A Review of Why and How We May Use β-Blockers in Congestive Heart Failure: β-Blockers and ACE Inhibitors
β-Blockers and ACE Inhibitors
Angiotensin II causes an increase in adrenergic neurotransmitter activity, and ACE inhibitors can decrease norepinephrine in venous blood and are therefore said to be antiadrenergic and like β-blockers, can increase β-receptor density.
During the acute stages of CHF, an increase in the renin-angiotensin system is necessary to maintain pressure. However, chronically high angiotensin levels increase afterload, which depresses myocardial function. Stimulation can stimulate the renin-angiotensin system, and β-blockers can suppress renin output. The decrease in angiotensin II will decrease vasoconstriction, thereby attenuating any elevation in afterload. Therapy with β-blockers plus ACE inhibitors inhibits the renin-angiotensin system by two different pathways and suggests that they would have an additive benefit in CHF.
In 1995, a report on enalapril and β-blockers was published. A group of 6,797 patients with ejection fractions of <0.35 while receiving enalapril were pitted against a group in whom β-blockers were added to the enalapril. There was an additional decrease in mortality and hospitalization in those with the added β-blockers. However, it is possible that the patients who tolerated β-blockers may have had less CHF to begin with. diabetes amaryl
It is questionable whether β-blockers with intrinsic sympathomimetic activity should be used since they can increase pulmonary and vascular resistance and therefore increase afterload.
The nonselective β-blockers bucindolol and carvedilol have both β-blocking and very mild vasodilator effects, and therefore are usually better tolerated when beginning treatment except for a greater tendency to postural hypotension than with metoprolol. They manifest a dose-related improvement in cardiac output and ejection fraction.
It may be an advantage to use a drug like carvedilol that has no upregulation effect because although the absence of a strong inotropic effect at high workloads may limit exercise capacity, it may decrease the risk of sudden death by preventing plaque rupture in patients with ischemic heart disease. Carvedilol has the added advantage over metoprolol in that it has antioxidant and antiproliferative properties. Gilbert and colleagues,65 in 1996, reported on a comparison of two concurrent placebo-controlled trials with carvedilol or metoprolol. They found that carvedilol in comparison with metoprolol showed greater improvement on function and ejection fraction and less coronary norepinephrine.