Dataset Information

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:

Aims

Use of antiarrhythmic drugs (AADs) in patients with chronic kidney disease (CKD) is challenging owing to issues with renal clearance, drug accumulation, and increased proarrhythmic risks. Because CKD is a common comorbidity in patients with atrial fibrillation/atrial flutter (AF/AFL), it is important to establish the efficacy and safety of AAD treatment in patients with CKD.

Methods and results

Dronedarone efficacy and safety in individuals with AF/AFL and varying renal functionality [estimated glomerular filtration rate (eGFR): ≥60, ≥45 and <60, and <45 mL/min] was investigated in a post hoc analysis of ATHENA (NCT00174785), a randomized, double-blind trial of dronedarone vs. placebo in patients with paroxysmal or persistent AF/AFL plus additional cardiovascular (CV) risk factors. Log-rank testing and Cox regression were used to compare the incidence of endpoints between treatments. Overall, 4588 participants were enrolled from the trial. There was no interaction between treatment group and baseline eGFR assessed as a continuous variable (P = 0.743) for the first CV hospitalization or death from any cause (primary outcome). This outcome was lower with dronedarone vs. placebo across a wide range of renal function. First CV hospitalization and first AF/AFL recurrence were both lower in the two least renally impaired subgroups with dronedarone vs. placebo. Treatment emergent adverse events leading to treatment discontinuation were more frequent with dronedarone vs. placebo and occurred more often in patients with severe renal impairment.

Conclusion

Dronedarone is an effective AAD in patients with AF/AFL and CV risk factors across a wide range of renal function.

SUBMITTER: Vamos M

PROVIDER: S-EPMC9175188 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

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.

Vamos Mate M Oldgren Jonas J Nam Gi-Byoung GB Lip Gregory Y H GYH Calkins Hugh H Zhu Jun J Ueng Kwo-Chang KC Ludwigs Ulf U Wieloch Mattias M Stewart John J Hohnloser Stefan H SH

European heart journal. Cardiovascular pharmacotherapy 20220601 4

<h4>Aims</h4>Use of antiarrhythmic drugs (AADs) in patients with chronic kidney disease (CKD) is challenging owing to issues with renal clearance, drug accumulation, and increased proarrhythmic risks. Because CKD is a common comorbidity in patients with atrial fibrillation/atrial flutter (AF/AFL), it is important to establish the efficacy and safety of AAD treatment in patients with CKD.<h4>Methods and results</h4>Dronedarone efficacy and safety in individuals with AF/AFL and varying renal funct ...[more]

PMID: 34958366

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Project description:BackgroundThe ATHENA (A Placebo-Controlled, Double-Blind, Parallel Arm Trial to Assess the Efficacy of Dronedarone 400 mg bid for the Prevention of Cardiovascular Hospitalization or Death from Any Cause in Patients with Atrial Fibrillation/Atrial Flutter) trial demonstrated a significant reduction (26%) in the rate of first cardiovascular (CV) hospitalization in dronedarone-treated patients with paroxysmal or persistent atrial fibrillation/flutter (AF/AFL). ATHENA was the first trial to demonstrate a CV outcomes benefit, specifically reduced CV hospitalizations, with an antiarrhythmic drug. The objective of this study was to assess the impact of dronedarone treatment on healthcare resource utilization among real-world patients with AF/AFL in United States clinical practice.MethodsThis retrospective cohort study used claims data from the MarketScan® databases (Truven Health, Durham, NC, USA) to identify patients with ≥2 concurrent de novo pharmacy claims for dronedarone (≥180 days' total supply) between June 2009 and March 2011, and with an AF/AFL diagnosis and no heart failure-related hospitalization during the 12 months preceding the initial (index) dronedarone claim. Annualized inpatient and outpatient resource utilization were compared between the pre-index (baseline) and post-index (follow-up) periods.ResultsIn total, 5,656 AF/AFL patients were prescribed dronedarone for ≥6 months and were followed for mean (standard deviation) 11.9 (4.7) months. Reductions in mean numbers of annualized all-cause, CV- and AF-related hospitalizations (~40-45%), and emergency department visits (~30-45%) were realized. These benefits were offset by increases in office visits (~10-30%) and AF-related prescription claims (74%) after dronedarone initiation. The sub-cohort of patients switching to dronedarone from Prior Rhythm-Control therapy (n=2,080) showed similar reductions in hospital and emergency department events.ConclusionsThis study suggests that dronedarone use in real-world practice, as in the ATHENA trial, results in substantial reductions in hospital admissions, both in first-line and second-line antiarrhythmic treatment settings.

Project description:AimsLimited therapeutic options are available for the management of atrial fibrillation/flutter (AF/AFL) with concomitant heart failure (HF) with preserved (HFpEF) and mildly reduced ejection fraction (HFmrEF). Dronedarone reduces the risk of cardiovascular events in patients with AF, but sparse data are available examining its role in patients with AF complicated by HFpEF and HFmrEF.Methods and resultsATHENA was an international, multicentre trial that randomized 4628 patients with paroxysmal or persistent AF/AFL and cardiovascular risk factors to dronedarone 400 mg twice daily versus placebo. We evaluated patients with (i) symptomatic HFpEF and HFmrEF (defined as left ventricular ejection fraction [LVEF] >40%, evidence of structural heart disease, and New York Heart Association class II/III or diuretic use), (ii) HF with reduced ejection fraction (HFrEF) or left ventricular dysfunction (LVEF ≤40%), and (iii) those without HF. We assessed effects of dronedarone versus placebo on death or cardiovascular hospitalization (primary endpoint), other key efficacy endpoints, and safety. Overall, 534 (12%) had HFpEF or HFmrEF, 422 (9%) had HFrEF or left ventricular dysfunction, and 3672 (79%) did not have HF. Patients with HFpEF and HFmrEF had a mean age of 73 ± 9 years, 37% were women, and had a mean LVEF of 57 ± 9%. Over a mean follow-up of 21 ± 5 months, dronedarone consistently reduced risk of death or cardiovascular hospitalization (hazard ratio 0.76; 95% confidence interval 0.69-0.84) without heterogeneity based on HF status (pinteraction >0.10). This risk reduction in the primary endpoint was consistent across the range of LVEF (as a continuous function) in HF without heterogeneity (pinteraction = 0.71). Rates of death, cardiovascular hospitalization, and HF hospitalization each directionally favoured dronedarone versus placebo in HFpEF and HFmrEF, but these treatment effects were not statistically significant in this subgroup.ConclusionsDronedarone is associated with reduced cardiovascular events in patients with paroxysmal or persistent AF/AFL and HF across the spectrum of LVEF, including among those with HFpEF and HFmrEF. These data support a rationale for a future dedicated and powered clinical trial to affirm the net clinical benefit of dronedarone in this population.

Dataset Information

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.

Aims

Methods and results

Conclusion

Publications

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.

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