Are tolerability concerns a class effect of beta-blockers in treating patients with hypertension?

Beta-blockers (beta-blockers) have demonstrated their value across the cardiovascular disease spectrum. Beta-blockers effectively lower blood pressure in patients with hypertension and provide symptomatic or mortality benefits in patients with heart failure and in post-myocardial infarction patients. However, despite their utility, beta-blockers remain underused. There have been recent concerns that beta-blockers as a class are not as effective as once thought in uncomplicated hypertension due to a relatively weak effect on reduction of stroke and the absence of an effect on coronary heart disease when compared with placebo or no treatment. Underuse can, in part, be related to tolerability concerns. Beta-blockers have been traditionally associated with side effects including depression, fatigue, sexual dysfunction, and cold extremities, which limit their acceptance by patients and physicians and may lead to discontinuation of therapy. Because of inherent heterogeneity of the beta-blocker class in terms of adrenergic receptor selectivity, intrinsic sympathomimetic activity, and vasodilatory activity, these agents vary in tolerability profile. Recently, more attention has been focused on the third-generation vasodilatory beta-blockers (ie, carvedilol, labetalol, and nebivolol), with the recognition that these agents may diverge in meaningful ways from the traditional beta-blockers. By examining the differences among members of the beta-blocker class, it may be possible to determine whether and which tolerability issues are indeed a class effect of beta-blockers or whether these agents should be evaluated on a case-by-case basis.