Mariusz Tomaniak1,2, Ply Chichareon3,4, Dominika Klimczak-Tomaniak5, Kuniaki Takahashi3, Norihiro Kogame3, Rodrigo Modolo3,6, Rutao Wang7,8, Masafumi Ono3, Hironori Hara3, Chao Gao7,8, Hideyuki Kawashima3, Tessa Rademaker-Havinga9, Scot Garg10, Nick Curzen11, Michael Haude12, Janusz Kochman2, Tommaso Gori13, Gilles Montalescot14, Dominick J Angiolillo15, Davide Capodanno16, Robert F Storey17, Christian Hamm18, Pascal Vranckx19, Marco Valgimigli20, Stephan Windecker20, Yoshinobu Onuma21, Patrick W Serruys22,23, Richard Anderson24. 1. Department of Cardiology, Erasmus University Medical Centre, Erasmus University, Rotterdam, The Netherlands. 2. First Department of Cardiology, Medical University of Warsaw, Warsaw, Poland. 3. Department of Cardiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. 4. Division of Cardiology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand. 5. Department of Immunology, Transplantation and Internal Medicine, Department of Cardiology, Hypertension and Internal Medicine, Medical University of Warsaw, Warsaw, Poland. 6. Department of Internal Medicine, Cardiology Division, University of Campinas (UNICAMP), Campinas, Brazil. 7. Department of Cardiology, Xijing Hospital, Xi'an, China. 8. Department of Cardiology, Radboud University, Nijmegen, The Netherlands. 9. Cardialysis Core Laboratories and Clinical Trial Management, Rotterdam, The Netherlands. 10. Royal Blackburn Hospital, Blackburn, UK. 11. University Hospital Southampton NHSF, Southampton, UK. 12. Department of Cardiology, Städtische Kliniken Neuss, Neuss, Germany. 13. Deutsches Zentrum für Herz und Kreislauf Forschung, Standort Rhein-Main, University Medical Center Mainz, Mainz, Germany. 14. Cardiology Department, ACTION Study Group, Nîmes University Hospital, Montpellier University, Nîmes, France. 15. Division of Cardiology, University of Florida College of Medicine, Jacksonville, FL, USA. 16. Division of Cardiology, A.O.U. "Policlinico-Vittorio Emanuele", University of Catania, Catania, Italy. 17. Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Cardiology and Cardiothoracic Surgery Directorate, Sheffield Teaching Hospitals NHS Foundation Trust, Cardiovascular Research Unit, Centre for Biomedical Research, Northern General Hospital, Sheffield, UK. 18. University of Giessen, Giessen, Germany. 19. Department of Cardiology and Critical Care Medicine, Hartcentrum Hasselt, Jessa Ziekenhuis, Hasselt, Belgium. 20. Department of Cardiology, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland. 21. Department of Cardiology, National University of Ireland, Galway (NUIG), University Road, Galway, H91 TK33, Ireland. 22. NHLI, Imperial College London, London, UK. patrick.w.j.c.serruys@gmail.com. 23. Department of Cardiology, National University of Ireland, Galway (NUIG), University Road, Galway, H91 TK33, Ireland. patrick.w.j.c.serruys@gmail.com. 24. University Hospital of Wales, Cardiff, UK.
Abstract
BACKGROUND:Impaired renal function (IRF) is associated with increased risks of both ischemic and bleeding events. Ticagrelor has been shown to provide greater absolute reduction in ischemic risk following acute coronary syndrome (ACS) in those with versus without IRF. METHODS: A pre-specified sub-analysis of the randomized GLOBAL LEADERS trial (n = 15,991) comparing the experimental strategy of 23-month ticagrelor monotherapy (after 1-month ticagrelor and aspirin dual anti-platelet therapy [DAPT]) with 12-month DAPT followed by 12-month aspirinafter percutaneous coronary intervention (PCI) in ACS and stable coronary artery disease (CAD) patients stratified according to IRF (glomerular filtration rate < 60 ml/min/1.73 m2). RESULTS: At 2 years, patients with IRF (n = 2171) had a higher rate of the primary endpoint (all-cause mortality or centrally adjudicated, new Q-wave myocardial infarction [MI](hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.35-1.98, padj = 0.001), all-cause death, site-reported MI, all revascularization and BARC 3 or 5 type bleeding, compared with patients without IRF. Among patients with IRF, there were similar rates of the primary endpoint (HR 0.82, 95% CI 0.61-1.11, p = 0.192, pint = 0.680) and BARC 3 or 5 type bleeding (HR 1.10, 95% CI 0.71-1.71, p = 0.656, pint = 0.506) in the experimental versus the reference group. No significant interactions were seen between IRF and treatment effect for any of the secondary outcome variables. Among ACS patients with IRF, there were no between-group differences in the rates of the primary endpoint or BARC 3 or 5 type bleeding; however, the rates of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, MI, or revascularization (pint = 0.028) and net adverse clinical events (POCE and BARC 3 or 5 type bleeding) (pint = 0.045), were lower in the experimental versus the reference group. No treatment effects were found in stable CAD patients categorized according to presence of IRF. CONCLUSIONS: IRF negatively impacted long-term prognosis after PCI. There were no differential treatment effects found with regard to all-cause death or new Q-wave MI after PCI in patients with IRF treated with ticagrelor monotherapy. CLINICAL TRIAL REGISTRATION: The trial has been registered with ClinicalTrials.gov, number NCT01813435.
RCT Entities:
BACKGROUND: Impaired renal function (IRF) is associated with increased risks of both ischemic and bleeding events. Ticagrelor has been shown to provide greater absolute reduction in ischemic risk following acute coronary syndrome (ACS) in those with versus without IRF. METHODS: A pre-specified sub-analysis of the randomized GLOBAL LEADERS trial (n = 15,991) comparing the experimental strategy of 23-month ticagrelor monotherapy (after 1-month ticagrelor and aspirin dual anti-platelet therapy [DAPT]) with 12-month DAPT followed by 12-month aspirin after percutaneous coronary intervention (PCI) in ACS and stable coronary artery disease (CAD) patients stratified according to IRF (glomerular filtration rate < 60 ml/min/1.73 m2). RESULTS: At 2 years, patients with IRF (n = 2171) had a higher rate of the primary endpoint (all-cause mortality or centrally adjudicated, new Q-wave myocardial infarction [MI](hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.35-1.98, padj = 0.001), all-cause death, site-reported MI, all revascularization and BARC 3 or 5 type bleeding, compared with patients without IRF. Among patients with IRF, there were similar rates of the primary endpoint (HR 0.82, 95% CI 0.61-1.11, p = 0.192, pint = 0.680) and BARC 3 or 5 type bleeding (HR 1.10, 95% CI 0.71-1.71, p = 0.656, pint = 0.506) in the experimental versus the reference group. No significant interactions were seen between IRF and treatment effect for any of the secondary outcome variables. Among ACS patients with IRF, there were no between-group differences in the rates of the primary endpoint or BARC 3 or 5 type bleeding; however, the rates of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, MI, or revascularization (pint = 0.028) and net adverse clinical events (POCE and BARC 3 or 5 type bleeding) (pint = 0.045), were lower in the experimental versus the reference group. No treatment effects were found in stable CADpatients categorized according to presence of IRF. CONCLUSIONS: IRF negatively impacted long-term prognosis after PCI. There were no differential treatment effects found with regard to all-cause death or new Q-wave MI after PCI in patients with IRF treated with ticagrelor monotherapy. CLINICAL TRIAL REGISTRATION: The trial has been registered with ClinicalTrials.gov, number NCT01813435.
Authors: Patrizia Natale; Suetonia C Palmer; Valeria M Saglimbene; Marinella Ruospo; Mona Razavian; Jonathan C Craig; Meg J Jardine; Angela C Webster; Giovanni Fm Strippoli Journal: Cochrane Database Syst Rev Date: 2022-02-28