Comparison of the Subacute Hemodynamic Effects of Atenolol, Propranolol, Pindolol, and Nebivolol

Abstract

In an observer-blind four-way crossover study, 7 healthy volunteers received in random sequence, one month apart, atenolol 100 mg od, propranolol (slow release) 160 mg od, pindolol 5 mg tid, and nebivolol 5 mg od for a period of seven days, followed by a single-blind placebo washout period of seven days. The decrease of peak exercise heart rate and systolic blood pressure was significant (p = 0.02) and comparable for the four drugs studied and varied between 15% and 23% for heart rate and between 15% and 20% for systolic blood pressure. Although no statistically significant difference was observed among the four drug regimens, the decrease of peak exercise heart rate was less pronounced with nebivolol than with the three reference beta-blocking agents. The ratio of the preejection period (PEPc) to the left ventricular ejection time (LVETc), an indirect measure of left ventricular performance, tended to increase with atenolol and propranolol and remained unchanged with pindolol. PEPc/LVETc progressively and significantly improved with nebivolol from a control value of 0.37 +/- 0.012 to 0.31 +/- 0.009 (p = 0.03) after seven days of treatment, owing to a decrease in PEPc and an increase in LVETc, suggestive of a combined effect both on preload and afterload. Postexercise LVETc, an index of the intrinsic positive inotropy of exercise, was significantly suppressed by atenolol, propranolol, and pindolol, but not during treating with nebivolol. These data suggest that nebivolol is a beta 1-selective adrenergic antagonist with an unusual hemodynamic profile, probably improving left ventricular compliance.

Integrated effects of the vasodilating beta-blocker nebivolol on exercise performance, energy metabolism, cardiovascular and neurohormonal parameters in physically active patients with arterial hypertension

“…The pharmacological profile is characterised by the significant antihypertensive effects as well as a lowering of cardiac pre-and after-load. 24 Up to now, however, there is still a lack of information about possible interactions of nebivolol with concomitant physical activity in patients with essential hypertension (EH). In this context, the effects of nebivolol on parameters of physical performance in connection with systemic haemodynamics, energy metabolism, lactate levels, oxygen uptake and subjective feeling of physical stress are of fundamental interest.…”

Effect of nebivolol on left ventricular function in patients with chronic heart failure: a pilot study

“…However, the decrease in heart rate was not as pronounced as with atenolol [14,15]. During exercise testing the maximal heart rate was also reduced but the maximal duration of the bicycle test and maximal work load were not altered in contrast to propranolol, atenolol and pindolol [16,17]. Wisenbaugh et al [18] have shown that nebivolol significantly reduced left ventricular end‐diastolic pressure as a result of the improvement in systolic performance and exercise tolerance remained constant.…”

Pharmacological Mechanisms of Clinically Favorable Properties of a Selective β1‐Adrenoceptor Antagonist, Nebivolol

“…During exercise, the rise in systolic blood pressure and heart rate is less depressed with nebivolol than with atenolol (53). Postexercise left ventricular ejection time, an index of the intrinsic positive inotropy of exercise, was significantly suppressed by atenolol, propranolol or pindolol, but not by nebivolol (19).…”

“…Patients receiving â-adrenoceptor antagonists for the treatment of hypertension frequently complain of impaired exercise tolerance. In numerous placebo-controlled crossover studies it was demonstrated, that therapy with nebivolol does not lead to significant reduction of exercise tolerance (19,46,53). In contrast to atenolol, nebivolol did not decrease maximal and endurance exercise capacity, and did not increase perceived exertion.…”