CARDIOVASCULAR JOURNAL OF AFRICA • Vol 21, No 2, March/April 2010
AFRICA
115
Drug Trends in Cardiology
Focus on the American College of Cardiology Congress, 2010
Reduced blood pressure variability in ASCOT-BPLA trial favours use of amlodipine/perindopril
combination to reduce stroke risk
Lower within-individual visit-to-visit
variability in blood pressure readings in
the amlodipine/perindopril combination
treatment arm of the ASCOT study has
been shown to account for the more
effective stroke reduction rate with this
combination compared to atenolol and
diuretic-based therapies, despite overall
similar blood pressure lowering.
This finding was presented at the
late-breaking clinical trial session of the
American College of Cardiology congress
and was published simultaneously in the
Lancet Neurology
edition online.
1
‘These findings have major clini-
cal implications for the management
of patients with hypertension’, said
Peter Sever, FRCP, a professor of clini-
cal pharmacology and therapeutics and
co-director of the International Centre
for Circulatory Health, Imperial College,
London. ‘This data convincingly demon-
strates that patients with more variation in
their blood pressure levels are at greatest
risk of future heart attacks and strokes,
and that reducing variability is a key goal
of treatment.’
2
For the ASCOT-BPLA study, research-
ers recruited 19 257 patients with high
blood pressure, averaging 164/95 mmHg
at rest. Patients were randomly assigned
to treatment with the calcium channel
blocker amlodipine with or without the
ACE inhibitor perindopril, or to treatment
with the beta-blocker atenolol with or
without the diuretic bendroflumethiazide.
During 5.5 years of follow up, blood
pressure variability was determined by
comparing multiple blood pressure read-
ings taken at each visit and at several
different visits.
The Medical Research Council (MRC)
trial of 4 396 elderly hypertensive patients
treated with atenolol, a diuretic combina-
tion, or placebo, were also evaluated for
blood pressure variability and the results
were included in this study.
3
Researchers found that between-visit
blood pressure variability was significant-
ly greater among patients treated in the
atenolol arm than those in the amlodipine/
perindopril arm of ASCOT. In addition,
when researchers compared patients at the
highest one-tenth for between-visit blood
pressure variability to those at the lowest
one-tenth, they found a strong link with
increased risk of stroke.
In the beta-blocker group, patients
with high blood pressure variability faced
a risk of stroke 4.06 times that of those
with low blood pressure variability. In the
amlodipine/perindopril group, the risk
of stroke was 3.8 times higher among
patients with high blood pressure vari-
ability.
A similar pattern linked high blood
pressure variability to an increased risk
for heart attack and other coronary events.
The overall risk of stroke was 22% lower
among patients treated with amlodipine/
perindopril when compared to those treat-
ed with the beta blocker/thiazide diuret-
ic, a difference that could be entirely
explained by differences in blood pressure
variability, researchers found.
In the ASCOT-BPLA trial, the
researchers were also able to look at
within-visit variability and variability on
24-hour ambulatory blood pressure moni-
toring (ABPM). In the ABPM substudy,
reduced variability in daytime systolic
blood pressure (SBP) in the amlodipine
group (
p
<
0.0001) partly accounted for
the reduced risk of vascular events, but
reduced visit-to-visit variability in clinic
SBP had a greater effect.
In the MRC trial, all measures of
within-individual visit-to-visit variability
in SBP were increased in the atenolol
group compared with both the placebo
and diuretic groups during initial follow
up (all
p
<
0.0001). Subsequent temporal
trends in variability in blood pressure
during follow up in the atenolol group
correlated with trends in stroke risk.
‘The greater reduction in variability
among patients treated with amlodipine
and perindopril may be best explained
by their more profound effects on blood
vessel relaxation, compared to beta-block-
ers’, Sever said. He and his co-investiga-
tors believe that clinical guidelines and
future drug trials must take into account
the importance of blood pressure vari-
ability in the management of patients, not
simply the extent to which a drug lowers
average levels of blood pressure. This
aspect will need to be reported on in more
detail in future trials.
The hypothesis that erratic blood pres-
sure levels could be an important factor in
determining the risk of future strokes was
originally proposed by Peter M Rothwell,
MD, PhD, of the Stroke Prevention
Research Unit, University Department
of Clinical Neurology, John Radcliffe
Hospital, Oxford, UK.
J Aalbers, Special Assignments Editor
Rothwell PM,
1.
et al
. Effects of beta-blockers
and calcium channel blockers on within-
individual variability in blood pressure and
risk of stroke.
Lancet Neurol
2010, March
DOI: 10.1016/51474-4422(10)70066-1.
ACC report. ACC congress 2010.
2.
MRC working party. Medical Research
3.
Council trial of treatment of hypertension
in older adults: principal results.
Br Med J
1992;
304
: 405–412.
