9.7% = Effective analysis population One-sided type I error ( α ) 0.025 Power >97% Effective sample size 1360 patients “1 - month clear” attrition rate 20% Total sample size 1700 enrolled patients (1000 Onyx ONE RCT and 700 from Onyx ONE Clear) Onyx ONE 1 Based on adjusted data from LEADERS-FREE, ZEUS and Senior short DAPT studies 2 Events that would preclude DAPT discontinuation at 1 month Clear
Trial Organization Principal Investigators D. Kandzari, A. Kirtane (Co-PIs) Executive Committee G. Stone (Program Chair), A. Abizaid, E. Kedhi, A. Latib, R. Mehran, M. Price, D. Simon, S. Windecker, S. Worthley, A. Zaman DSMB JP. Carrozza (Chair) Cardiovascular Research Foundation, New York NY, USA CEC S. Marx (Chair) Cardiovascular Research Foundation, New York NY, USA Angiographic Core Lab Cardiovascular Research Foundation, New York NY, USA Statistics Medtronic (Analysis) and Baim Institute for Clinical Research, Boston MA, USA (Independent Validation) Data Management & Medtronic, Santa Rosa CA, USA Monitoring Sponsor Medtronic, Santa Rosa CA, USA Onyx ONE Clear
Participating Centers United States Japan ▪ Texas: J Choi, S Potluri, T Tolleson, A Shah ▪ Fukuoka: K Ando ▪ New York: R Caputo, T Nazif, L Gruberg ▪ Kanagawa: S Saito, Y Ikari ▪ Alabama: M Kanitkar ▪ Tokyo: K Kozuma ▪ South Carolina: B McLaurin ▪ Kumamoto: T Sakamoto ▪ Ohio: T Smith, NH Kander, J Li, J Khatri ▪ Florida: D Spriggs, S Singh, M Tulli, T Noel ▪ Georgia: D Kandzari, H Liberman ▪ California: MJ Price, S Brar, A Loussararian, D Lee, W Lim ▪ Wisconsin: G Larrain, T Nfor ▪ Washington, DC: R Waksman ▪ Virginia: M Ragosta, M Arcarese, D Talreja ▪ Oregon: H Golwala ▪ Michigan: S Chetcuti ▪ Tennessee: J Webber, E Haddad ▪ Illinois: A Shroff ▪ Missouri: A Salisbury ▪ Minnesota: J Dutcher, J Chambers, W Ginete ▪ North Dakota: T Haldis ▪ New Jersey: K Sanghvi Onyx ONE RCT ▪ Massachusetts: D Pinto Onyx ONE US/Japan Onyx ONE Clear
Top Enrolling Sites Site PI Hospital Location Patients Choi, James Baylor Heart & Vascular Hospital 78 Dallas, TX Caputo, Ronald Saint Joseph's Hospital Health Center 71 Syracuse, NY Kanitkar, Mihir Huntsville Hospital 57 Huntsville, AL McLaurin, Brent AnMed Health Medical Center 54 Anderson, SC Potluri, Srinivasa The Heart Hospital Baylor Plano 48 Plano, TX Smith, Timothy The Christ Hospital 25 Cincinnati, OH Spriggs, Douglas Morton Plant Hospital 24 Clearwater, FL Tolleson, Thaddeus UT Health East Texas 24 Tyler, TX Kandzari, David Piedmont Atlanta Hospital 22 Atlanta, GA New York-Presbyterian Hospital/ Nazif, Tamim 20 New York, NY Columbia University Medical Center Price, Matthew J. Scripps Green Hospital 19 La Jolla, CA Gruberg, Luis Southside Hospital 19 Manhasset, NY Ando, Kenji Kokura Memorial Hospital 18 Kitakyushu, Fukuoka Larrain, German Aspirus Wausau Hospital 18 Wausau, WI Onyx ONE Clear
Patient Flowchart Onyx ONE RCT Onyx ONE US/Japan Resolute Onyx pts (N=1019) (N=752: US 713 + Japan 39) 1 Japanese patient not eligible yet for 1-yr 1 patient did not consent follow-up at time of database snapshot for data use outside of Onyx ONE RCT Onyx ONE As-Treated population (N=1769) 263 Not “1 - month Clear”: ▪ 116 Experienced event within 30 days ▪ 147 Not adherent to DAPT protocol Onyx ONE Clear (N=1506) Primary analysis population 9 Withdrawal 6 Visit not done 1-Year Follow-up Analysis n=1491 (99.0%) “1 - month clear” is defined as patients who were adherent to DAPT within the 1 st month after PCI Onyx ONE and free of events that would preclude 1-month DAPT cessation Clear
Baseline Characteristics Onyx ONE Onyx ONE Onyx ONE % or mean ± SD RCT 1 US/Japan 1 Clear (N=1506) (N=905) (N= 601) 74.0 ± 9.5 73.8 ± 9.6 74.2 ± 9.5 Age (yrs) Female 32.3 32.2 32.6 Diabetes 39.4 37.2 42.6 Hypertension 84.0 80.0 90.0 Hyperlipidemia 72.4 64.4 84.5 Previous MI 26.3 26.0 26.8 Previous revascularization 36.2 27.6 49.1 Atrial fibrillation 35.6 33.4 38.9 Silent ischemia 10.8 9.5 12.8 Chronic coronary syndrome 40.5 39.1 42.7 Acute coronary syndrome 48.6 51.4 44.5 STEMI 4.2 5.7 1.8 Non-STEMI 21.7 26.0 15.2 Unstable angina 22.8 19.7 27.5 Onyx ONE 1 Onyx patients meeting “1 - month clear” definition Clear
HBR Inclusion Criteria Elderly (age ≥75 yr) 59.0 OAC Mean 1.6 41.0 Anemia or transfusion 14.4 criteria / pt Renal failure 12.5 Active or recent cancer 7.4 Planned surgery 6.6 44% met ≥ 2 Expected DAPT non-compliance 4.2 HBR criteria Long-term NSAID or steroids 3.1 Hospital for bleeding 2.8 Stroke < 1yr 2.6 Prior ICH 1.7 Thrombocytopenia 1.7 Severe liver disease 0.9 0 10 20 Patients meeting criteria (%) 30 40 50 60 70 N = 1506 Onyx ONE Clear
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