english.prescrire.org > Spotlight > Archives : 2010 > Dronedarone in atrial fibrillation: too many questions about long-term adverse effects

Spotlight: Archives

Every month, the subjects in Prescrire’s Spotlight.

2010 : 1 | 30 | 60 | 90

Dronedarone in atrial fibrillation: too many questions about long-term adverse effects

FEATURED REVIEW In patients with atrial fibrillation, dronedarone has less antiarrhythmic efficacy than amiodarone but fewer short-term adverse effects. Little is known of potential long-term adverse effects, but dronedarone has been linked to increased mortality in patients with heart failure.  When antiarrhythmic drug therapy is needed, it is better to continue to use a beta blocker or, as a last resort, amiodarone, a drug with better-documented adverse effects, especially during long-term treatment.  
Full review (4p) available for download by subscribers.

Abstract

  • In patients with atrial fibrillation, a beta blocker is generally used initially to prevent recurrence or to slow the heart rate. Amiodarone is a last resort, mainly because of its numerous adverse effects.
     
  • Dronedarone, chemically similar to amiodarone, was recently authorised for this indication in the European Union.
     
  • In a double-blind trial versus amiodarone in 504 patients, the failure rate was significantly higher with drone darone (75.1% versus 58.8%).
     
  • Two placebo-controlled trials in heart failure patients yielded conflicting results. Dronedarone was associated with a statistically significant increase in mortality in a trial in 627 symptomatic patients free of arrhythmias. However, there was no statistically significant difference in a trial including 4630 patients with atrial fibrillation and a lower risk of cardiovascular events. 
     
  • There are no comparative trials versus other antiarrhythmic drugs or heart-rate-lowering agents, including betablockers and calcium channel blockers.
     
  • Like other antiarrhythmic drugs, dronedarone also has arrhythmogenic effects, including bradycardia and QT prolongation. Other adverse effects include diarrhoea, nausea and vomiting, and cutaneous disorders. Transient elevation of creatinine levels is also frequent, and cases of renal failure have been reported.  
     
  • In the trial versus amiodarone, dronedarone had a different pattern of short-term adverse effects, including more gastrointestinal disorders but less frequent thyroid disorders, neurological disorders, hypersensitivity reactions, hypertension, and QT prolongation. Little is known of potential long-term adverse effects, especially pulmonary fibrosis. 
     
  • In practice, dronedarone is better tolerated but less effective than amiodarone in the short term. When antiarrhythmic drug therapy is needed, it is better to continue to use a beta blocker or, as a last resort, amiodarone, a drug with better-documented adverse effects, especially during long-term treatment.  

©Prescrire August 2010

"Dronedarone in atrial fibrillation: too many questions about long-term adverse effects" Prescrire Int 2010; 19 (108): 149-452 (pdf, subscribers only).
Download full review