In patients with atrial fibrillation (AF) and atrial flutter (AFL) both with and without diabetes, treatment with the multichannel blocking antiarrhythmic agent dronedarone has demonstrated efficacy in reducing cardiovascular (CV) hospitalization rates, delaying time to initial CV hospitalization and death, as well as reducing the recurrence of AF and AFL. These findings were published in the Journal of Diabetes and Its Complications.

A post hoc analysis was conducted among patients from the ATHENA study ( identifier: NCT00174785), the EURIDIS study ( identifier: NCT00259428), and the ADONIS study ( identifier: NCT00259376). The EURIDIS and ADONIS trials shared the same study design and protocol, but they were conducted in different geographic locales. EURIDIS was conducted in Europe and Africa; ADONIS in North America, Australia, and Africa.

In ATHENA, patients could either be in sinus rhythm or in AF or AFL at randomization, but with evidence of both AF and AFL and sinus rhythm in the last 6 months prior to randomization. In EURIDIS and ADONIS, patients had to be in sinus rhythm for 1 hour or longer prior to randomization. Patients were randomly assigned to double-blind treatment with dronedarone 400 mg twice daily or placebo in the ATHENA (1:1 ratio) and EURIDIS and ADONIS (2:1 ratio) studies.

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The main study outcome measures in ATHENA were time to first hospitalization for a CV cause or death from any cause and time to first documented AF or AFL event recurrence. In EURIDIS and ADONIS, the main outcome measure was time to the first documented AF or AFL recurrence within 12 months. In ATHENA, any unplanned hospitalization, such as admission with an overnight stay in the hospital that covered at least 2 days, was categorized according to the cause and was divided into CV or non-CV.

Of the 4628 patients in ATHENA, 945 had diabetes, with 482 of these individuals treated with dronedarone and 463 with placebo. Of the 1237 patients in EURIDIS and ADONIS, 215 had diabetes, with 148 of these individuals treated with dronedarone and 67 with placebo.

In the ATHENA study, higher rates of CV hospitalization and death were reported among patients with diabetes compared with those without diabetes (39.5% vs 34.7%, respectively). In this study, among participants both with and without diabetes, significantly lower rates of CV hospitalizations and deaths were reported in the dronedarone-treated group than in the placebo-treated group (hazard ratio [HR], 0.75; 95% CI, 0.61-0.91; P =.005 in those with diabetes vs HR, 0.76; 95% CI, 0.68-0.85; P <.0001 in those without diabetes). The incidence of first CV hospitalization or death was lower among participants with diabetes treated with dronedarone compared with those treated with placebo (35.1% vs 44.1%, respectively).

In participants with diabetes, the median AF or AFL recurrence time was significantly longer in dronedarone-treated patients than in placebo-treated patients (ATHENA: 722 days vs 527 days, respectively; log-rank  P =.004; EURIDIS/ADONIS: 100 days vs 23 days, respectively, log-rank P =.15). Further, in participants without diabetes, the median AF or AFL recurrence time also was significantly longer in dronedarone-treated patients than in placebo-treated patients (ATHENA: 741 days vs 492 days, respectively; log-rank P <.0001; EURIDIS/ADONIS: 120 days vs 59 days, respectively; log-rank P =.0002).

Several limitations exist regarding the current study. Since this was a nonspecified, exploratory post hoc analysis, patients were not stratified to treatment based on their status of having or not having diabetes. No systematic data were available on blood glucose levels observed during ATHENA or whether the treatment of patients’ diabetes changed following enrollment in any of the studies. The diagnosis of diabetes differed slightly between ATHENA and EURIDIS and ADONIS.

“Further studies to understand the relationship between the major cardiometabolic conditions of AF and diabetes can help in understanding the role of dronedarone treatment in early disease management,” the study authors wrote.

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Handelsman Y, Bunch TJ, Rodbard, et al. Impact of dronedarone on patients with atrial fibrillation and diabetes: a sub-analysis of the ATHENA and EURIDIS/ADONIS studies. J Diabetes Complications. Published online June 8, 2022. doi:10.1016/j.jdiacomp.2022.108227 

This article originally appeared on The Cardiology Advisor