Effects of nadolol on the spontaneous and exercise-provoked heart rate of patients with chronic atrial fibrillation receiving stable dosages of digoxin.

Nadolol, a long-acting beta-adrenergic-blocking agent, was evaluated in 20 patients with chronic atrial fibrillation by means of a randomized, double-blind, crossover study. Patients were required either to demonstrate resting heart rates in excess of 80 bpm or to show a rate of 120 bpm or an increment of greater than 50 bpm during mild treadmill exercise provocation (3 minutes, 1.75 mph, 10% grade). With placebo the group averaged a heart rate of 92 +/- 19 bpm, determined by 24 hours of ambulatory ECG recordings; this rate was significantly reduced to 73 +/- 16 bpm (p less than 0.001) with nadolol (mean dosage, 87 +/- 43 mg/day). During standardized exercise testing, heart rates increased to 153 +/- 26 bpm with placebo and to 111 +/- 24 bpm with nadolol (p less than 0.001), representing 65% and 52% increments, respectively. Digoxin blood levels averaged 0.8 +/- 0.5 ng/ml with placebo and were similar with nadolol (0.9 +/- 0.4; p = NS). Total exercise time on a modified Bruce treadmill protocol was 466 +/- 143 seconds with placebo and was significantly decreased by nadolol (380 +/- 143; p less than 0.01). During initial dose titration with nadolol, one patient was dropped from study for intolerable fatigue and one for worsened claudication. No patients were dropped from the double-blind treatment periods, although two patients receiving nadolol and one patient receiving placebo complained of moderate fatigue. We conclude that nadolol is a safe and effective agent for the control of spontaneous and exercise-provoked heart rates in patients with chronic atrial fibrillation who were already receiving digoxin treatment.

Bepridil for chronic stable angina pectoris: results of a prospective multicenter, placebo-controlled, dose-ranging study in 77 patients.

Bepridil, a new calcium-channel blocking agent with an extended plasma elimination half-life of greater than 50 hours, was compared to placebo in 77 patients with confirmed coronary artery disease and chronic stable angina pectoris. The effects of bepridil were compared with those of placebo on angina frequency, nitroglycerin tablet use, the resting ECG and hemodynamics at rest and maximal exercise using a study design comprising 5 sequential 2-week single-blind treatment phases. After 2 weeks of placebo (phase 1), bepridil was given for 3 phases (2, 3 and 4) at total daily dosages of 200, 300 and 400 mg, respectively; the study was completed after a final reintroduction of placebo (phase 5). Within each phase once- and twice-daily regimens of bepridil were randomly compared. Bepridil (300 mg/day) reduced anginal frequency 68%, from 8.5 +/- 1.1 (standard error of the mean) to 2.7 +/- 0.7 attacks/week and nitroglycerin tablet use 76% (p less than 0.001). Bepridil improved exercise duration 26%, from 6.9 +/- 0.4 to 8.7 +/- 0.5 minutes (p less than 0.001) and exercise work 52%, from 2.7 +/- 0.3 to 4.1 +/- 0.4 kpm X 10(-3) (p less than 0.001) on a standardized treadmill protocol. Resting and peak exercise heart rate and blood pressure were unaffected by bepridil. The antianginal effects were similar with either once- or twice-daily treatment schedules. Minor side effects of nausea, epigastric discomfort and tremor were infrequent and there were no major side effects. The results of this large but preliminary, single-blind and short-term study suggest that bepridil is an effective and well tolerated antianginal agent when administered once daily.

Creatine kinase MB isoenzyme in dermatomyositis: a noncardiac source.

Three patients with polymyositis had elevated serum levels of creatine kinase MB isoenzyme. The presence of this isoenzyme is used extensively to diagnose myocardial infarction, but the isoenzyme is also found in sera of patients with primary muscular and neuromuscular disorders. We studied cardiac function in two of our patients with electrocardiograms, technetium stannous pyrophosphate scanning, and technetium 99m-labeled erythrocyte gated blood pool imaging and in the third patient by postmortem examination. There was no evidence of myocardial involvement to account for the high serum levels of isoenzyme. Creatine kinase MB in the sera of patients with polymyositis does not necessarily indicate myocardial necrosis.