Lipophilic versus hydrophilic β1 blockers and the cardiac sympatho-vagal balance during stress and daily activity in patients after acute myocardial infarction

Objective To compare the effects of a lipophilic and a hydrophilic β1 blocker on cardiac sympatho-vagal balance during daytime activity and stress in patients four to six weeks after myocardial infarction. Design Randomised, double blind, crossover study comparing the effect of atenolol (50 mg once daily) with metoprolol CR (100 mg once daily) with treatment periods of four weeks. Setting Large teaching hospital. Patients 50 patients (45 male, 5 female, age range 40 to 75 years), four to six weeks after an acute myocardial infarction. Methods At the end of each treatment period the 24 hour heart rate variability, heart rate variability power spectra during head up tilt and mental stress, baroreflex sensitivity, and exercise performance were evaluated. Results During daytime activity and during orthostatic and mental stress, both heart rate and the ratio between the low and high frequency spectral components of the heart rate variability were significantly lower with atenolol. Conversely, there was no difference between treatments in baroreflex sensitivity and resting plasma catecholamines. Exercise duration and peak oxygen consumption did not differ between treatments, but the heart rate during submaximal and peak exercise was significantly lower with atenolol. Conclusions At the doses used in this study, atenolol achieved greater β1 adrenergic blockade than metoprolol CR and this was associated with significant inhibition of vagal withdrawal during stress. This suggests that peripheral blockade of β1 adrenergic receptors may be more important than central blockade in preventing stress induced vagal withdrawal in patients after myocardial infarction.