Nice guidance and beta blockers
In the summary NICE guidance on the management of hypertension (1) the
advice on the more regular use of home or ambulatory blood pressure
monitoring (to avoid "white-coat effect" seen in the clinic) was
particularly welcome. However their guidance on the first-line treatment
of hypertensives under the age of 55 years, with either an ACE inhibitor
or angiotensin receptor blocker (ARB), with no mention of beta-blockade,
is particularly hard to understand or accept.
There has been only one randomised, hard-endpoint comparison between
ACE-inhibitors and beta-blockers and that is the UKPDS study in middle-
aged, obese hypertensives with type-2 diabetes (2). After 9-10 years
follow-up the trends (vs less tight control of blood pressure) in the
reduction of the 7 primary endpoints (plus the important secondary
endpoint of heart failure) all favoured the beta-blocker atenolol over the
ACE inhibitor captopril. Clearly the atenolol-induced increase in HbA1-c
over the first 4 years was of no clinical import. Significantly, after 20
years follow-up (patients discharged to primary care at 10 years), the
trends noted at 10 years follow-up favouring those randomised to atenolol
for the reduction of myocardial infarction, peripheral vascular disease
and microvascular disease persisted, and in the case of all-cause death
strengthened to a significant 23% reduction (3). So how could an ACE
inhibitor be favoured over a beta-blocker? Is a brief increase in HbA1-c
(plus cost implications) to be considered more important than a life-
saving quality? : surely not. Besides, the tendency for non-selective and
moderately selective beta-blockers to induce metabolic disturbance can be
avoided by the use of a highly beta-1 selective agent e.g. bisoprolol (4).
Not only does bisoprolol avoid metabolic disturbance but is also the most
effective way to lower blood pressure in young-middle-aged hypertensives
The apparent disappointing results of other randomised, controlled,
hard-endpoint beta-blocker studies in middle-aged hypertensives i.e. MRC
mild hypertension (non-selective propranolol), IPPPSH (non-selective
oxprenolol) and MAPHY (moderately beta-1 selective metoprolol), was due to
an important (often unrecognised) smoking-interaction (4). In those 3
studies, in the approximate 70% non-smoking population, the beta-blocker
reduced the risk myocardial infarction (number 1 killer, being about 3
times more common than stroke) by about 35-50% vs placebo or diuretic (4).
This benefit was totally cancelled out in the smokers due to the marked
hypertensive reaction occurring with non-selective or poorly selective
beta-blockers in the presence of smoking-induced increases in adrenaline
(4). Again this dangerous beta-blocker/smoking/adrenaline interaction can
be avoided by high beta-1 selectivity i.e. bisoprolol (4).
The recommendation of an ARB as an alternative to ACE inhibitor for
the treatment of hypertensives under the age of 55 years is particularly
worrying, in view of the possibility that ARBs may increase the risk of
myocardial infarction (6). This concern was underlined by the results of a
recent randomised, placebo-controlled study in over 4000 middle-aged type-
2 diabetics with pre-hypertension (7). The number of deaths from
cardiovascular causes was higher in the ARB (olmesartan) group than in the
placebo group (13 vs 3, p = 0.01), owing primarily to more cases of fatal
myocardial infarction (5 vs 0) and sudden cardiac deaths (7 v 1) in the
Is it too late for the NICE guidance group to modify their
1 Krause T, Lovibond K, Caufield M, McCormack T, Williams B. Managment of
hypertension: summary of NICE guidance. BMJ 2011;343: d 4891.
2 UK Prospective Diabetes Study Group. Efficacy of atenolol and captopril
in reducing risk of macrovascular and microvascular complications in type
2 diabetes: UKPDS 39. BMJ 1998;317:713-9.
3 Holman RR, Paul SK, Bethel MA, Neil HA, Matthews DR. Long-term follow-
up after tight control of blood pressure in type-2 diabetes. N Eng JM
4 Cruickshank JM. The modern role of beta-blockers in cardiovascular
medicine. Peoples Medical Publishing House, USA Shelton, Connecticut,
5 Deary AJ, Schumann AL, Marfet H, Haydock S, Foo RS-Y, Brown MJ. Double
blind, placebo-controlled crossover comparison of 5 classes of
antihypertensive drugs. J Hypertens 2002;20:771-7.
6 Strauss MH, Hall A. Renin-angiotensin system and cardiovascular risk.
7 Haller H, Sadayoshi I, Izzo JL, Januszewicz A, Katayama S, Menne J
etal. Olmesartan for the delay or prevention of microalbuminuria in type-
2 diabetes. N Engl J Med 2011;364:907-17.
Competing interests: No competing interests