Dronedarone vs placebo in patients with atrial fibrillation or atrial flutter across a range of renal function: a post hoc analysis of the ATHENA trial

Abstract Background The use of antiarrhythmic drugs in patients with chronic kidney disease (CKD) is challenging due to issues with renal clearance, drug accumulation and increased proarrhythmic risks. Since CKD is a common comorbidity with atrial fibrillation (AF), it is important to establish the efficacy and safety for antiarrhythmic drug treatment in patients with CKD. Purpose To evaluate the efficacy and safety of dronedarone in patients with AF or atrial flutter (AFL) across different stages of renal impairment. Methods In this post-hoc analysis of ATHENA (NCT00174785), a randomised, double-blind trial of dronedarone 400 mg BID vs placebo in patients with AF or AFL plus additional risk factors for death and a calculated glomerular filtration rate ≥10 mL/min, the primary outcome was time to first cardiovascular (CV) hospitalisation or death. Renal function (estimated glomerular filtration rate [eGFR]) was assessed using CKD Epidemiology Collaboration equation and patients were grouped by eGFR (10–44, 45–59, ≥60 mL/min). Log-rank testing and Cox regression were used to compare time to events between treatment groups. Results In ATHENA, 43.6% of placebo and 42.2% of dronedarone patients had mild-to-moderate CKD (Table). Median time to CV hospitalisation/death was longer in all strata for dronedarone vs placebo, reaching significance in the 45–59 and ≥60 mL/min groups (Figure 1). There was a trend towards more treatment-emergent adverse events (TEAEs), deaths and discontinuations due to TEAEs in patients with eGFR 10–44 mL/min. No clear difference in safety was seen between treatment arms except for discontinuations, which were higher with dronedarone. Conclusions This analysis confirms the efficacy of dronedarone, demonstrated in ATHENA, across different stages of renal impairment. Further assessment of safety will require larger populations of patients with CKD. Table 1 eGFR 10–44 mL/min eGFR 45–59 mL/min eGFR ≥60 mL/min Placebo (n=322) Dronedarone (n=313) Placebo (n=683) Dronedarone (n=649) Placebo (n=1301) Dronedarone (n=1320) Age at BL, years, mean (SD) 76.7 (6.6) 77.1 (6.3) 74.5 (7.2) 73.6 (6.9) 69.0 (9.4) 69.2 (9.5) Male, % 40.7 36.4 47.9 46.2 63.0 56.4 Structural heart disease at BL, % 72.6 70.6 64.2 60.4 56.1 54.2 Coronary heart disease at BL, % 41.3 37.4 35.1 29.9 26.9 26.1 Any TEAE (serious TEAE), % 72.4 (26.1) 77.6 (24.6) 70.1 (20.1) 73.7 (20.3) 68.1 (20.5) 69.8 (18.4) Death (any cause), % 3.1 3.5 1.6 2.2 1.8 1.1 Any TEAE leading to discontin