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Effect of indecainide in patients with left ventricular dysfunction
E V Giardina1, A L Saroff, M Schneider
1Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Insights
Indecainide effectively suppressed ventricular arrhythmias in patients with heart disease. Careful monitoring is advised for patients with reduced renal function or ejection fraction due to higher drug concentrations.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Cardiac arrhythmias pose significant risks, especially in patients with underlying heart disease and impaired left ventricular function.
- Type Ic antiarrhythmic agents are used to manage ventricular arrhythmias.
Purpose of the Study:
- To evaluate the efficacy and safety of indecainide, a type Ic antiarrhythmic agent, in patients with heart disease and significant ventricular premature complexes.
- To determine the relationship between indecainide dosage, serum concentration, and electrocardiographic changes.
Main Methods:
- Eleven patients with heart disease and frequent ventricular premature complexes received oral indecainide, with dosage titration based on efficacy and tolerability.
- Ventricular premature complexes and ventricular tachycardia episodes were monitored.
- Serum drug concentrations and electrocardiographic parameters (PR, QRS, QT, QTc intervals) were analyzed.
Main Results:
- Indecainide achieved greater than or equal to 80% suppression of ventricular premature complexes in 91% of patients and complete suppression of ventricular tachycardia in 5 of 8 patients.
- Effective mean daily indecainide dose was 191 +/- 32 mg. Efficacy was often achieved at serum concentrations >= 600 ng/ml.
- Serum drug concentration correlated with gender, creatinine clearance, and ejection fraction. Indecainide prolonged PR and QRS intervals, with a linear relationship to serum drug concentration.
Conclusions:
- Indecainide demonstrates significant efficacy in suppressing ventricular arrhythmias in patients with heart disease and left ventricular dysfunction.
- Dosage and monitoring should be individualized, particularly in patients with compromised renal function or reduced ejection fraction, due to potential for higher serum drug concentrations.
Abstract:
Indecainide, a new antiarrhythmic agent classified as type Ic was evaluated in 11 patients with heart disease who had greater than or equal to 30 ventricular premature complexes/hour, moderate-to-marked left ventricular dysfunction, and mean ejection fraction 34% +/- 8%. Patients received indecainide, 50 mg by mouth, every 6 hours and the dose was increased until greater than or equal to 80% suppression was noted, adverse effects occurred, or a maximum dose of 100 mg indecainide was given every 6 hours. Ventricular premature complexes were suppressed greater than or equal to 80% in nine patients (p less than 0.05) and ventricular tachycardia episodes were completely suppressed in five of eight patients. The effective or maximal mean daily indecainide dose was 191 +/- 32 mg; half of the responders achieved achieved efficacy at serum drug concentration greater than or equal to 600 ng/ml. Serum drug concentration was directly related to gender (r = 0.78, p less than 0.04) and inversely related to creatinine clearance (r = 0.74, p less than 0.05) and ejection fraction (r = 0.71, p less than 0.02). Indecainide prolonged mean PR and QRS intervals (p less than 0.05) but not QT or QTc. There was a linear relation between percent change in PR (r = 0.80, p less than 0.001) and QRS (r = 0.66, p less than 0.001) intervals and serum drug concentration. After starting or increasing the dose, careful observation of patients with decreased renal function or reduced ejection fraction should be exercised because they attain higher drug concentration than normal subjects.