Full text of DOI:10.2165/00044011-200222100-00003

Clin Drug Invest 2002; 22 (10): 667-675
1173-2563/02/0010-0667/$25.00/0
ORIGINAL RESEARCH ARTICLE
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Adis International Limited. All rights reserved.
Impact of a Low-Dose Combination of
Isradipine SRO and Spirapril on Left
Ventricular Mass and Left Ventricular
Performance in Patients with Hypertension
and Left Ventricular Hypertrophy
1
2
3
4
David Pittrow, Gottfried Weidinger, Thomas Stoerk and Hermann Eichstaedt
1
Department of Clinical Pharmacology, Medical Faculty, Technical University of Dresden,
Dresden, Germany
2
3
4
Department of Clinical Research, Novartis Pharma GmbH, Nuremberg, Germany
Department of Cardiology, Karl-Olga Hospital, Stuttgart, Germany
Department of Cardiology, Virchow-Clinic of the Charité, Humboldt-University of Berlin,
Berlin, Germany
Abstract
Objective: This study investigated the effects of a low-dose fixed combination
of the ACE inhibitor isradipine SRO (slow-release oral) and the calcium ant-
agonist spirapril on left ventricular hypertrophy (LVH) in patients with mild to
moderate hypertension and LVH.
Design: Open, non-randomised preliminary study.
Subjects: 20 patients (11 men and nine women, mean age 62 ± 12 years) with
arterial hypertension and LVH were included in the study.
Methods: ECG-triggered nuclear magnetic resonance tomography (MRT),
echocardiography and radionuclide ventriculography were used to measure para-
meters of left ventricular function at baseline and after 12 weeks’ treatment with
a fixed combination of isradipine SRO 2.5mg and spirapril 3mg once daily.
Results: Diastolic blood pressure was normalised (≤90mm Hg) after 6 weeks in
1
9 of 20 patients; only one patient required the dosage to be doubled to achieve
BP control. Mean blood pressure was reduced from 163/99mm Hg at baseline to
50/84mm Hg at the end of the study (2p < 0.001). Mean end-systolic inter-
ventricular septum thickness measured by MRT was reduced from 20.1 to
8.2mm (2p < 0.001) after 12 weeks and end-systolic left ventricular posterior
1
1
wall thickness from 19.2 to 17.7mm (2p < 0.001). Echocardiographic assessments
resulted in similar findings. The left ventricular mass index calculated from
2
echocardiographic data decreased from 195 to 164 g/m (2p < 0.001). A marked
drop in total peripheral resistance from 1470 to 1233 units (2p < 0.001) was
paralleled by a 14% decrease in systolic wall tension and an improvement in peak
ventricular filling rate. Although there was a significant reduction in left ventric-

6
68
Pittrow et al.
ular mass, parameters of cardiac work did not change significantly, thus indicat-
ing a more efficient ventricular performance during treatment.
Conclusion: In this preliminary study, a low-dose combination of isradipine and
spirapril induced a significant regression in LVH and an improvement in
haemodynamic parameters in patients with mild to moderate hypertension and
LVH. This finding needs to be confirmed in larger-scale, controlled studies.
The main cardiac response to primary hyper-
therapy.[24,25] Two studies[26,27] have recently pro-
posed another approach, namely to initiate treat-
ment with low doses of antihypertensives with
different mechanisms of action. The rationale
behind this concept is that small doses of drugs
with different modes of action used in combination
are likely to minimise the dose-dependent adverse
experiences that occur when single drugs are
titrated to their therapeutic dose levels.[
tension is concentric left ventricular hypertrophy
1]
(
LVH).[ Data from the Framingham cohort as
well as later studies have indicated that LVH is an
important independent risk factor for congestive
heart failure, coronary artery disease, stroke, ar-
[
2-5]
rhythmia and sudden death.
Hypertensive hypertrophy of the left ventricle
is not only based on a mere expansion in muscle
cell size due to an increased amount of contractile
proteins, but is also accompanied by proliferation
and structural changes in fibrous tissue,[6-8] result-
ing in impaired ventricular compliance. These
structural changes are already beginning in the
early course of hypertension and comprise myo-
28,29]
Increased interest has been expressed in the
combination of calcium antagonists and ACE
inhibitors because the effective management of
many patients with hypertension and concomitant
risk factors will almost certainly include such com-
binations.[
30]
cardial hypertrophy as well as coronary micro- and
The dihydropyridine calcium antagonist
isradipine SRO (slow-release oral) has a slow on-
set and long duration of action. In comparison with
first-generation calcium channel blockers, it offers
the advantage of minimal cardiodepressant activ-
ity, selective action on the coronary and skeletal
muscle vasculature, and prolonged vasodilatory
action.[
macroangiopathy.[
9,10]
Antihypertensive therapy
thus not only aims to normalise elevated blood
pressure (BP) but also to induce regression of
cardiac hypertrophy.
Preclinical and clinical studies have indicated
that antihypertensive agents from different classes
induce regression of LVH to a different extent,
31,32]
which is not strictly correlated to the degree of BP
Antihypertensive drugs inducing a
comparable degree of regression again differ in the
Spirapril is a new carboxyl-bearing ACE inhib-
itor.[33] It is a prodrug that is rapidly and exten-
sively metabolised into the pharmacologically
active diacid metabolite spiraprilat. The latter has
a long elimination half-life allowing once-daily
administration. It is subject to balanced biliary and
renal elimination and can thus be used in patients
reduction.[
11-16]
proportional decrease of muscle to connective
tissue.[
17,18]
In order not to impair ventricular per-
formance any further, it is most desirable to obtain
an equivalent reduction in muscle and connective
tissue.[
19,20]
Among the drugs that have been
with impaired renal function.
[34]
proven to achieve this goal to a satisfactory extent
are the ACE inhibitors and the dihydropyridine
calcium antagonists.[
Currently, the most common approaches to the
pharmacological management of hypertension are
stepped-care therapy and sequential mono-
Based on the observation that the drug classes
to which isradipine and spirapril belong effectively
induce LVH regression and improve ventricular
function, this single centre study assessed the ef-
fects of 12 weeks’ treatment with a low-dose fixed
combination of isradipine SRO and spirapril on
21-23]
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Clin Drug Invest 2002; 22 (10)

Low-Dose Isradipine/Spirapril Induces LVH Regression
669
LVH,BPand leftventricularfunctionin patients
with mild to moderate hypertension and LVH.
the calculations. Patient compliance was checked
by means of pill counting at each visit. Standard
fasting laboratory tests were performed during the
placebo phase and at the end of the study. Adverse
events were assessed at each visit by recording
spontaneous reports. Target measurements (MRT,
radioventriculography, echocardiography) were
performed at baseline and after 12 weeks.
Patients and Methods
Patients
Outpatients over 18 years of age with sitting
systolic BP (SBP) above 140mm Hg and sitting
diastolic BP (DBP) between 100 and 114mm Hg
after a 2-week placebo period as well as LVH
B-Mode echocardiography was performed
according to von Devereux and Reicheck,[ and
included the following parameters: interventricu-
lar septum thickness in systole (IVSs) and diastole
36]
[
defined as end-systolic septal thickness ≥15mm
in the sagittal axis measured by nuclear magnetic
resonance tomography (MRT) imaging] were con-
sidered for inclusion in the study. Main exclusion
criteria were the use of any antihypertensive
medication within 6 months prior to study entry,
secondary hypertension, cerebrovascular insult
less than 6 weeks previously or known cerebral
blood flow disturbances (e.g. transient ischaemic
attack), unstable angina pectoris or myocardial
infarction in the previous 3 months, heart failure
unable to be controlled by digitalis, impaired renal
or hepatic function, other serious concomitant
diseases, drug or alcohol abuse, and mental impair-
ment.
(
(
IVSd), left posterior wall thickness in end systole
PWTs) and end diastole (PWTd), left ventricular
inner diameter in end systole (LVIDs) and end
diastole (LVIDd), left ventricular muscle mass
(
LVMM) and left ventricular mass index (LVMI).
MRT was used to assess IVSs, PWTs and apical
thickness. The tomograph (Siemens Magnetom)
used a superconduction magnet operating at a field
strength of 1.5 Tesla. The Sirecust 404 electro-
cardiogram (ECG) system had ultrathin copper
leads to ensure exact end-systolic and end-dias-
tolic triggering. The repetition rate, or interval
between sets of radio frequency pulses, was deter-
mined by each subject’s heart rate and ranged from
4
00 to 1000msec. MRT scans were recorded in
Study Design and Methods
four slices and three planes (frontal, transverse and
sagittal) with multiple angulations. The imaging
sequence was pin-echo with echo delay times
of 35, 70 and 105msec and a proton resonance
frequency of 15MHz. The selection gradient was
This open, non-randomised study was approved
by the local ethics committee and patients gave
their written informed consent to take part. The
study consisted of a 2-week placebo run-in phase
and a subsequent 12-week treatment period. A
fixed combination of isradipine SRO 2.5mg and
spirapril 3mg (i.e. half of the conventional mono-
therapy daily dosages) was administered once
daily in the morning. If DBP was not normalised
after 6 weeks of therapy (i.e. DBP ≤90mm Hg), the
dosage was doubled.
3
mT/m. A 256 × 256 reconstruction matrix was
used. Angulation was started in the frontal plane
to define the correct angle in the transverse plane.
This method has been proven to be at least as
accurate as echocardiography and permits easy
reproduction of the cardiac phase measured, the
depth of the level and the angle of determina-
A complete physical examination including a
[23]
tion.
1
2-lead electrocardiogram was performed at base-
line and after 12 weeks of therapy. Sitting BP was
measured with a standard mercury sphygmo-
manometer according to the American Heart
Radionuclide Ventriculography
After in vivo marking of erythrocytes by intra-
venous administration of 10 to 20 μ/kg bodyweight
stannous pyrophosphate and 400 to 1100
megabecquerel (MBq) Tc-pertechnetat (9 TcO4–)
[
35]
Association guidelines
after a 5-minute rest,
9m
and the mean value of three measurements used in
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Clin Drug Invest 2002; 22 (10)

6
70
Pittrow et al.
over an interval of 20 to 30 minutes, a gated pool
radionuclide ventriculography was performed.
Pictures were taken via an ECG-triggered multi-
gated acquisition with a Na-iodine Crystal camera
system (APEX 115) in a modified 30° LAO-
projection with a 15° caudal-angled position. For
the exercise radionuclide ventriculography we
used a stationary cycle ergometer with an induc-
tion braking system, exercising the patient up to his
maximum steady-state frequency. The following
data were derived from this examination: total
peripheral resistance [TPR ≈ 60 × 1333 × mean BP/
viously. Baseline IVSs determined by MRT was
20.1 ± 2.8mm.
Among the 20 patients examined, only one
patient had DBP not normalised after 6 weeks’
treatment; this patient responded to the double
dosage. During the course of therapy, the mean
SBP of all patients declined from 162.6 ± 9.4 to
1
50.3 ± 14.3mm Hg (–12.3mm Hg; 2p < 0.001) and
mean DBP from 98.6 ± 3.8 to 84.1 ± 4.2mm Hg
–14.5mm Hg; 2p < 0.001). There was no signi-
(
ficant change in heart rate during the course of
therapy.
After 12 weeks’ treatment with isradipine
SRO/spirapril, MRT showed reductions in IVSs
cardiac output (CO)], systolic wall tension (Tsyst
2
=
SBP × 3√ESV ), left ventricular end-diastolic
volume (LVED), left ventricular end-systolic
volume (LVES), ejection fraction (EF), CO, peak
ejection rate (PER), peak filling rate (PFR), left
ventricular ejection time (LVET), and RR-interval.
(
1
(
from 20.1 to 18.2mm; 2p < 0.001), PWTs (from
9.2 to 17.7mm; 2p < 0.001) and apical thickness
from 22.2 to 19.6mm; 2p < 0.001) [table I].
Echocardiographic measurements confirmed these
findings, with IVSs, PWTs, IVSd and PWTd show-
ing significant regression (table II).
Statistical Analysis
We found a highly significant decline in heart
muscle mass, with LVMI dropping from 195 ± 31
In the statistical analysis, the results of the
various measurements were expressed as mean ±
SED. The differences (Δ) between baseline and
week 12 (Δ) were tested by the Wilcoxon signed
rank test, with the level of significance p < 0.05.
2
2
g/m at baseline to 164 ± 31 g/m after 12 weeks’
2
treatment (–31 g/m , p < 0.001).
There was a high correlation between wall
thicknesses measured by MRT and echocardio-
graphy. For example, correlations for IVSs before
and after treatment were r = 0.83 and r = 0.90,
respectively (figure 1 and figure 2). However,
there was no correlation between the regression of
LVMI and the decline in SBP or DBP (r = 0.03 for
LVMI/SBP and r = –0.15 for LVMI/DBP). Neither
MRT nor echocardiography showed a correlation
between the degree of LVH and the reduction in
ventricular muscle mass (r = 0.2). Assumptions
that different age subgroups influence the degree
Results
Twenty patients (11 men and nine women,
mean age 62 ± 12 years) with arterial hypertension
were included in our study. SBP ranged from 150
to 190mm Hg and DBP from 98 to 110mm Hg.
Mean bodyweight was 78 ± 10kg and did not
change significantly throughout the study. On
average, arterial hypertension had been diagnosed
3
.3 years previously, and LVH 17.3 months pre-
Table I. MRT measurements before and after 12 weeks’ treatment with a fixed-dose combination of isradipine SRO 2.5 mg/day and spirapril
mg/day in 20 patients with mild to moderate hypertension and LVH
3
Parameter (mm)
IVSs
Baseline
12 weeks
18.2 ± 2.8
17.7 ± 1.9
19.6 ± 5.4
p-Value
20.1 ± 2.8
19.2 ± 2.0
22.2 ± 5.0
2p < 0.001
2p < 0.001
2p < 0.001
PWTs
Apex
Apex = left ventricular apex wall thickness; IVS = interventricular septum thickness; LVH = left ventricular hypertrophy; MRT = magnetic
resonance tomography; PWT = posterior wall thickness; s = systolic; SRO = slow-release oral.
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Clin Drug Invest 2002; 22 (10)

Low-Dose Isradipine/Spirapril Induces LVH Regression
671
Table II. Echocardiographic measurements before and after 12 weeks’ treatment with a fixed-dose combination of isradipine SRO 2.5 mg/day
and spirapril 3 mg/day in 20 patients with mild to moderate hypertension and LVH
Parameter
Baseline
20.0 ± 2.8
19.3 ± 1.9
33.2 ± 2.7
16.8 ± 1.9
16.3 ± 1.7
49.2 ± 2.0
366 ± 46
195 ± 31
1.9 ± 0.2
12 weeks
18.2 ± 2.9
17.8 ± 1.9
31.9 ± 3.0
15.2 ± 2.4
14.9 ± 2.0
48.2 ± 2.2
308 ± 52
164 ± 31
1.9 ± 0.2
p-Value
IVSs (mm)
2p < 0.001
2p < 0.001
2p < 0.06
2p < 0.001
2p < 0.001
2p < 0.01
2p < 0.001
2p < 0.001
NS
PWTs (mm)
LVIDs (mm)
IVSd (mm)
PWTd (mm)
LVIDd (mm)
LVMM (g)
LVMI (g/m2)
Body surface area (m2)
d = diastolic; IVS = interventricular septum thickness; LVH = left ventricular hypertrophy; LVID = left ventricular inner diameter; LVMI = left
ventricular mass index; LVMM = left ventricular muscle mass; NS = not significant; PWT = posterior wall thickness; s = systolic;
SRO =slow-release oral.
PFR (both at rest and during exercise) improved
MRT
Echo
MRT
Echo
significantly after treatment in the sense of better
ventricular compliance, probably because of a
reduction in ventricular stiffness (figure 3). Rest-
ing PER improved only slightly after treatment,
although a significant improvement was seen dur-
ing exercise (figure 4). This observation is in line
with the findings for the other cardiac labour para-
r = 0.831
2
2
2
2
2
1
1
1
1
1
8
6
4
2
0
8
6
4
2
0
Echo
MRT
MRT
1
3
5
7
9
11 13 15 17 19
r = 0.903
Echo
No. of patients
2
2
2
6
4
2
Fig. 1. Comparative measurements of interventricular septum
thickness in systole by magnetic resonance tomography (MRT)
versus echocardiography (Echo) at baseline in 20 patients with
mild to moderate hypertension and left ventricular hypertrophy.
20
1
1
1
1
1
8
6
4
2
0
of LVH regression were not confirmed by our data
(
r = –0.508).
Despite the obvious regression of LVH, cardiac
1
3
5
7
9
11
13 15 17
19
output parameters remained largely unchanged at
rest as well as during exercise (table III). This is
likely to be due to a decrease in afterload arising
from a 16% reduction in TPR (from 1470 ± 271 to
No. of patients
Fig. 2. Comparative measurements of interventricular septum
thickness in systole by MRT versus echocardiography (Echo)
after 12 weeks’ treatment with isradipine SRO 2.5 mg/day and
spirapril 3 mg/day in 20 patients with mild to moderate hyper-
tension and left ventricular hypertrophy. MRT = magnetic reso-
nance tomography; SRO = slow-release oral.
1
233 ± 175U) and a 14% reduction in systolic wall
tension.
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Clin Drug Invest 2002; 22 (10)

6
72
Pittrow et al.
Table III. Radionuclide ventriculography performed at rest and under exercise before and after 12 weeks’ treatment with a fixed-dose
combination of isradipine SRO 2.5 mg/day and spirapril 3 mg/day in 20 patients with mild to moderate hypertension and LVH
Parameter
At rest
After submaximal exercise
before therapy
50.5 ± 9.3
130.8 ± 11.8
80.3 ± 7.1
6.2 ± 1.1
61.6 ± 4.8
3.6 ± 1.4
3.0 ± 1.1
week 12
p-value
before therapy
42.8 ± 12.0
127.8 ± 13.0
85.1 ± 8.8
10.4 ± 1.7
66.8 ± 6.9
3.9 ± 1.4
week 12
p-value
ns
LVESV (ml)
LVEDV (ml)
SV (ml)
49.0 ± 9.5
129.4 ± 10.4
80.5 ± 6.7
6.3 ± 1.0
62.4 ± 5.2
3.8 ±1.0
ns
40.0 ± 9.3
126.5 ± 11,9
86.5 ± 9.9
11.1 ± 1.6
68.5 ± 6.3
4.3 ± 1.1
ns
ns
ns
ns
CO (L/min)
ns
ns
LVEF (%)
ns
2p < 0.05
2p < 0.05
2p < 0.001
PER (sec–1
PFR (sec–1
)
ns
)
3.9 ± 1.0
2p < 0.001
3.3 ± 0.9
4.1 ± 0.7
CO = cardiac output; LVEDV = left ventricular end-diastolic volume; LVEF = ejection fraction; LVESV = left ventricular end-systolic volume;
LVH = left ventricular hypertrophy; ns = not significant; PER = peak ejection rate; PFR = peak filling rate; SRO = slow-release oral;
SV = stroke volume.
Discussion
4
4
4
4
3
3
.3
.2
.1
.0
.9
.8
*
Rest
Stress
LVH is recognised as a strong, BP-independent
cardiovascular risk factor.[37,38] In fact, LVH pre-
dicts complications both in members of the general
*
population[ and in patients with hypertension
39]
[40]
3.7
3.6
3.5
3.4
3.3
3.2
more strongly than any other risk factor except ad-
vancing age. These observations have provoked
great interest in how regression of LVH can be
achieved and whether different antihypertensive
agents differ in their ability to reduce myocardial
hypertrophy in addition to lowering BP.
A meta-analysis of randomised, double-blind
studies indicates that ACE inhibitors and, to a
lesser extent, calcium channel blockers emerge as
Post-therapy
Pre-therapy
Fig. 3. Changes in PFR at rest and under stress after 12 weeks’
treatment with a fixed-dose combination of isradipine SRO
.5 mg/day and spirapril 3 mg/day in 20 patients with mild to
moderate hypertension and left ventricular hypertrophy.
PFR = peak filling rate; SRO = slow-release oral; * p < 0.001 vs
pre-therapy.
2
4
3
3
2
2
.0
.5
.0
.5
.0
*
Rest
meters showing that the heart muscle did not
achieve a net increase in power during treatment
Stress
(
thus indicating a more efficient ventricular perfor-
mance).
The combination of isradipine SRO/spirapril
1.5
1
0
0.0
.0
.5
was well tolerated; no incompatibilities or serious
adverse events were reported and no withdrawals
occurred. No significant changes in the ECG or
laboratory parameters were noted. At the end of the
study, eight patients assessed the tolerability of the
medication as ‘very good’, 10 as ‘good’ and two as
Post-therapy
Pre-therapy
Fig. 4. Changes in the PER at rest and under stress after 12
weeks’ treatment with a fixed-dose combination of isradipine
SRO 2.5 mg/day and spirapril 3 mg/day in 20 patients with mild
to moderate hypertension and left ventricular hypertrophy.
PER = peak ejection rate; SRO = slow-release oral; * p < 0.01
vs pre-therapy.
‘
moderate’.
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Clin Drug Invest 2002; 22 (10)

Low-Dose Isradipine/Spirapril Induces LVH Regression
673
the drugs of choice for treating LVH and are supe-
possible to assess the relative magnitude of the
treatment effect. In addition, substantially higher
[
41]
rior to diuretics and β-blockers.
Dihydro-
pyridine calcium antagonists are functional ant-
patient numbers are needed in order to enable us
[
1]
[50]
agonists to α1- and α2-adrenergic receptors and
may therefore cause a regression of LVH. Activa-
tion of the renin-angiotensin system has been
proved experimentally to act as a trophic stimulus
to draw definite conclusions.
Our therapeutic
endpoint was the DBP level, which is usually the
case in day-to-day practice. However, it is well
acknowledged that systolic or pulse pressure rather
than diastolic pressure determines end-organ
[
42]
on the myocardial cell and similar observations
[
43]
[24,25]
have been made in humans. As a consequence,
blockade of angiotensin II with ACE inhibitors
may contribute (independent of any BP-lowering
effect) to the reversal of myocardial hyper-
trophy.[
damage in hypertensive patients.
Bias was reduced by the fact that objective vari-
ables with different recognised methods were in-
vestigated.[ In addition to echocardiography, as
the most widespread imaging method used for
measuring cardiac wall thicknesses, we also used
multislice gated multiplanar MRT.[ Gated MRT
can generate excellent morphological contrast and
permits easy reproduction of measured cardiac
51]
44]
So far, the impact of isradipine and spirapril on
LVH has only been investigated in monotherapy
studies. In an open study in 15 previously untreated
patients with hypertension, 6 months’ treatment
with isradipine 2.5 to 10 mg/day caused a signi-
52]
phases, slice thickness and angle of determina-
[
45]
[53]
ficant reduction in mean LVMI of 17%.
In an-
tion.
In comparison with echocardiography,
other open study in 25 patients with moderate
hypertension, 3 months’ treatment with isradipine
MRT provides improved images and permits supe-
rior accuracy of measurements. However, it must
be said that in a recent study a systematic under-
estimation of LV mass by MRT was seen.[
The data derived from both methods indicate
that the low-dose combination of a calcium ant-
agonist and an ACE inhibitor is able to induce a
substantial regression of LVH in patients with mild
to moderate hypertension. Left ventricular mass
was reduced by 16% after only 3 months’ treat-
ment and it is likely that the magnitude of the
effect increases after longer treatment periods.
These results are in line with other clinical trials
2
.5 to 5 mg/day (and, if necessary, add-on of
54,55]
hydrochlorothiazide) resulted in a 22% reduction
in LVMI.[
46]
Comparable results were observed
after 6 months’ treatment with once daily sus-
tained-release isradipine 5mg in an open pilot
study in 12 hypertensive patients with LVH and
[
47]
normal LV diastolic diameter.
Administration of normal to high dosages of
spirapril (6 to 24 mg/day) to 11 patients with
hypertension for 3 to 36 months effectively re-
duced parameters of left ventricular hyper-
trophy,[ as it did in another study when admin-
istered at a dosage of 6 mg/day for 20 weeks to 28
48]
showing a 7.8 to 17% reduction in LVH after treat-
ment with ACE inhibitors[
21,48,49,52,56,57]
and a
[
49]
patients with mild to moderate hypertension.
reduction in left ventricular mass of 11 to 19%
with calcium antagonists.[
45,56,58,59]
In the present exploratory study both agents in
combination, despite the low dosages used, were
able to induce a significant regression in LVH.
When discussing the results, some methodological
considerations have to taken into account. In prin-
ciple, double-blind, randomised study designs are
preferable. The present trial was open and non-
randomised and therefore may be prone to bias. In
the absence of a control group such as a low-dose
combination of a β-blocker and a diuretic it is not
The drug combination used in this study con-
tained half the standard dosage of both isradipine
and spirapril, and matched the level of BP control
and LVH regression usually achieved with stand-
ard dosages of either agent.[
45,46,49]
With regard to the haemodynamics, the combi-
nation effectively reduced TPR by 16% from base-
line and thus lowered the systolic ventricular wall
tension by about 14%. The PFR (a measure of ven-
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Clin Drug Invest 2002; 22 (10)

6
74
Pittrow et al.
1
2. Cruickshank JM, Lewis J, Moore V, et al. Reversibility of left
ventricular hypertrophy by different types of antihypertensive
therapy. J Hum Hypertens 1992; 6: 85-90
tricular stiffness and LVH) improved at rest and
under stress and mean heart rate and PER remained
unchanged at rest. The combination therefore did
not appear to cause adrenergic stimulation, but
maintained cardiac performance and workload on
a more efficient and economic level.
13. Eichstädt H, Danne O, Langer M, et al. Regression of left
ventricular hypertrophy under ramipril treatment investigated
by nuclear resonance imaging. J Cardiovasc Pharmacol 1989;
13 Suppl. 3: 75-80
1
4. Motz W, Strauer BE. Regression of structural cardiovascular
changes by antihypertensive therapy. Hypertension 1984; 6
Suppl. 3: 133-9
Conclusion
15. Eichstädt H, Schröder R, Richter W, et al. Untersuchungen zur
Regression der linksventrikulären Hypertrophie - Messungen
unter einer Kombinationstherapie von Co-Dergocrinmesilat
und Nifedipin mittels Magnetresonanztomographie bei
Patienten mit arterieller Hypertonie. Herz Kreisl 1991; 23
Suppl. 12: 421-4
According to this pilot study, a once-daily low-
dose combination of isradipine SRO and spirapril
appears able to induce regression of LVH to a
substantial degree and improve ventricular perfor-
mance in patients with mild to moderate hyper-
tension. Larger-scale studies are warranted to
confirm these preliminary findings.
1
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Correspondence and offprints: Dr David Pittrow, Institute
of Clinical Pharmacology, Medical Faculty, Technical
University of Dresden, Fiedlerstrasse 27, Dresden, D-01307,
Germany.
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tricular hypertrophy following treatment of hypertension
E-mail: david.pittrow@mailbox.tu-dresden.de
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Adis International Limited. All rights reserved.
Clin Drug Invest 2002; 22 (10)