Title of Trial
DIAMOND-CHF

Date and citation of primary publication(s) or References
New England Journal of Medicine 1999; 341(12): 857-865.

Purpose of the Trial
To investigate whether dofetilide affects survival or morbidity among patients with reduced left ventricular function and congestive heart failure.

Study Category
Ventricular arrhythmias/Sudden Death

Patient Population
Patients with congestive heart failure and left ventricular dysfunction

Inclusion Criteria

• Age > 18 years
• Class III-IV NYHA congestive heart failure
• Prior myocardial infarction
• Left ventricular ejection fraction < 35%
• Provide written informed consent

Exclusion Criteria

• Women of childbearing potential not on contraceptives
• Myocadial infarction within 7 days
• Heart rate < 50 beats/ minute when awake
• Sinoatrial block or second- or third-degree atrioventricular block not treated with a pacemaker
• History of drug-induced proarrhythmia
• Corrected QT interval that exceeded 460 ms (500 ms in cases of bundle-branch block), or diastolic or systolic blood pressures >115 or <80 mm Hg
• Patients also were excluded who were likely to die from other causes during the study
• Serum potassium levels of <3.6 mEq/L (<3.6 mmol/L) or >5.5 mEq/L (>5.5 mmol/L)
• Treatment with class I or III antiarrhythmic drugs or had participated in experimental drug studies in the previous 3 months
• Creatinine clearance rates of <20 mL/min
• Serious liver dysfunction, acute myocarditis, planned cardiac surgery or angioplasty, aortic stenosis, cardiac surgery within the prior 4 weeks, or the presence of an implantable defibrillator.

Study Design
Randomized, double-blind, placebo-controlled, multicenter study

Primary Endpoint
Death from any cause

Secondary Endpoints

• Cardiac death
• Arrhythmic death
• Cardiac death or successful resuscitation after cardiac arrest
• Worsening heart failure
• Myocardial infarction

Baseline Characteristics
Patient number: 1,518
Mean Age: 70 years
Gender: % female; 26% females
Other characteristics: 26% of patients enrolled had atrial fibrillation

Years to Follow-up
Median follow-up was 18 months

Results
There were no differences between the dofetilide group and the placebo group in all-cause mortality (41% versus 42%, hazard ratio=0.95 (0.81-1.11)). Treatment with dofetilide significantly reduced the risk of hospitalization for heart failure (hazard ratio=0.75 (0.63-0.89)). Dofetilide was effective in converting atrial fibrillation into sinus rhythm (12% versus 1% at one month) and in maintaining sinus rhythm once it was restored (hazard ratio for recurrence of atrial fibrillation=0.35 (0.22-0.57)).

Sponsors
Pfizer Central Research

Trial Status: Completed

Review written by Samir Saba, MD