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Danish Investigations of Arrhythmia and Mortality on Dofetilide - DIAMOND
Description:
Dofetilide for atrial arrhythmias in patients at risk for sudden death.
Hypothesis:
To test the prophylactic use of the selective potassium-channel blocker, dofetilide, in patients at high risk of sudden death.
Study Design
Study Design:
Patients Screened: 14,500 (5,812 CHF; 8,688 MI)
Patients Enrolled: 3,028
Mean Follow Up: 17 months
Mean Patient Age: 72
Female: 23
Patient Populations:
Impaired LV function (EF≤35%) determined by echocardiography
Patients admitted to hospital with congestive heart failure (CHF) [DIAMOND-CHF]
Acute myocardial infarction (MI) within the previous 7 days [DIAMOND-MI]
Primary Endpoints:
Conversion of atrial arrhythmias to sinus rhythm
Secondary Endpoints:
Long-term maintenance of sinus rhythm;
Safety and tolerance of dofetilide
All-cause mortality
Drug/Procedures Used:
250 mcg/b.i.d. dofetilide vs. matching placebo
Principal Findings:
Between November 1993 and July 1996, 1518 patients were included in the CHF study and 1510 patients in the MI study. Overall 1-year mortality of randomized patients were 28 and 22%, respectively. Long-term follow-up is underway.
A combined analyses evaluated 506 patients with atrial fibrillation or atrial flutter (115 from DIAMOND MI and 391 from DIAMOND CHF), approximately 60% of whom were in New York Heart Association class III or IV at baseline. Previously reported DIAMOND data (Clin Cardiol 1997;20:704-10) found a neutral effect on mortality and a reduction in hospitalizations for congestive heart failure through formal equivalence testing.
At the end of the first month, 22% (56/249) of patients on dofetilide had converted to normal sinus rhythm (NSR) vs. 3% (7/257) on placebo (p<0.001). At the end of the first year, 43% of the dofetilide group converted to NSR with pharmacotherapy alone vs. 15% in the placebo group. In addition, similar numbers of patients in each group converted to NSR via direct current (DC) cardioversion (12% dofetilide vs. 14% placebo). Of those converted, significantly more patients in the dofetilide group maintained NSR during over 3 years of follow-up compared to the placebo group (80% vs. 40%, p<0.001). However, again there was no difference in mortality between the patient groups, which is likely due to the fact the study was not powered to demonstrate an effect on mortality.
Dofetilide was well-tolerated and produced no deaths. Only 4 (1.6%) cases of torsades de pointes were reported during the first year of active therapy, a low figure compared to other antiarrhythmic drugs. The numbers of patients suffering stroke/embolism or requiring resuscitation for cardiac arrest was similar in both groups.
Interpretation:
For patients with severe left ventricular dysfunction, dofetilide is effective in converting atrial fibrillation or flutter to NSR and maintaining NSR over time compared to placebo. Early survival data is promising in an area where other anti-arrhythmic agents have been disappointing; long-term outcomes are forthcoming.
References:
1. Clin Cardiol 1997;20:704-10. Rationale and study design
2. Circulation 1998;98(Suppl I):I-632-3. Efficacy in atrial fibrillation
Keywords: Myocardial Infarction, Stroke, Resuscitation, Follow-Up Studies, Potassium Channel Blockers, Electric Countershock, Death, Sudden, Phenethylamines, Heart Arrest, Torsades de Pointes, Heart Failure, Embolism, Ventricular Dysfunction, Left, Sulfonamides, Echocardiography
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