Abstract 16587: Edoxaban Associated With Fewer Serious Adverse Events and Lower Mortality Than Warfarin, Regardless of Burden of Comorbidities: Insights From the ENGAGE AF-TIMI 48 Trial
Background: Atrial fibrillation (AF) is more frequent in elderly pts and those with underlying cardiac and other comorbidities. The multicenter ENGAGE AF-TIMI 48 trial compared efficacy and safety of edoxaban vs warfarin in 21105 pts with AF over a mean follow up of 2.8 yrs. We hypothesized that despite more adverse events in pts with mod-high comorbidity, the benefits of edoxaban over warfarin would be similar to that seen in pts with less comorbidity.
Methods: Pts were classified using the Charlson Comorbidity Index (CCI) as low comorbidity (CCI <4, n=15860 pts) or mod-high comorbidity (CCI ≥4, n=5245 pts). Outcomes included study drug discontinuation, serious (non-bleeding) adverse events (SAEs), hepatic events, new neoplasms, and all cause death.
Results: Pts with CCI <4 were more likely male, with higher BMI, enrolled in NA, and received fewer cardiac co-medications. They had higher CHA2DS2VASc (mean 5.2 vs 4.0) and HASBLED (2.7 vs 2.4) scores, and higher median TTR with warfarin (69 vs 67%), P≤0.001 for each. Pts with CCI ≥4 had higher rates of drug discontinuation (40 vs 32%), serious adverse events (47 vs 34%), and all cause deaths (6.1 vs 3.4%), P<0.001 for each. Pts with CCI ≥4 randomized to warfarin were more likely to have SAEs and drug-related SAEs (both P<0.025) as compared to pts randomized to edoxaban. Edoxaban tended to reduce mortality to a similar degree (by 8-13%) compared to well-managed warfarin, regardless of CCI (Figure). Rates of hepatic events and neoplasms did not differ by CCI group or treatment arm.
Conclusions: Pts with AF have a high incidence of comorbidities (25% were classified as having moderate or high), which is associated to a higher rates of severe adverse events and death. Edoxaban was associated with fewer SAEs and death regardless of comorbidity score compared to well-managed warfarin.
Author Disclosures: R. Corbalan: None. C. Ruff: Research Grant; Significant; Daiichi-Sankyo. Honoraria; Modest; Daiichi-Sankyo, Bayer, Portola, Boehringer Ingelheim. T. Duris: Research Grant; Modest; Daiichi Sankyo. S. Juul-Möller: Research Grant; Modest; Daiichi Sankyo. J. Voitk: Research Grant; Modest; Daiichi Sankyo. M. Trevisan: Research Grant; Significant; Daiichi Sankyo. E. Antman: Research Grant; Significant; Daiichi Sankyo. E. Braunwald: Research Grant; Modest; AstraZeneca, Merck & Co, GSK, Bristol-Myers Squibb, Beckman Coulter, Roche Diagnostics, Pfizer, Sanofi, Johnson & Johnson. Research Grant; Significant; Daiichi Sankyo. Speakers Bureau; Modest; Uncompensated lectures for Merck and CVRx. Consultant/Advisory Board; Modest; Merck (unpaid consultant). Other; Modest; Lecture fees from Eli Lilly, Menarini, Medscape, and Bayer HealthCare. Consulting fees from Sanofi, Genzyme, Amorcyte, the Medicines Company, and Cardiorentis. R. Giugliano: Research Grant; Modest; Amgen. Research Grant; Significant; Amgen, Merck. Consultant/Advisory Board; Modest; American College of Cardiology, Bristol Myers Squibb, CVS Caremark, Pfizer. Consultant/Advisory Board; Significant; Amgen, Daiichi-Sankyo, Merck. Other; Modest; EC Member for FOURIER and EBBINGHAUS studies.
- © 2016 by American Heart Association, Inc.