Effect of dofetilide in patients with recent myocardial infarction and left-ventricular dysfunction: a randomised trial.
BACKGROUND
Arrhythmias cause much morbidity and mortality after myocardial infarction, but in previous trials, antiarrhythmic drug therapy has not been convincingly effective. Dofetilide, a new class III agent, was investigated for effects on all-cause mortality and morbidity in patients with left-ventricular dysfunction after myocardial infarction.


METHODS
In 37 Danish coronary-care units, 1510 patients with severe left-ventricular dysfunction (wall motion index < or = 1.2, corresponding to ejection fraction < or = 0.35) were enrolled in a randomised, double-blind study comparing dofetilide (n=749) with placebo (n=761). The primary endpoint was all-cause mortality. Secondary endpoints included cardiac and arrhythmic mortality and total arrhythmic deaths. Analyses were by intention to treat.


RESULTS
No significant differences were found between the dofetilide and placebo groups in all-cause mortality (230 [31%] vs 243 [32%]), cardiac mortality (191 [26%] vs 212 [28%]), or total arrhythmic deaths (129 [17%] vs 140 [18%]). Atrial fibrillation or flutter was present in 8% of the patients at study entry. In these patients, dofetilide was significantly better than placebo at restoring sinus rhythm (25 of 59 vs seven of 56; p=0.002). There were seven cases of torsade de pointes ventricular tachycardia, all in the dofetilide group.


CONCLUSIONS
In patients with severe left-ventricular dysfunction and recent myocardial infarction, treatment with dofetilide did not affect all-cause mortality, cardiac mortality, or total arrhythmic deaths. Dofetilide was effective in treating atrial fibrillation or flutter in this population.
Køber
L
L
Department of Cardiology, Gentofte University Hospital, Hellerup, Denmark. lk@heart.dk
Bloch Thomsen
P E
PE
Møller
M
M
Torp-Pedersen
C
C
Carlsen
J
J
Sandøe
E
E
Egstrup
K
K
Agner
E
E
Videbaek
J
J
Marchant
B
B
Camm
A J
AJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy; D001282:Atrial Flutter / Q000150:complications / Q000188:drug therapy; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000401:mortality* / Q000503:physiopathology; D010627:Phenethylamines / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy*
D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D013449:Sulfonamides; C063533:dofetilide