CARDIOVASCULAR JOURNAL OF AFRICA • Vol 21, No 1, January/February 2010
AFRICA
61
24-hour powerful blood pressure lowering – essential for target
organ protection
Circadian blood pressure rhythm is
controlled by intracellular molecular
clocks, which allow the body to prepare
for anticipated stimuli, the morning blood
pressure surge helping to meet the chal-
lenges of the day while the nocturnal
blood pressure fall sets the system for a
period of rest.
These rhythms vary in hypertensive
and non-hypertensive individuals (Fig. 1).
1
Cardiovascular outcomes are worsened in
individualswhohave anexcessivemorning
blood pressure surge and in those who lack
the normal nocturnal blood pressure fall.
This early morning blood pressure
surge has also been shown in epide-
miological studies to result in a clus-
tering of cardiovascular complications
such as stroke,
2
myocardial infarction
3
and
coronary ischaemia
4
around this morning
period. This increased risk of cardiovas-
cular events has been shown to occur also
in elderly hypertensives.
5
Early morning blood pressure surg-
es occur in both poorly controlled and
well-controlled hypertensives; with poor
blood pressure control being associated
with uncontrolled morning blood pres-
sure levels in 70% of patients in the
ACAMPA study (Analysis of the Control
of blood pressure using Ambulatory
Blood Pressure monitoring).
6
Few antihypertensives are sufficiently
long acting to sustain adequate blood
pressure lowering for the full 24 hours
between once-daily doses, and indeed
many are at their lowest efficacy during
the risky early morning period. The angio-
tensin receptor blocker (ARB) telmisartan
has the longest plasma half-life, high-
est lipophilicity, highest receptor binding
affinity, and slowest dissociation of any
ARB, making it particularly suitable for
sustained 24-hour blood pressure control.
An important measure of 24-hour
blood pressure control is the smoothness
index (SI), which is considered to be a
better indicator of blood pressure homo-
geneity over time.
7
The SI is calculated
by using the average of hourly changes in
blood pressure over 24 hours, divided by
the standard deviation. SI values greater
than one indicate a reliable and sustain-
able effect over 24 hours.
A recent meta-analysis,
8
which
assessed the SI for standard daily doses
of drugs from different classes showed
that telmisartan has an SI higher than
that of losartan, valsartan or ramipril, and
equivalent to the SI of the long-acting
antihypertensive amlodipine.
The predictive value of telmisartan’s
SI of 1.13 systolic blood pressure (SBP)
and 0.97 diastolic blood pressure (DBP)
and the provision of 24-hour protection
is supported by the results of two major
trials, theMICADO II study
9
and PRISMA
I and II studies.
10,11
The MICADO II study
showed telmisartan (80 mg) has a more
powerful SBP reduction throughout the
24-hour period compared to valsartan
(160 mg; recommended dose).
In the PRISMA I and II studies
(Prospective, Randomized Investigation
of the Safety and efficacy of telmisar-
tan vs ramipril using Ambulatory BP
Monitoring), in which patients with
mild-to-moderate hypertension (95–109
mmHg seated DBP) were randomised to
once-daily treatment with telmisartan 80
mg or ramipril 5 mg force-titrated to 10
mg, researchers found that the reductions
in both SBP and DBP during the last six
hours of the dosing interval were signifi-
cantly greater with telmisartan 80 mg
than with ramipril 10 mg (
p
<
0.0001).
Similar findings were observed through-
out the 24-hour dosing period.
Prescribing antihypertensives such as
telmisartan with a prolonged duration
of action not only provides blood pres-
sure lowering during the vulnerable early
morning hours but also mitigates against
the loss of blood pressure control if a dose
is missed. In a pooled analysis of two
studies comparing telmisartan 80 mg with
valsartan 160 mg once daily during the
24 hours after a missed dose in patients
with mild-to-moderate hypertension
(MICADO I and II studies), telmisartan
sustained blood pressure control after a
missed dose significantly better than with
valsartan (
p
<
0.05 daytime;
p
<
0.001
night time), an effect that was particularly
marked during the last six hours of the
dosing interval (
p
<
0.0001).
In conclusion, clinical studies have
shown that telmisartan provides 24-hour
blood pressure control superior to that
Fig. 1. Circadian variations in hypertensive (top curve) and normotensive
(lower curve) individuals.
150
120
Nocturnal fall
Morning BP surge
0
6
12
24h
Non-dipping pattern
Normal circadian BP rhythm
Waking
Systolic blood pressure (mmHg)
Adapted from Schachter M
. Br J Cardiol, 2004;
11
(4): 287–290
with permission.
