Beta-blockers and heart failure

Abstract

The life-time risk of developing HF is about 20% (40% if hypertension present). With increasing longevity in the developed world the burden of HF (hospitalisation) is set to increase over the next 10-20 years. CAD and hypertension are the two main causes of HF; CAD (and obesity) in the case of systolic HF and hypertension in the case of diastolic HF (mainly in the elderly). BB have become the corner-stone (alongside ACE-inhibitors) in the treatment of systolic HF. Bisoprolol, metoprolol and carvedilol (on an ACE-inhibitor background) have reduced all-cause death by 34-5%. The presence of intrinsic sympathomemetic activity (xamoterol, bucindolol, nebivolol) diminishes efficacy in the treatment of systolic HF. First-line bisoprolol has proved "non-inferior" to first-line enalapril in reducing all-cause death and is probably superior in reducing sudden death. The main mode of action of BB in treating systolic HF is inhibition of chronic beta-1 stimulation-induced myocardial apoptosis/necrosis/inflammation. The combination of pure beta-1 blockade (low-dose bisoprolol) and pure beta-2 blockade (clenbuterol) may prove invaluable in the treatment of end-stage systolic HF (thus avoiding cardiac transplantation). The appropriate treatment of diastolic HF has yet to be determined. Beta-blockade is effective in the prevention of HF i) in the post-MI period and ii) as first-line agents in the treatment of young/middle-aged hypertension and as second-line agents (to first-line diuretics) in the treatment of elderly systolic hypertension. BB are highly effective in reversing LVH in young/middle-aged hypertensives (LVH pre-disposes to HF in young/middle-aged hypertension) and are (bisoprolol) at least as good as ACE-inhibitors. Choice of BB is important as benefit is not a class-effect. ISA (xamoterol, bucindolol, nebivolol) markedly diminishes efficacy. The choice is between bisoprolol, metoprolol succinate and carvedilol for optimal efficacy. Adverse reactions are associated, mainly, with beta-2 blockade and alpha-blockade. Thus non-selective (e.g. propranolol) or modestly beta-1 selective (e.g. metoprolol, atenolol) are associated with metabolic disturbance, bronchospasm, epinephrine/hypertensive interaction (with cigarette-smoking or insulin-induced hypoglycaemia), while the possession of alpha-blocking activity (e.g. carvedilol) is associated with dizziness and postural hypotension. The possession of beta-2 blockade, particularly if combined with alpha-blockade, is associated with an increased occurrence of sexual dysfunction. Lipophilic BB like propranolol and metoprolol appear in high concentrations in human brain tissue and are associated with side-effects such as insomnia, dreams and nightmares.