Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies
Drs Law, Morris and Wald (1) are to be congratulated in concluding
that beta-blockers do have an important role to play in the treatment of
hypertension: thus strongly disagreeing with the UK-NICE guidelines (2)
which removed beta-blockers as preferred choices in the treatment of
hypertension.
Indeed the beta-blocker benefit in most hypertensives, i.e. the 70-75% of
non-smokers, is under-stated. In non-smoking/middle-aged males the
frequency of myocardial infarction (main cause of death) was reduced by 33
-50% by non-selective oxprenolol vs diuretic (IPPPSH), non-selective
propranolol vs placebo vs diuretic (MRC mild hypertensive trial)(3) and
moderately beta-1 selective metoprolol vs diuretic (MAPHY). By contrast,
in the 25-30% smokers the above benefits were abolished (also, in the MRC
mild hypertensive trial(3) the 54% reduction in stroke-frequency by
propranolol in non-smokers was converted to a 21% increase in smokers).
Even in the elderly (MRC-elderly study) the non-significant small
benefits in reducing cardiovascular events in non-smokers by first-line
moderately beta-1 selective atenolol (vs placebo) were converted to
potential harm in the smokers (approximate 40% increase).
The likely mechanism of the beta-blocker-smoking- interaction is linked to
the smoking-induced increase (2-3 fold) in adrenaline secretion, lasting
at least 30 minutes (4). Adrenaline stimulates beta-1, beta-2 and alpha -
receptors, so that in the presence of beta-1 plus beta-2 blockade the
unbridled alpha-constriction results in a marked (with non-selective beta-
blockers) and moderate (with moderately beta-1 selective beta-blockers)
hypertensive response: not observed with high beta-1 selectivity
(bisoprolol) (5).
The conclusion that the cardiovascular -benefits associated with all anti-
hypertensive agents is purely due to the fall in blood-pressure may be
incorrect, as in the MRC mild hypertensive study (3) blood-pressure
control was best with diuretics (vs propranolol) yet only propranolol (in
the majority ie non-smokers) effected a significant 33% fall in the
frequency of myocardial infarction vs zero-effect of diuretics.
References
1. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in
the prevention of cardiovascular disease: meta-analysis of 147 randomised
trials in the context of expectations from prospective epidemiological
studies. BMJ 2009;338:b1665 doi: 10.1136/bmj. b 1665.
2. NICE clinical guidelines 34. Hypertension management of hypertension
in primary care. WWW.nice.org.uk, ISBN 1-84629-222-0. June 2006-08-01.
3. Medical Research Council Working Party. MRC Trial of treatment of
mild hypertension: principal results. BMJ 1985;291:97-104.
4. Cryer PE, Haymond MW, Satiago JV, Shar SP. Norepinephrine and
epinephrine release and adrenergic mediation of smoking-associated
haemodynamic and metabolic events. N Engl J Med 1976;295:573-7.
5. Tarnow J, Muller RK> Cardiovascular effects of low-dose adrenaline
infusions in relation to the extent of preoperative beta-adrenoceptor
blockade. Anaesthesiology 1991;74:1035-43.
Rapid Response:
Beta-blockers in the treatment of hypertension
Drs Law, Morris and Wald (1) are to be congratulated in concluding
that beta-blockers do have an important role to play in the treatment of
hypertension: thus strongly disagreeing with the UK-NICE guidelines (2)
which removed beta-blockers as preferred choices in the treatment of
hypertension.
Indeed the beta-blocker benefit in most hypertensives, i.e. the 70-75% of
non-smokers, is under-stated. In non-smoking/middle-aged males the
frequency of myocardial infarction (main cause of death) was reduced by 33
-50% by non-selective oxprenolol vs diuretic (IPPPSH), non-selective
propranolol vs placebo vs diuretic (MRC mild hypertensive trial)(3) and
moderately beta-1 selective metoprolol vs diuretic (MAPHY). By contrast,
in the 25-30% smokers the above benefits were abolished (also, in the MRC
mild hypertensive trial(3) the 54% reduction in stroke-frequency by
propranolol in non-smokers was converted to a 21% increase in smokers).
Even in the elderly (MRC-elderly study) the non-significant small
benefits in reducing cardiovascular events in non-smokers by first-line
moderately beta-1 selective atenolol (vs placebo) were converted to
potential harm in the smokers (approximate 40% increase).
The likely mechanism of the beta-blocker-smoking- interaction is linked to
the smoking-induced increase (2-3 fold) in adrenaline secretion, lasting
at least 30 minutes (4). Adrenaline stimulates beta-1, beta-2 and alpha -
receptors, so that in the presence of beta-1 plus beta-2 blockade the
unbridled alpha-constriction results in a marked (with non-selective beta-
blockers) and moderate (with moderately beta-1 selective beta-blockers)
hypertensive response: not observed with high beta-1 selectivity
(bisoprolol) (5).
The conclusion that the cardiovascular -benefits associated with all anti-
hypertensive agents is purely due to the fall in blood-pressure may be
incorrect, as in the MRC mild hypertensive study (3) blood-pressure
control was best with diuretics (vs propranolol) yet only propranolol (in
the majority ie non-smokers) effected a significant 33% fall in the
frequency of myocardial infarction vs zero-effect of diuretics.
References
1. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in
the prevention of cardiovascular disease: meta-analysis of 147 randomised
trials in the context of expectations from prospective epidemiological
studies. BMJ 2009;338:b1665 doi: 10.1136/bmj. b 1665.
2. NICE clinical guidelines 34. Hypertension management of hypertension
in primary care. WWW.nice.org.uk, ISBN 1-84629-222-0. June 2006-08-01.
3. Medical Research Council Working Party. MRC Trial of treatment of
mild hypertension: principal results. BMJ 1985;291:97-104.
4. Cryer PE, Haymond MW, Satiago JV, Shar SP. Norepinephrine and
epinephrine release and adrenergic mediation of smoking-associated
haemodynamic and metabolic events. N Engl J Med 1976;295:573-7.
5. Tarnow J, Muller RK> Cardiovascular effects of low-dose adrenaline
infusions in relation to the extent of preoperative beta-adrenoceptor
blockade. Anaesthesiology 1991;74:1035-43.
Competing interests:
None declared
Competing interests: No competing interests