Increased mortality after dronedarone therapy for severe heart failure.
BACKGROUND
Dronedarone is a novel antiarrhythmic drug with electrophysiological properties that are similar to those of amiodarone, but it does not contain iodine and thus does not cause iodine-related adverse reactions. Therefore, it may be of value in the treatment of patients with heart failure.


METHODS
In a multicenter study with a double-blind design, we planned to randomly assign 1000 patients who were hospitalized with symptomatic heart failure and severe left ventricular systolic dysfunction to receive 400 mg of dronedarone twice a day or placebo. The primary end point was the composite of death from any cause or hospitalization for heart failure.


RESULTS
After inclusion of 627 patients (310 in the dronedarone group and 317 in the placebo group), the trial was prematurely terminated for safety reasons, at the recommendation of the data and safety monitoring board, in accordance with the board's predefined rules for termination of the study. During a median follow-up of 2 months, 25 patients in the dronedarone group (8.1%) and 12 patients in the placebo group (3.8%) died (hazard ratio in the dronedarone group, 2.13; 95% confidence interval [CI], 1.07 to 4.25; P=0.03). The excess mortality was predominantly related to worsening of heart failure--10 deaths in the dronedarone group and 2 in the placebo group. The primary end point did not differ significantly between the two groups; there were 53 events in the dronedarone group (17.1%) and 40 events in the placebo group (12.6%) (hazard ratio, 1.38; 95% CI, 0.92 to 2.09; P=0.12). More increases in the creatinine concentration were reported as serious adverse events in the dronedarone group than in the placebo group.


CONCLUSIONS
In patients with severe heart failure and left ventricular systolic dysfunction, treatment with dronedarone was associated with increased early mortality related to the worsening of heart failure. (ClinicalTrials.gov number, NCT00543699.)
Køber
Lars
L
Department of Cardiology, Rigshospitalet, University of Copenhagen, Denmark. lk@heart.dk
Torp-Pedersen
Christian
C
McMurray
John J V
JJ
Gøtzsche
Ole
O
Lévy
Samuel
S
Crijns
Harry
H
Amlie
Jan
J
Carlsen
Jan
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000638:Amiodarone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000401:mortality; D002423:Cause of Death; D004311:Double-Blind Method; D000077764:Dronedarone; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D017211:Treatment Failure; D018487:Ventricular Dysfunction, Left
D000889:Anti-Arrhythmia Agents; D000077764:Dronedarone; D000638:Amiodarone