CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 3, April 2012
172
AFRICA
South African Hypertension Society 2012 congress report
Optimal combination therapy for hypertension
Prof Neil Poulter
Hypertension is currently the single
biggest cause of death globally. In
2000, there were a staggering 1 billion
hypertensive individuals worldwide and
this is predicted to increase to 1.56 billion
by 2025.
An increasing prevalence of
hypertension is being witnessed in all
nations, with numerous risk factors
contributing to this upward trend.
These sobering statistics formed the
introduction to this presentation, which
examined optimal combination therapy
for hypertension by investigating a variety
of guidelines and recent trial data.
Prof Neil Poulter, Imperial College,
London, listed among the risk factors for
hypertension an increasing life expectancy
in many nations (hence a larger number of
elderly) and a trend towards a sedentary
lifestyle. Other factors include decreased
fresh fruit and vegetable consumption,
an increase in obesity and smoking, and
an increased intake of saturated fats, salt
and alcohol.
Hypertension guidelines for
first-line therapy
Prof Poulter emphasised, ‘It is important
to get treatment of hypertension right, in
order to prevent cardiovascular disease
down the line.’ He then compared the
different guidelines: JNC7, ESH-ESC,
WHO-ISH and BHS/NICE2006. They
were found to have differing opinions on
optimal first-line therapy.
BHS states that monotherapy is
usually inadequate therapy. Both JNC7
and ESH-ESC recommend two drug
combinations (dual therapy), and the
2009 ESH-ESC guidelines selected five
preferred combinations:
•
angiotensin converting enzyme inhibi-
tor (ACE) + diuretic
•
angiotensin receptor blocker (ARB) +
diuretic
•
calcium channel blocker (CCB) +
diuretic
•
ACE + CCB
•
ARB + CCB (no trial evidence).
‘The advantages of dual therapy in
reduction of stroke and coronary risk
is evident in more than one trial’, Prof
Poulter noted and he also drew attention
to an all-cause mortality benefit of
combination therapy. He questionedwhich
agents to use in combination therapy.
Trial evidence on therapeutic
agents
‘Although beta-blockers have been
recommended as therapy, they have a
weak effect on decreasing stroke and
there is an absence of effect on coronary
heart disease.’ Prof Poulter supported
this statement with results of the LIFE
comparison between losartan (ARB) and
atenolol (beta-blocker), where losartan
was found to be superior, with a 25%
reduction in stroke.
The PROGRESS trial (post-stroke
therapy in elderly patients) had significant
results for the combination of perindopril
(ACE inhibitor) with indapamide
(diuretic), showing a 28% decrease in
next stroke. Adding perindopril in the
HYVET trial of the very elderly showed
a 21% decrease in all-cause mortality,
with active treatment greatly improving
quality of life.
Prof Poulter turned his attention to the
ASCOT-BPLA trial in which amlodipine
(CCB) was found to have stroke protection
beyond the benefits of blood pressure
management. Beta-blockers (atenolol)
only had a benefit on heart rate. Of
particular interest in this trial, Prof Poulter
noted, was the relationship between blood
pressure variability, stroke and coronary
heart disease. It was found that risk of
stroke and chronic heart disease increased
with increasing blood pressure variability,
which was the measure most strongly
associated with risk.
From this, Prof Poulter concluded
that intermittent hypertension is more
dangerous than constant hypertension and
that the combination of amlodipine and
perindopril was found to be better at
controlling long-term variability of blood
pressure. Mean blood pressure in-trial has
minimal association with stroke outcome
and no association with coronary heart
disease, he pointed out.
Single-pill combinations
The advantages of single-combination
pills were highlighted by Prof Poulter,
referring to the ADVANCE trial where the
single-pill combination (ACE inhibitor
+ diuretic) had good results in type 2
diabetes patients. In the ACCOMPLISH
trial, a single-pill combination (ACE
inhibitor + CCB) was found to have
an advantage in reducing cardiovascular
events compared with an ACE inhibitor
+ thiazide. These benefits were most
evident in high-risk subjects, of whom
two-thirds were diabetic.
BHS/NICE guidelines for
anti-hypertensive therapy
Choice of first-line therapy is affected
by age. For patients younger than 55
years and of European descent, an ACE
inhibitor or ARB is recommended. For
patients older than 55 years and all black
Africans or people of Caribbean descent,
a CCB is recommended.
Second-line recommendations are dual
therapy of an ACE inhibitor or ARB +
CCB, irrespective of age or ancestry.
Third-line therapy recommends a triple-
therapy combination of ACE inhibitor
or ARB + CCB + diuretic. Prof Poulter’s
final advice, ‘most patients need two
antihypertensive agents with a statin
added to the regimen’.
J Aalbers, G Hardy
Prof Neil Poulter
Preventive Cardiovascular Medicine,
Imperial College London, currently
co-director of the International
Centre for Circulatory Health and the
Imperial Clinical Trials Unit
Prof Poulter has played a senior
management role in several inter-
national trials, including the Anglo-
Scandinavian Cardiac Outcomes Trial
(ASCOT) and the ADVANCE study.
Other research activities include the
optimal investigation and management
of essential hypertension and dyslipi-
daemia, the association between birth
weight and various cardiovascular risk
factors, the cardiovascular effects of
exogenous oestrogen and progesterone,
the aetiology and prevention of type
2 diabetes, and ethnic differences in
cardiovascular disease.
