Effect of indecainide in patients with left ventricular dysfunction

Indecainide, a new antiarrhythmic agent classified as type Ic was evaluated in 11 patients with heart disease who had ≥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 ≥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 ≥80% in nine patients ( p < 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 efficacy at serum drug concentration ≥600 ng/ml. Serum drug concentration was directly related to gender ( r = 0.78, p < 0.04) and inversely related to creatinine clearance ( r = 0.74, p < 0.05) and ejection fraction ( r = 0.71, p < 0.02). Indecainide prolonged mean PR and QRS intervals ( p < 0.05) but not QT or QTc. There was a linear relation between percent change in PR ( r =0.80, p <0.001) and QRS ( r = 0.66, p <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. Clinical Pharmacology and Therapeutics (1990) 48, 582–589; doi: 10.1038/clpt.1990.195