Efficacy and Safety of Dabigatran Compared With Warfarin in Relation to Baseline Renal Function in Patients With Atrial Fibrillation

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. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Sanofi

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Efficacy and safety of dronedarone vs placebo in patients with atrial fibrillation or atrial flutter across a spectrum of renal function: post hoc analyses of the EURIDIS-ADONIS trials

European Heart Journal ◽

10.1093/ehjci/ehaa946.0399 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

M Thind ◽

W Zareba ◽

D Atar ◽

H Crijns ◽

J Zhu ◽

...

Keyword(s):

Atrial Fibrillation ◽

Renal Function ◽

Adverse Events ◽

Atrial Flutter ◽

Cox Regression ◽

Wide Spectrum ◽

Funding Source ◽

Efficacy And Safety ◽

Private Company ◽

Post Hoc

Abstract Background/Introduction The use of antiarrhythmic drugs in patients with chronic kidney disease (CKD) is complex because impaired renal clearance can cause increased drug levels, and risk of intolerance or adverse events. Since CKD commonly co-occurs with atrial fibrillation/atrial flutter (AF/AFL), it is important to establish efficacy and safety for such drugs when used in AF/AFL patients with CKD. Purpose To evaluate the efficacy and safety of dronedarone in patients with AF or AFL across different levels of renal function. Methods This post hoc analysis evaluated pooled data from two multicentre, double-blind, randomised (2:1) trials of rhythm control with dronedarone 400 mg twice daily vs placebo. Primary endpoint was time to first recurrence of AF or AFL. Renal function (estimated glomerular filtration rate [eGFR]) was assessed with the CKD-Epidemiology Collaboration equation. Patients were grouped by eGFR strata. Log-rank testing and Cox regression were used to compare time to events between treatment groups. Results Most (85%) patients had mild or mild-to-moderate decrease in eGFR (Table 1). Median time to first AF recurrence was significantly longer in the dronedarone vs placebo group for all eGFR subgroups except the 30–44 mL/min group (Figure 1), where the trend was consistent; however, the small population size may have precluded meaningful analyses in this subgroup. Serious adverse events, deaths, and treatment discontinuations did not differ notably between each group irrespective of eGFR strata. Conclusions This analysis confirms the efficacy and safety of dronedarone in patients with AF across a wide spectrum of renal function. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Sanofi

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