Comparative efficacy and safety of oral tocainide and quinidine for benign and potentially lethal ventricular arrhythmias.

The antiarrhythmic efficacy and safety of oral tocainide hydrochloride and quinidine sulfate were compared in a double-blind, 3-center, parallel trial involving 133 patients with benign and potentially lethal ventricular arrhythmias. Baseline demographic, etiologic, functional and ventricular arrhythmia data were not significantly different between the 2 groups. Two weeks of an initial placebo period were followed by 8 weeks of active drug treatment, concluding with 4 weeks of washout. Frequent 24-hour ambulatory electrocardiographic monitoring was used to judge efficacy. Ten of 27 patients (37%) receiving tocainide and 12 of 24 patients (50%) receiving quinidine had a 75% reduction with drug treatment compared with the initial placebo period (p greater than 0.25). Total abolition of ventricular tachycardia occurred in 6 of 16 patients (37%) receiving tocainide and 6 of 13 patients (43%) receiving quinidine (p greater than 0.25). Conditions that required discontinuation of therapy occurred in 18 of 67 patients (27%) receiving tocainide and 16 of 66 (24%) receiving quinidine (difference not significant). More patients had dizziness during tocainide treatment and diarrhea during quinidine treatment. Quinidine caused a prolongation in the QT interval (0.03 second); tocainide caused a slight reduction (0.01 second). No important changes in vital signs or laboratory measurements were observed in left ventricular ejection fraction when measured. Thus, tocainide, the new oral analog of lidocaine, appears to be as safe as quinidine but is slightly less effective in suppressing ventricular arrhythmias.

Valsartan, a new angiotensin II receptor antagonist: a double-blind study comparing the incidence of cough with lisinopril and hydrochlorothiazide.

The present study compares the occurrence of a dry, persistent cough with doses of 80 mg of valsartan, 10 mg of lisinopril, or 25 mg of hydrochlorothiazide in patients with a history of angiotensin-converting enzyme inhibitor-induced cough. This was a randomized, double-blind, active-controlled, parallel group, multicenter trial involving 129 adult outpatients with essential hypertension. After confirmation of angiotensin-converting enzyme inhibitor-induced cough during a 2 to 4 week challenge with lisinopril (followed by a washout period of 2 weeks), patients were randomized to receive 6 weeks of double-blind treatment once daily with 80 mg valsartan, 10 mg lisinopril, or 25 mg hydrochlorothiazide. Assessments were made at baseline and after 3 and 6 weeks of treatment. Comparability of response to treatment was assessed by mean sitting diastolic and systolic blood pressure at the end of treatment. The occurrence of a dry, persistent cough was significantly less (P < 0.001) at 3 and 6 weeks with valsartan (19.5%) than with lisinopril (68.9%), with no significant difference between valsartan and hydrochlorothiazide (19.0%). There were no statistically significant differences in reduction of blood pressure among the three treatment groups. The overall incidence of adverse experiences, whether or not treatment-related, was highest for lisinopril (86.7%) compared with valsartan (57.1%), and hydrochlorothiazide (61.9%). A dry cough in the lisinopril group accounted for this difference. There were no clinically significant changes in physical signs or in results of clinical laboratory evaluations during double-blind treatment, except for from metabolic changes in 3 patients receiving hydrochlorothiazide. In hypertensive patients with a history of angiotensin-converting enzyme inhibitor-induced cough, a single daily dose of 80 mg of valsartan produced therapeutic efficacy comparable to lisinopril but with significantly less cough.

A randomized, double-blind, parallel group comparison of disopyramide phosphate and quinidine in patients with cardiac arrhythmias.

This report summarizes the results of a randomized, double-blind, parallel group, multicenter study which compared the antiarrhythmic activity and safety of oral disopyramide phosphate and oral quinidine sulfate. A total of 124 outpatients, whose pretreatment rates of ventricular and/or supraventricular arrhythmias were documented by ambulatory ECG recordings, were randomly assigned to receive either oral disopyramide or oral quinidine for the eight-week course of the study. Every two weeks, ten-hour ambulatory ECG recordings were obtained from each patient and blood was drawn to determine serum concentrations of assigned drug.

Antihypertensive efficacy of sustained-release verapamil.

The antihypertensive effects of immediate-release (IR) verapamil were compared with those of sustained-release (SR) verapamil in 58 patients. After an open-label (IR verapamil) study, patients were randomized into a double-blind study to continue receiving the same dose of IR verapamil three times daily or an equivalent dose of SR verapamil (240 to 480 mg) once daily. Blood pressure decreased from 149/98 to 139/90 mmHg (p less than 0.01) with IR verapamil and from 150/98 to 136/88 mmHg (p less than 0.01) with SR verapamil. Ambulatory blood pressure monitoring showed a similar response for the two formulations. Diastolic pressure was less than 90 mmHg in approximately 67% of the IR verapamil group and 61% of the SR verapamil group. Mean trough plasma concentrations of verapamil were 70 and 59 ng/ml at 2 and 4 weeks, respectively, after treatment with IR verapamil; the corresponding values were 70 and 94 ng/ml for the SR verapamil group. SR verapamil administered once daily is an effective antihypertensive medication in a selected group of patients and could afford better compliance.