Comparison of captopril and ibopamine in mild to moderate heart failure.

OBJECTIVE: To determine the effects of ibopamine 100 mg three times daily compared with captopril 25 mg three times daily on exercise capacity in patients with chronic heart failure. DESIGN: A randomised, double blind, parallel group comparison of the addition of ibopamine versus captopril during a period of 24 weeks. SETTING: 26 outpatient cardiology clinics in seven European countries. PATIENTS: 266 patients, with mild to moderate chronic heart failure (New York Heart Association (NYHA) functional class II, 81% and III, 19%) and evidence of an enlarged left ventricle. Patients received concomitant treatment with diuretics and/or digitalis. MAIN OUTCOME MEASURE: Exercise duration after 24 weeks of treatment, compared with baseline. RESULTS: Mean (SD) ejection fraction was 29 (8)% and the baseline exercise duration in the captopril and ibopamine groups 665 (160) and 675 (174) seconds, respectively. At the end of the study, exercise duration had improved in both groups, by 29 seconds in the ibopamine group (P < 0.01), and by 24 seconds in the captopril group (P < 0.05). There was no difference between groups (P = 0.69, 95% confidence interval -22 to 33). NYHA class, signs and symptoms score, and dyspnoea and fatigue index improved equally in both groups. The total number of adverse events was the same in both treatment groups, but gastrointestinal complaints occurred more often in the ibopamine group. The number of patients with premature withdrawals was no different. CONCLUSIONS: No difference was detected between the effect of captopril and ibopamine on exercise time in patients with mild to moderate heart failure during a treatment period of 24 weeks.

Double-blind placebo-controlled study of ibopamine and digoxin in patients with mild to moderate heart failure: results of the Dutch Ibopamine Multicenter Trial (DIMT).

OBJECTIVES: This study was conducted to determine the efficacy and safety of long-term treatment with the orally active dopamine agonist ibopamine in patients with mild to moderate chronic congestive heart failure and to compare the results with those of treatment with digoxin and placebo. BACKGROUND: Ibopamine and digoxin are drugs that exert hemodynamic and neurohumoral effects. Because there is accumulating evidence that progression of disease in chronic heart failure is related not only to hemodynamic but also to neurohumoral factors, both drugs might be expected to have a favorable long-term effect. METHODS: We studied 161 patients with mild to moderate chronic heart failure (80% in New York Heart Association functional class II and 20% in class III), who were treated with ibopamine (n = 53), digoxin (n = 55) or placebo (n = 53) for 6 months. Background therapy consisted of furosemide (0 to 80 mg); all other drugs for heart failure were excluded. Clinical assessments were made at baseline and after 1, 3 and 6 months. RESULTS: Of the 161 patients, 128 (80%) completed the study. Compared with placebo, digoxin but not ibopamine significantly increased exercise time after 6 months (p = 0.008 by intention to treat analysis). Ibopamine was only effective in patients with relatively preserved left ventricular function, as it significantly increased exercise time in this subgroup (for patients with a left ventricular ejection fraction > 0.30; p = 0.018 vs. placebo). No patient receiving digoxin withdrew from the study because of progression of heart failure, compared with six patients receiving ibopamine and two receiving placebo. At 6 months, plasma norepinephrine was decreased with digoxin and ibopamine therapy (-106 and -13 pg/ml, respectively) but increased with placebo administration (+62 pg/ml) (both p < 0.05 vs. placebo). Plasma aldosterone was unaffected, but renin was decreased by both agents after 6 months (p < 0.05 vs. placebo). Total mortality and ambulatory arrhythmias were not significantly affected by the two drugs. CONCLUSIONS: Ibopamine and digoxin both inhibit neurohumoral activation in patients with mild to moderate chronic heart failure. However, the clinical effects of these drugs are different and appear to be related to the degree of left ventricular dysfunction.

Atrioventricular conduction disturbance as an early feature of Reiter's syndrome.

Atrioventricular (A-V) conduction disturbances in Reiter's syndrome are usually described in longstanding disease. This report deals with two male patients with Reiter's syndrome who developed an A-V block early in the course of the disease. One of these patients developed a second degree A-V block, Wenckebach type, which has not been described before at an early stage of this syndrome.

Effect of procainamide, propranolol and verapamil on mechanism of tachycardia in patients with chronic recurrent ventricular tachycardia.

The effect of short-term intravenous administration of procainamide (12 patients), propranolol (4 patients) and verapamil (4 patients) was studied in 12 patients with chronic recurrent sustained ventricular tachycardia. In all patients tachycardia could reproducibly be initiated and terminated with programmed electrical stimulation of the heart. Procainamide (1) lengthened the effective refractory period of the right ventricle, (2) affected the tachycardia zone, (3) reduced ventricular rate during tachycardia, and (4) lengthened the interval between the tachycardia-initiating premature ventricular beat and the first QRS complex of tachycardia. No effect on the refractory period of the right ventricle or the mechanism of tachycardia was seen after administration of propranolol or verapamil. Apart from their therapeutic implications these data suggest that it may be possible to use drugs to study mechanisms of ventricular tachycardia in the human heart.

Effect of amiodarone in the Wolff-Parkinson-White syndrome.

The effect of amiodarone in the Wolff-Parkinson-White syndrome was studied with programmed electrical stimulation of the heart in 15 patients. All 15 patients had circus movement tachycardias; 7 also had atrial fibrillation. Programmed electrical stimulation was performed before and after 14 days of oral administration of amiodarone. The effective refractory period of the accessory pathway lengthened in an atrioventricular direction in all patients and in a ventriculoatrial direction in eight patients. The effective refractory period of the atrium and ventricle lengthened in 14 and 12 patients, respectively. After administration of amiodarone, circus movement tachycardia could no longer be initiated in five patients. The zone of tachycardia narrowed in four patients, did not change in two and increased in seven. The effect of amiodarone on initiation of circus movement tachycardia could be related to differences in effect of the drug and in the mechanism of tachycardia in individual patients. In all patients in whom tachycardias could still be initiated after treatment with amiodarone the heart rate during tachycardia was slower than before treatment. This slowing was caused by a decrease in conduction velocity of the circulatory wave in different parts of the tachycardia circuit. The effect of amiodarone in prolonging the refractory period of the accessory pathway makes this drug especially useful in patients with the Wolff-Parkinson-White syndrome and atrial fibrillation.