Dataset Information

Effects of dronedarone started rapidly after amiodarone discontinuation.

ABSTRACT:

Background

Multiple studies have shown that amiodarone is effective in treating atrial fibrillation (AF), but is associated with a relatively high incidence of side effects; however, due to amiodarone's long elimination half-life (20-100 days), physicians may hesitate to start other drugs until it has fully cleared.

Hypothesis

A rapid switch from amiodarone to dronedarone is feasible.

Methods

EURIDIS and ADONIS were double-blind, multinational, parallel-group trials comparing the efficacy and safety of dronedarone with placebo over 12 months. This retrospective subanalysis of EURIDIS/ADONIS compared the effects of dronedarone in patients discontinuing amiodarone within 2 days before randomization ("rapid switch") with results in patients who had received no amiodarone during the 2 months preceding randomization.

Results

In total, 1237 patients were enrolled ("rapid switch", n = 154; "no amiodarone", n = 1014). In both the "rapid switch" and the "no amiodarone" groups, dronedarone users had significantly lower AF recurrence than patients receiving placebo (HR = 0.64, 95% CI, 0.44-0.95; P = 0.0224 and HR = 0.79, 95% CI, 0.67-0.92; P = 0.0027, respectively). Dronedarone users had a higher incidence of bradyarrhythmic events than placebo-treated patients. A "rapid switch" from amiodarone to dronedarone was associated with a higher incidence of serious heart failure events and heart failure hospitalizations versus all other groups. Overall event rates were low and there was no significant difference in total adverse event rates or deaths between groups.

Conclusion

In this patient population, a switch from amiodarone to dronedarone within a 2-day time frame might be feasible in certain patient categories, but further investigation is warranted.

SUBMITTER: Immordino L

PROVIDER: S-EPMC6649410 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Publications

Effects of dronedarone started rapidly after amiodarone discontinuation.

Immordino Laura L Connolly Stuart S Crijns Harry H Roy Denis D Capucci Alessandro A Radzik David D Aliot Etienne E Hohnloser Stefan S Kowey Peter P

Clinical cardiology 20130121 2

<h4>Background</h4>Multiple studies have shown that amiodarone is effective in treating atrial fibrillation (AF), but is associated with a relatively high incidence of side effects; however, due to amiodarone's long elimination half-life (20-100 days), physicians may hesitate to start other drugs until it has fully cleared.<h4>Hypothesis</h4>A rapid switch from amiodarone to dronedarone is feasible.<h4>Methods</h4>EURIDIS and ADONIS were double-blind, multinational, parallel-group trials compari ...[more]

PMID: 23338943

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Project description:Amiodarone reversibly decreases sodium-iodide symporter mRNA expression at therapeutic concentrations and induces antioxidant responses at supraphysiological concentrations in cultured human thyroid follicles Amiodarone, a potent antiarrhythmic agent, is a highly active oxidant, exerting cytotoxic effects on thyrocytes at pharmacological concentrations. Patients receiving amiodarone usually remain euthyroid, but occasionally develop thyroid dysfunction, such as amiodarone-associated hypothyroidism or amiodarone-induced thyrotoxicosis. To elucidate the mechanism by which amiodarone elicits thyroid dysfunction, human thyroid follicles were cultured with TSH and amiodarone at therapeutic (1-2 microM) and pharmacological (10-20microM) concentrations, and the drug-induced effect on whole human gene expression was analyzed by cDNA microarray. Amiodarone at 1-2microM decreased the expression level of the sodium-iodide symporter (NIS) to nearly half, but did not affect genes participating in thyroid hormonogenesis (thyroid peroxidase, thyroglobulin, pendrin, NADPH oxidase). Higher concentrations (10-20 microM) decreased the expression of all these genes, accompanied by increased expression of antioxidant proteins such as heme oxygenase 1 and ferritin. When thyroid follicles obtained from a patient with Graves’ disease who had been treated with amiodarone for 2 months before thyroidectomy were cultured in amiodarone-free medium, TSH-induced thyroid function was intact, suggesting that amiodarone at a maintenance dose did not elicit any cytotoxic effect on thyrocytes. The ultrastructural features of cultured thyroid follicles were compatible with these in vitro findings. These in vitro and ex vivo findings suggest that patients taking maintenance doses of amiodarone usually remain euthyroid, probably due to escape from the Wolff-Chaikoff effect mediated by decreased expression of NIS mRNA. Furthermore, amiodarone is not cytotoxic for thyrocytes at therapeutic concentrations but elicits cytotoxicity through oxidant activity at supra-physiological concentrations. Keywords: Cultured human thyroid follicles

Dataset Information

Effects of dronedarone started rapidly after amiodarone discontinuation.

Background

Hypothesis

Methods

Results

Conclusion

Publications

Effects of dronedarone started rapidly after amiodarone discontinuation.

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