André M Nicolau1, Ramon Corbalan2, Jose C Nicolau3, Christian T Ruff4, Wolfgang Zierhut5, Michael Kerschnitzki5, Tibor Duris6, Steen Juul-Möller7, Juri Voitk8, Marco Trevisan9, Francesco Nordio4, Elliott M Antman4, Robert P Giugliano4. 1. Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Botucatu, 720 São Paulo, Brazil. 2. Hospital Clinico Pontificia Universidad Catolica de Chile, Facultad de Medicina, Santiago, Chile. 3. Departamento de Cardiopneumologia, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, Brazil. 4. TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Hale Building, Room 7022, 60 Fenwood Road, Boston, MA 02115, USA. 5. Daiichi Sankyo Europe GmbH, Medical Affairs Antithrombotic & Cardiovascular Therapeutic Area, Zielstattstraße 48, 81379 Munich, Germany. 6. Fakultná nemocnica s poliklinikou, Nové Zámky, Slovakia. 7. Skåne University Hospital (SUS), Malmö, Sweden. 8. Department of Invasive Cardiology, Center of Cardiology, North Estonia Medical Center Foundation, J. Sütiste tee 19, 13419 Tallinn, Estonia. 9. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Abstract
AIMS: Non-vitamin K antagonist oral anticoagulants represent a new option for prevention of embolic events in patients with atrial fibrillation (AF). However, little is known about the impact of non-cardiac comorbidities on the efficacy and safety profile of these drugs. METHODS AND RESULTS: In a post hoc analysis of the ENGAGE AF-TIMI 48 trial, we analysed 21 105 patients with AF followed for an average of 2.8 years and randomized to either a higher-dose edoxaban regimen (HDER), a lower-dose edoxaban regimen, or warfarin. We used the updated Charlson Comorbidity Index (CCI) to stratify the patients according to the burden of concomitant disease (CCI = 0, 1, 2, 3, and ≥4). The treatment groups were then compared for safety, efficacy, and net clinical outcomes across CCI categories. There were 32.0%, 7.3%, 42.1%, 12.7%, and 6.0% of patients with CCI scores of 0, 1, 2, 3, and ≥4, respectively. A CCI score ≥4 was associated with significantly higher rates of thromboembolic events, bleeding, and death compared to CCI = 0 (P < 0.05 for each). The annualized rates of the primary net clinical outcome (stroke/systemic embolism, major bleeding, or death) for CCI = 0, 1, 2, 3, or ≥4 were 5.9%, 8.7%, 6.6%, 10.3%, and 13.6% (Ptrend < 0.001). There were no significant interactions between treatment with HDER vs. warfarin and efficacy, safety, and net outcomes across the CCI groups (P-interaction > 0.10 for each). CONCLUSION: Although increasing CCI scores are associated with worse outcomes, the efficacy, safety, and net clinical outcomes of edoxaban vs. warfarin were independent of the degree of comorbidity present. Published on behalf of the European Society of Cardiology. All rights reserved.
RCT Entities:
AIMS: Non-vitamin K antagonist oral anticoagulants represent a new option for prevention of embolic events in patients with atrial fibrillation (AF). However, little is known about the impact of non-cardiac comorbidities on the efficacy and safety profile of these drugs. METHODS AND RESULTS: In a post hoc analysis of the ENGAGE AF-TIMI 48 trial, we analysed 21 105 patients with AF followed for an average of 2.8 years and randomized to either a higher-dose edoxaban regimen (HDER), a lower-dose edoxaban regimen, or warfarin. We used the updated Charlson Comorbidity Index (CCI) to stratify the patients according to the burden of concomitant disease (CCI = 0, 1, 2, 3, and ≥4). The treatment groups were then compared for safety, efficacy, and net clinical outcomes across CCI categories. There were 32.0%, 7.3%, 42.1%, 12.7%, and 6.0% of patients with CCI scores of 0, 1, 2, 3, and ≥4, respectively. A CCI score ≥4 was associated with significantly higher rates of thromboembolic events, bleeding, and death compared to CCI = 0 (P < 0.05 for each). The annualized rates of the primary net clinical outcome (stroke/systemic embolism, major bleeding, or death) for CCI = 0, 1, 2, 3, or ≥4 were 5.9%, 8.7%, 6.6%, 10.3%, and 13.6% (Ptrend < 0.001). There were no significant interactions between treatment with HDER vs. warfarin and efficacy, safety, and net outcomes across the CCI groups (P-interaction > 0.10 for each). CONCLUSION: Although increasing CCI scores are associated with worse outcomes, the efficacy, safety, and net clinical outcomes of edoxaban vs. warfarin were independent of the degree of comorbidity present. Published on behalf of the European Society of Cardiology. All rights reserved.