What is the clinical evidence from this study?

Study design: RCT. Population: Atrial fibrillation with stable congestive heart failure (n=209). Intervention: Dronedarone vs. Placebo. Primary outcome: Time to first cardiovascular (CV) hospitalization or death (HR 0.78, 95% CI 0.52 - 1.16).

What does this research mean for the field?

In patients with atrial fibrillation and stable congestive heart failure, dronedarone does not increase mortality and reduces cardiovascular hospitalization or death similarly to the overall AF population, though it remains contraindicated in unstable or severe CHF. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To evaluate the efficacy and safety of dronedarone on cardiovascular mortality and morbidity in patients with atrial fibrillation and stable congestive heart failure.

August 23, 2026European Heart Journal72 citationsOpen Access

Dronedarone in patients with congestive heart failure: insights from ATHENA

SHS. H. Hohnloser HCHarry J.G.M. Crijns MEMartin van Eickels

Key Result

In patients with atrial fibrillation and stable NYHA class II/III congestive heart failure, dronedarone did not increase mortality and showed a trend towards reducing cardiovascular hospitalization or death (HR 0.78).

Key Points

To evaluate the efficacy and safety of dronedarone on cardiovascular mortality and morbidity in patients with atrial fibrillation and stable congestive heart failure.
Post hoc subgroup analysis of the ATHENA randomized, placebo-controlled trial evaluating 209 patients with NYHA class II/III congestive heart failure and left ventricular ejection fraction ≤0.40 (114 placebo, 95 dronedarone) within a total cohort of 4,628 patients with paroxysmal or persistent atrial fibrillation.
The primary outcome was time to first cardiovascular hospitalization or death.
The primary outcome occurred in 42 of 95 dronedarone patients compared with 59 of 114 placebo patients (HR 0.78, 95% CI 0.52–1.16).
All-cause mortality occurred in 12 of 95 dronedarone patients versus 20 of 114 placebo patients (HR 0.71, 95% CI 0.34–1.44), and hospitalizations for NYHA class IV episodes occurred in 42 dronedarone versus 54 placebo patients (HR 0.78, 95% CI 0.52–1.17).

Study Design

Type

RCT (n=209)

Blinding

Double-blind

Randomization

Randomized

Multicenter

Yes

Structured PICO

Does dronedarone reduce cardiovascular hospitalization or death in patients with atrial fibrillation and stable congestive heart failure?

Population

209 patients with paroxysmal or persistent atrial fibrillation and stable NYHA class II/III congestive heart failure with LVEF ≤0.40, analyzed post hoc from the ATHENA trial.

Intervention

Dronedarone 400 mg oral twice daily

Comparator

Matching placebo

Outcome

Time to first cardiovascular (CV) hospitalization or deathcomposite

In patients with atrial fibrillation and stable congestive heart failure, dronedarone did not increase mortality and showed a trend toward reducing cardiovascular hospitalization or death, contrasting with its known harmful effects in unstable heart failure.

Main Result

Hazard Ratio: 0.78 (95% CI 0.52–1.16)

Absolute Event Rate: 44.2% vs 51.8%

Limitations

Exploratory efficacy analyses comprising relatively small subgroups have inherent limitations that result from the loss of a randomization effect.
Interaction analyses may be underpowered given the small patient numbers in some of the subgroups.
Exploratory efficacy analyses comprising relatively small subgroups have inherent limitations that result from the loss of a randomization effect
Interaction analyses may be underpowered given the small patient numbers in some of the subgroups

Abstract

AIMS: Dronedarone is a new multichannel blocking antiarrhythmic drug for treatment of atrial fibrillation (AF). In patients with recently decompensated congestive heart failure (CHF) and depressed LV function, the drug was associated with excess mortality compared with a placebo group. The present study aimed to analyse in detail the effects of dronedarone on mortality and morbidity in AF patients CHF. METHODS AND RESULTS: We performed a post hoc analysis of ATHENA, a large placebo-controlled outcome trial in 4628 patients with paroxysmal or persistent AF, to evaluate the relationship between clinical outcomes and dronedarone therapy in patients with stable CHF. The primary outcome was time to first cardiovascular (CV) hospitalization or death. There were 209 patients with NYHA class II/III CHF and a left ventricular ejection fraction < or =0.40 at baseline (114 placebo, 95 dronedarone patients). A primary outcome event occurred in 59/114 placebo patients compared with 42/95 dronedarone patients hazard ratio (HR) 0.78, 95% CI = 0.52-1.16. Twenty of 114 placebo patients and 12/95 dronedarone patients died during the study (HR 0.71, 95% CI = 0.34-1.44). Fifty-four placebo and 42 dronedarone patients were hospitalized for an intermittent episode of NYHA class IV CHF (HR = 0.78, 95% CI = 0.52-1.17). CONCLUSION: In this post-hoc analysis of ATHENA patients with AF and stable CHF, dronedarone did not increase mortality and showed a reduction of CV hospitalization or death similar to the overall population. However, in the light of the ANtiarrhythmic trial with DROnedarone in Moderate to severe CHF Evaluating morbidity DecreAse study, dronedarone should be contraindicated in patients with NYHA class IV or unstable NYHA classes II and III CHF.

Expert Takes6 quotes

1/6

“The results of these two studies can't possibly be more different, both with respect to death and the effect on hospitalization. Differences between the ANDROMEDA and ATHENA trials may have been due to the fact that there was virtually no overlap in the types of patients enrolled in the two studies.”

Milton Packer, Cardiologist, UT Southwestern Medical CenterUniversity of Texas Southwestern Medical Centerauto_pipelineSupportiveView source

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