Dataset Information

Efficacy and safety of dronedarone by atrial fibrillation history duration: Insights from the ATHENA study.

ABSTRACT: Background: Atrial fibrillation/atrial flutter (AF/AFL) burden increases with increasing duration of AF/AFL history.

Hypothesis: Outcomes with dronedarone may also be impacted by duration of AF/AFL history.

Methods: In this post hoc analysis of ATHENA, efficacy and safety of dronedarone vs placebo were assessed in groups categorized by time from first known AF/AFL episode to randomization (ie, duration of AF/AFL history): <3 months (short), 3 to <24?months (intermediate), and???24?months (long).

Results: Of 2859 patients with data on duration of AF/AFL history, 45.3%, 29.6%, and 25.1% had short, intermediate, and long histories, respectively. Patients in the long history group had the highest prevalence of structural heart disease and were more likely to be in AF/AFL at baseline. Placebo-treated patients in the long history group also had the highest incidence of AF/AFL recurrence and cardiovascular (CV) hospitalization during the study. The risk of first CV hospitalization/death from any cause was lower with dronedarone vs placebo in patients with short (hazard ratio, 0.79 [95% confidence interval: 0.65-0.96]) and intermediate (0.72 [0.56-0.92]) histories; a trend favoring dronedarone was also observed in patients with long history (0.84 [0.66-1.07]). A similar pattern was observed for first AF/AFL recurrence. No new drug-related safety issues were identified.

Conclusions: Patients with long AF/AFL history had the highest burden of AF/AFL at baseline and during the study. Dronedarone significantly improved efficacy vs placebo in patients with short and intermediate AF/AFL histories. While exploratory, these results support the potential value in initiating rhythm control treatment early in patients with AF/AFL.

SUBMITTER: Blomstrom-Lundqvist C

PROVIDER: S-EPMC7724236 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Efficacy and safety of dronedarone by atrial fibrillation history duration: Insights from the ATHENA study.

Blomström-Lundqvist Carina C Marrouche Nassir N Connolly Stuart S Corp Dit Genti Valérie V Wieloch Mattias M Koren Andrew A Hohnloser Stefan H SH

Clinical cardiology 20201020 12

<h4>Background</h4>Atrial fibrillation/atrial flutter (AF/AFL) burden increases with increasing duration of AF/AFL history.<h4>Hypothesis</h4>Outcomes with dronedarone may also be impacted by duration of AF/AFL history.<h4>Methods</h4>In this post hoc analysis of ATHENA, efficacy and safety of dronedarone vs placebo were assessed in groups categorized by time from first known AF/AFL episode to randomization (ie, duration of AF/AFL history): <3 months (short), 3 to <24 months (intermediate), and ...[more]

PMID: 33080088

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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.

Project description:Dronedarone is an amiodarone derivative that was approved in the US in July 2009 to reduce the risk of cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation (AF), who are in sinus rhythm (SR), or who will be cardioverted.This article reviews the pharmacology, adverse effects, and clinical evidence available to date on the use of dronedarone in the management of AF and its potential role in the emergency department setting.In the EURIDIS and ADONIS studies evaluating the efficacy of dronedarone in maintaining SR, dronedarone significantly reduced the risk of recurrence of AF compared to placebo, by 22% and 27%, respectively. The ERATO study examined the ability of dronedarone to control ventricular rate in permanent AF. The DIONYSOS study demonstrated that recurrences of AF were more frequent with dronedarone. However, discontinuation of therapy due to intolerance was more frequent with amiodarone. Furthermore, the ATHENA study demonstrated that dronedarone reduced mortality and cardiovascular hospitalization by 24% (P < 0.05) in patients in SR but with other associated risks and a history of AF. However, the ANDROMEDA study, evaluating the use of dronedarone in patients with recent decompensated heart failure, and the PALLAS study, evaluating the use of dronedarone in patients with chronic AF, were both terminated prematurely due to a trend toward an increased risk of cardiovascular events.Dronedarone has been demonstrated to be effective in reducing the incidence of AF recurrence. It appears to be less effective but better tolerated than amiodarone. Dronedarone appears to have a low proarrhythmic risk and is the first anti-arrhythmic that has been demonstrated to reduce cardiovascular mortality and cardiovascular hospitalization in clinically stable patients with other risk factors for recurrent AF. Therefore, dronedarone can be recommended as an anti-arrhythmic of choice in clinically stable patients for maintaining SR. If dronedarone is to be used in a patient with chronic stable heart failure, the patient must be monitored closely for any worsening of heart failure symptoms. The drug must be discontinued should the heart failure symptoms worsen.

Dataset Information

Efficacy and safety of dronedarone by atrial fibrillation history duration: Insights from the ATHENA study.

Publications

Efficacy and safety of dronedarone by atrial fibrillation history duration: Insights from the ATHENA study.

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