Survival after withdrawal of dofetilide in patients with congestive heart failure and a short baseline QTc interval; a follow-up on the Diamond-CHF QT substudy.
BACKGROUND
We have previously observed dofetilide to be associated with improved survival when the pre-treatment baseline QTc interval was below 429 ms. In this study we tested the natural extension of this observation-that the same group of patients should have a loss of survival benefit after withdrawal of dofetilide.


METHODS
Patients with congestive heart failure (CHF) and reduced left ventricular function enrolled in the Diamond-CHF (Danish Investigations of Arrhythmia and Mortality on Dofetilide-CHF) study were eligible for our QT substudy provided they were in sinus rhythm and had a measurable QTc interval from a 12-lead standard ECG taken before randomization to placebo or dofetilide. An extended follow-up was performed from study closure, December 1996 until August 2001.


RESULTS
Of the 418 patients entering the extended follow-up, 215 (51%) patients died during this 4.5 years of additional observation time. The baseline QTc interval made no prognostic difference to mortality in placebo treated patients. For dofetilide treated patients with a baseline QTc interval <429 ms, increased mortality was observed during the extended follow-up compared to placebo (risk ratio 1.5, 95% confidence interval 1.1-2.8)[corrected].


CONCLUSIONS
This follow-up study shows significant loss of survival benefit upon withdrawal of dofetilide in patients with CHF and a pre-treatment QTc interval below 429 ms. An independent randomized trial is warranted to validate these results.
Brendorp
B
B
Department of Cardiology, Copenhagen University Hospital, Gentofte, Denmark. bb@heart.dk
Torp-Pedersen
C
C
Elming
H
H
Køber
L
L
D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007231:Infant, Newborn; D008133:Long QT Syndrome / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010627:Phenethylamines / Q000008:administration & dosage*; D016016:Proportional Hazards Models; D012307:Risk Factors; D013449:Sulfonamides / Q000008:administration & dosage*; D016019:Survival Analysis; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000401:mortality
D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D013449:Sulfonamides; C063533:dofetilide