Thomas Vanassche1, Peter Verhamme2, Philip S Wells3, Annelise Segers4, Walter Ageno5, Marjolein P A Brekelmans6, Cathy Z Chen7, Alexander T Cohen8, Michael A Grosso9, Andria P Medina10, Michele F Mercuri9, Shannon M Winters7, George Zhang9, Jeffrey I Weitz11, Gary E Raskob12, Harry R Büller6. 1. University Hospitals Leuven, Dept. of Cardiovascular Sciences, Leuven, Belgium. Electronic address: thomas.vanassche@uzleuven.be. 2. University Hospitals Leuven, Dept. of Cardiovascular Sciences, Leuven, Belgium. 3. University of Ottawa, Ottawa Hospital Research Institute, Department of Medicine, Ottawa, Ontario, Canada. 4. Itreas BV, Amsterdam, The Netherlands. 5. University of Insubria, Department of Clinical and Experimental Medicine, Varese, Italy. 6. Academic Medical Center, Department of Vascular Medicine, Amsterdam, The Netherlands. 7. Daiichi Sankyo Inc., Basking Ridge, NJ, United States. 8. Guy's and St Thomas' Hospitals, King's College, Department of Haematological Medicine, London, United Kingdom. 9. Daiichi Sankyo Pharma Development, Basking Ridge, NJ, United States. 10. University of Oklahoma Health Science Center, College of Medicine, Oklahoma City, OK, United States. 11. Thrombosis & Atherosclerosis Research Institute and McMaster University, Hamilton, Canada. 12. University of Oklahoma Health Science Center, College of Public Health, Oklahoma City, OK, United States.
Abstract
BACKGROUND: Many patients with venous thromboembolism (VTE) are elderly, have multiple comorbidities and take several concomitant medications. Physicians may prefer warfarin over direct oral anticoagulants (DOACs) in such patients because comparative data are lacking. This analysis was designed to determine the effects of advanced age, comorbidities, and polypharmacy on the efficacy and safety of edoxaban and warfarin in patients with VTE. METHODS: Using data from the Hokusai-VTE study, we report rates of recurrent VTE and of clinically relevant bleeding by age category (<65, 65-75, and ≥75; <80 versus ≥80years), and by number of comorbidities (0, 1-2, >2) and concomitant medications (<3, 3-5, >5). Hazard ratios (HR) and corresponding 95% confidence intervals (CI) for edoxaban versus warfarin were determined and Kaplan-Meier methodology was used to construct time-to-event curves. At 3months, pre- and postdose levels of edoxaban were measured using mass spectrometry. For warfarin-treated patients, the time in therapeutic range was calculated. The study was approved by institutional review boards; informed consent was obtained. RESULTS:Recurrent VTE increased with advanced age, multiple comorbidities, and polypharmacy in warfarin-treated patients but not with edoxaban. Edoxaban was more effective than warfarin in patients ≥75years of age and in those with multiple comorbidities. In the 517 patients over 80years of age, recurrent VTE occurred in 2.8% given edoxaban and in 5.7% given warfarin (HR 0.51, 95% CI 0.21-1.24). Bleeding increased with age, comorbidity, and polypharmacy regardless of treatment, but the relative safety of edoxaban versus well-managed warfarin was maintained. Age, comorbidity, and polypharmacy did not impact edoxaban concentrations. CONCLUSIONS: These data suggest that a once-daily fixed dose of edoxaban is more effective and at least as safe as warfarin in high-risk VTE patients identified by older age, more comorbidities, and polypharmacy. CLINICAL TRIAL REGISTRATION: NCT00986154.
RCT Entities:
BACKGROUND: Many patients with venous thromboembolism (VTE) are elderly, have multiple comorbidities and take several concomitant medications. Physicians may prefer warfarin over direct oral anticoagulants (DOACs) in such patients because comparative data are lacking. This analysis was designed to determine the effects of advanced age, comorbidities, and polypharmacy on the efficacy and safety of edoxaban and warfarin in patients with VTE. METHODS: Using data from the Hokusai-VTE study, we report rates of recurrent VTE and of clinically relevant bleeding by age category (<65, 65-75, and ≥75; <80 versus ≥80years), and by number of comorbidities (0, 1-2, >2) and concomitant medications (<3, 3-5, >5). Hazard ratios (HR) and corresponding 95% confidence intervals (CI) for edoxaban versus warfarin were determined and Kaplan-Meier methodology was used to construct time-to-event curves. At 3months, pre- and postdose levels of edoxaban were measured using mass spectrometry. For warfarin-treated patients, the time in therapeutic range was calculated. The study was approved by institutional review boards; informed consent was obtained. RESULTS: Recurrent VTE increased with advanced age, multiple comorbidities, and polypharmacy in warfarin-treated patients but not with edoxaban. Edoxaban was more effective than warfarin in patients ≥75years of age and in those with multiple comorbidities. In the 517 patients over 80years of age, recurrent VTE occurred in 2.8% given edoxaban and in 5.7% given warfarin (HR 0.51, 95% CI 0.21-1.24). Bleeding increased with age, comorbidity, and polypharmacy regardless of treatment, but the relative safety of edoxaban versus well-managed warfarin was maintained. Age, comorbidity, and polypharmacy did not impact edoxaban concentrations. CONCLUSIONS: These data suggest that a once-daily fixed dose of edoxaban is more effective and at least as safe as warfarin in high-risk VTEpatients identified by older age, more comorbidities, and polypharmacy. CLINICAL TRIAL REGISTRATION: NCT00986154.
Authors: Gabriello Marchetti; Emanuele Bertaglia; Alberto Camerini; Giuseppe De Angelis; Lucia Filippucci; Antonio Maggi; Sebastiano Marra; Carlo Racani; Carlo Serrati Journal: J Atr Fibrillation Date: 2020-02-28
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