Overview of Beta Blockers for Systolic Heart Failure: Brief Overview of Beta Blockers
In 1948, Ahlquist demonstrated that adrenergic receptors can be divided into two types: alpha and beta. A decade later, a specific inhibitor of the beta class of adrenergic receptors was identified. There are at least three subtypes of beta receptors:
- Beta 1 receptors are found primarily in heart myocytes. Blockade of beta 1 receptors slows the heart rate, reduces contractility, and delays atrioventricular (AV) con-duction.
- Beta 2 receptors are also found in heart tissue, but they are more numerous in bronchial and peripheral vascular smooth muscle. These receptors mediate broncho-dilation and vasodilation. Blockade of beta 2 receptors is what gives nonselective beta blockers their broncho-spastic potential.
- Beta 3 receptors are found in heart and adipose tissue and may serve to reduce cardiac contractility.
The recognition of the different beta receptors gave rise to the development of beta blockers that were relatively selective at one of the receptor subtypes. In addition to being classified as selective or nonselective, beta blockers are also characterized according to whether they have intrinsic sympathomimetic activity. This is the characteristic of a beta blocker that induces a slight cardiac stimulation that can be blocked by generic propranolol (e.g., Innopran, Reliant; Inderal, Wyeth).
The reduced contractility mediated by beta 1 blockade was the principal reason why beta blockers were historically considered to be contraindicated in patients with CHF. It seemed sensible to avoid anything that could further weaken an already weakened muscle. This sentiment began to change in the early 1990s as a better understanding of the role of neurohormonal systems in the pathophysiology of CHF took hold.
Beta Blockers in Systolic Dysfunction
Despite the relatively recent change in attitudes about beta-blocker usage in heart failure, the idea that beta blockade might actually benefit patients with CHF is three decades old. In 1975, Waagstein et al. reported that beta blockade improved ejection fraction and clinical status in seven patients with congestive cardiomyopathy and that withdrawal of beta-blocker therapy resulted in clinical deterioration. In the 1990s, a series of studies demonstrated the positive effects of various beta blockers on contractility and hemodynamics.
The concept that beta blockers might prolong survival in CHF patients was first reported in 1979. In the past 10 years, a number of large, well-designed studies have confirmed improvement in overall survival in patients with CHF who were treated with long-acting metoprolol, carvedilol drug (Coreg generic, GlaxoSmithKline), and bisoprolol canadian (Zebeta tablet, Duraed). Bucindolol also improves cardiovascular, but not overall, mortality in patients with CHF.
In these studies, the effects of beta blockade were additive to that of standard heart failure therapy. As a result of these accumulating data, beta blockade for symptomatic systolic dysfunction was graded a class IA recommendation in the 2001 updated American College of Cardiology/American Heart Association (ACC/AHA) guidelines for CHF.