In myocardial ischaemia and
heart failure, beta-blockers with intrinsic
sympathomimetic activity (ISA) e.g.
pindolol,
xamoterol,
bucindolol,
nebivolol, have performed poorly in reducing morbidity and mortality. In both indications beta-1 blockade is the vital active ingredient. Beta-1 blockade (
bisoprolol) is now an alternative first-line choice to Ace-inhibition in the treatment of
heart failure. The therapeutic role of beta-blockers in
hypertension is less well understood, particularly since the new recommendations in the UK from the NICE committee stating that: 1. beta-blockers are no longer preferred as a routine initial
therapy, 2. the combination with
diuretics is discouraged due to the risk of induced diabetes, and 3. in younger patients first-choice initial
therapy should be an
ACE-inhibitor. Recent data from the Framingham Heart Study and other epidemiological studies have indicated that the development of diastolic
hypertension in younger subjects is closely linked to weight-increase and an increase in peripheral resistance; such subjects have a high
adrenergic drive and cardiac output. In contrast, elderly
systolic hypertension mostly arises de novo via poor vascular compliance. Thus in younger, probably
overweight, hypertensives (including diabetics) first-line beta-blockade has performed well in preventing
myocardial infarction (a fact hidden by meta-analyses that do not take age into account). Conversely, in elderly hypertensives first-line beta-blockade (
atenolol) has performed poorly in reducing cardiovascular risk (due to partial beta-2 blockade
atenolol evokes metabolic disturbance and does not improve vascular compliance, or effectively lower central aortic pressure or reverse
left ventricular hypertrophy). Thus beta-blockers like
atenolol are ill-equipped for first-line
therapy in elderly
hypertension. Some beta-blockers, e.g.
bisoprolol (up to 10 mg/day is highly beta-1 selective) and
nebivolol (beta-2/3 intrinsic
sympathomimetic activity), do improve vascular compliance and cause no metabolic disturbance. Beta-blockers as second-line to low-dose
diuretics (which, by improving vascular compliance and increasing sympathetic nerve activity, create an optimal environment for beta-blockade) in elderly
hypertension (including diabetics) have performed well in reducing cardiovascular events (this combination has the added bonus of reducing the risk of
bone fracture by about 30%). Meta-analyses which include studies where it is unclear whether a
diuretic or beta-blocker was a first-line
therapy will dilute the benefit stemming from first-line
diuretic/second-line beta-blockade. Hypertensives (of all ages) with ischaemia are well suited to beta-blockade.