Title of Trial
DIAMOND-MI

Date and citation of primary publication(s) or References
Lancet 2000;356:2052-2058.

Purpose of the Trial
To investigate whether long-term treatment with dofetilide affects mortality and morbidity in survivors of myocardial infarctions with left ventricular dysfunction.

Study Category
Ventricular arrhythmias/Sudden Death

Patient Population
Patients with recent myocardial infarction and left ventricular dysfunction

Inclusion Criteria

• Age > 18 years
• Myocardial infarction within 7 days
• 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
• Reinfarction
• Arrhythmia requiring treatment and withdrawal of the study drug

Baseline Characteristics
Patient number: 1,510
Mean Age: 69 years
Gender: % female; 26% females
Other characteristics: 7% of patients enrolled had atrial fibrillation at randomization

Years to Follow-up
Median follow-up was 456 days

Results
No significant differences were found between the dofetilide and placebo groups in all-cause mortality (31% versus 32%), cardiac mortality (26% versus 28%), or total arrhythmic deaths (17% versus 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 versus 7 of 56; p=0.002). There were seven cases of torsade de pointes ventricular tachycardia, all in the dofetilide group.

Sponsors
Pfizer Central Research

Trial Status: Completed

Review written by Samir Saba, MD