Benjamin M Scirica1, Sameer Bansilal2, Farideh Davoudi3, Paul W Armstrong4, Robert M Clare5, Phillip J Schulte6, Karen S Pieper5, Richard C Becker7, Stefan K James8, Robert F Storey9, Philippe Gabriel Steg10, Claes Held8, Anders Himmelmann11, Kenneth W Mahaffey12, Lars Wallentin8, Christopher P Cannon13. 1. Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. 2. The Zena and Michael Weiner Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY. 3. Massachusetts General Hospital, Boston, MA. 4. Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada. 5. Duke Clinical Research Institute, Duke University Medical Center, Durham, NC. 6. Department of Health Sciences Research, Mayo Clinic, Rochester, MN; former employee at Duke Clinical Research Institute, Duke University Medical Center, Durham, NC. 7. Division of Cardiovascular Health and Disease, Heart, Lung and Vascular Institute, University of Cincinnati College of Medicine, Cincinnati, OH. 8. Department of Medical Sciences, Cardiology, and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. 9. Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom. 10. Department Hospitalo-Universitaire FIRE, AP-HP, Hopital Bichat, Paris, France; Paris Diderot University, Sorbonne Paris Cite, Paris, France, NHLI, Imperial College, ICMS, Royal Brompton Hospital, London, UK; FACT (French Alliance for Cardiovascular Trials), an F-CRIN network, INSERM U1148, Paris, France. 11. AstraZeneca Research and Development, Gothenburg, Sweden. 12. Stanford Center for Clinical Research (SCCR), Department of Medicine, Stanford University School of Medicine, Stanford, CA. 13. Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. Electronic address: cpcannon@bwh.harvard.edu.
Abstract
BACKGROUND: Although bradyarrhythmias have been observed with ticagrelor and its use with advanced atrioventricular block is not recommended, questions arise regarding its use in patients with mild conduction abnormalities. The objectives were to compare rates of clinically relevant arrhythmias in relation to any mild baseline conduction abnormality in patients with acute coronary syndrome randomized toticagrelor versus clopidogrel. METHODS: We included all subjects in the electrocardiographic (ECG) substudy of the Platelet Inhibition and Patient Outcomes trial, excluding those with missing baseline ECG or with a pacemaker at baseline (N = 15,460). Conduction abnormality was defined as sinus bradycardia, first-degree atrioventricular block, hemiblock, or bundle-branch block. The primary arrhythmic outcome was the composite of any symptomatic brady- or tachyarrhythmia, permanent pacemaker placement, or cardiac arrest through 12 months. RESULTS:Patients with baseline conduction abnormalities (n = 4,256, 27.5%) were older and more likely to experience the primary arrhythmic outcome. There were no differences by ticagrelor versus clopidogrel in the composite arrhythmic end point in those with baseline conduction disease (1-year cumulative incidence rate: 17% for both study arms; hazard ratio: 0.99 [0.86-1.15]) or without baseline conduction disease (1-year cumulative incidence rate: clopidogrel 12.8% vs ticagrelor 12.4%; hazard ratio: 0.98 (0.88-1.09). There were also no statistically significant differences between ticagrelor and clopidogrel in the rates of bradycardic (or any individual arrhythmic) events in patients with baseline conduction abnormalities. CONCLUSIONS:Ticagrelor compared to clopidogrel did not increase arrhythmic events even in subjects with acute coronary syndrome who present with mild conduction abnormalities on their baseline ECG.
RCT Entities:
BACKGROUND: Although bradyarrhythmias have been observed with ticagrelor and its use with advanced atrioventricular block is not recommended, questions arise regarding its use in patients with mild conduction abnormalities. The objectives were to compare rates of clinically relevant arrhythmias in relation to any mild baseline conduction abnormality in patients with acute coronary syndrome randomized to ticagrelor versus clopidogrel. METHODS: We included all subjects in the electrocardiographic (ECG) substudy of the Platelet Inhibition and Patient Outcomes trial, excluding those with missing baseline ECG or with a pacemaker at baseline (N = 15,460). Conduction abnormality was defined as sinus bradycardia, first-degree atrioventricular block, hemiblock, or bundle-branch block. The primary arrhythmic outcome was the composite of any symptomatic brady- or tachyarrhythmia, permanent pacemaker placement, or cardiac arrest through 12 months. RESULTS:Patients with baseline conduction abnormalities (n = 4,256, 27.5%) were older and more likely to experience the primary arrhythmic outcome. There were no differences by ticagrelor versus clopidogrel in the composite arrhythmic end point in those with baseline conduction disease (1-year cumulative incidence rate: 17% for both study arms; hazard ratio: 0.99 [0.86-1.15]) or without baseline conduction disease (1-year cumulative incidence rate: clopidogrel 12.8% vs ticagrelor 12.4%; hazard ratio: 0.98 (0.88-1.09). There were also no statistically significant differences between ticagrelor and clopidogrel in the rates of bradycardic (or any individual arrhythmic) events in patients with baseline conduction abnormalities. CONCLUSIONS:Ticagrelor compared to clopidogrel did not increase arrhythmic events even in subjects with acute coronary syndrome who present with mild conduction abnormalities on their baseline ECG.
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