ORIGINAL ARTICLE

Safety and Effectiveness of Candesartan and Candesartan/

HCT Fixed Dose Combination in Patients with Hypertension

Arini Setiawati1,2, Taufik Pohan3

1
Clinical Study Unit, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia. 2 Department of Pharmacology
and Therapeutics, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia. 3 Department of Cardiology,
Pondok Indah Hospital, Jakarta, Indonesia.

Correspondence mail:
Clinical Study Unit, Faculty of Medicine Universitas Indonesia. Jl Salemba 6, Jakarta 10430, Indonesia.
email: arinisetiawati@yahoo.com.

ABSTRAK
Tujuan: untuk menilai keamanan dan efektifitas candesartan dan kombinasi tetap (KT) candesartan/HCT
pada pasien hipertensi dalam praktek klinik sehari-hari. Metode: suatu studi terbuka observasional dengan masa
pengobatan selama 12 minggu. Tablet candesartan 4 mg, 8 mg, atau 16 mg, atau candesartan/HCT 16/12,5 mg
diresepkan untuk pasien hipertensi dewasa, yang belum pernah diobati (naïve) dan sudah diobati sebelumnya
tetapi tidak terkontrol, tergantung pada dokter yang merawat berdasarkan penilaiannya pada kondisi klinik
pasien yang bersangkutan. Hasil: dari total 112 pasien naïve dan 381 pasien yang sudah diobati sebelumnya,
yang memenuhi syarat untuk analisis keamanan, hanya ada 3 pasien dengan kejadian tidak diinginkan, dan
2 di antaranya diperkirakan mungkin disebabkan oleh candesartan (0,41%) dan tidak ada kejadian tidak
diinginkan yang serius. Kedua pasien tersebut sudah diobati sebelumnya, satu pasien mengalami nausea, dan
pasien yang lain mengalami parestesia. Candesartan dan candesartan/HCT efektif dalam menurunkan TDS
dan TDD dari baseline pada minggu 4, 8 dan 12, pada kedua kelompok, dengan penurunan TDS sebesar 26–27
mm Hg pada minggu 12 dan cenderung lebih besar pada pasien naïve dibandingkan pada pasien yang sudah
diobati sebelumnya, meskipun tidak berbeda bermakna. Akan tetapi, pencapaian TD <140/90 mm Hg antar
kelompok berbeda bermakna pada minggu 8 (56% v.s. 40%; p=0,003) dan minggu 12 (69% v.s. 53%; p=0,004).
Candesartan dan candesartan/HCT juga efektif untuk pasien hipertensi yang tidak terkontrol dengan terapi
antihipertensi sebelumnya selama >4 tahun (>50% di antaranya menjadi terkontrol). Kesimpulan: hasil studi
terbuka observasional ini menunjukkan bahwa candesartan dan candesartan/HCT ditoleransi dengan baik dan
efektif pada pasien hipertensi yang belum pernah diobati maupun pada pasien hipertensi yang sebelumnya
sudah diobati tetapi tidak terkontrol.

Kata kunci: candesartan, kombinasi tetap candesartan/HCT, hipertensi.

ABSTRACT
Aim: to assess the safety and effectiveness of candesartan and candesartan/HCT fixed-dose combination
(FDC) in patients with hypertension in daily clinical practice. Methods: an open observational study with a
12-week period of treatment. Candesartan tablets of 4 mg, 8 mg, or 16 mg, or candesartan/HCT FDC tablets
(16/12.5 mg) were prescribed to adult hypertensive subjects, both treatment-naïve patients and previously
treated but uncontrolled patients, depending on the physicians’ discretion based on his/her judgment on the
clinical condition. Results: from a total of 112 treatment-naïve patients and 381 previously treated patients
eligible for safety analysis, there were only 3 patients with adverse events, and 2 of which were considered
possibly related to candesartan (0.41%) and there were no serious adverse events. Both patients were previously

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treated patients, one patient experienced nausea and the other patient experienced paresthesia. Candesartan
and candesartan/HCT were effective in lowering systolic blood pressure (SBP) and diastolic blood pressure
(DBP) from baseline at weeks 4, 8, and 12, in both groups, with 26-27 mm Hg decreases in SBP at week 12
and a trend toward a larger reduction in treatment-naïve patients than in previously treated patients, although
not statistically significant. However, in terms of patients achieving a BP of <140/90 mm Hg between groups
were significantly superior in treatment-naïve patients than in previously treated patients at week 8 (56% vs
40%; p = 0.003) and week 12 (69% vs 53%; p=0.004). Candesartan and candesartan/HCT were also effective
for patients with long-standing (>4 years) uncontrolled hypertension with previous antihypertensive therapy,
which was most commonly calcium channel blockers (became controlled in >50% of all uncontrolled patients).
Conclusion: results of this open observational study showed that candesartan and candesartan/HCT were well
tolerated and effective in both treatment-naïve patients and uncontrolled hypertensive patients with previous
antihypertensive treatment.

Key words: candesartan, candesartan/HCT fixed, hypertension.

INTRODUCTION
Hypertension is a major risk factor for
cardiovascular diseases, and the purpose of
antihypertensive treatment is to reduce morbidity
and mortality of cardiovascular disease resulted
from hypertension. With increasing age, diastolic
blood pressure (DBP) increases until about
the age of 60, while systolic blood pressure
(SBP) continues to rise.1 Blood pressure (BP)
reductions of 10 mm Hg systolic or 5 mm
Hg diastolic are associated with a 33 to 48%
reduction in stroke and a 17 to 27% reduction
in CHD events.2
The renin-angiotensin-aldosterone system
(RAAS) plays an important role in the regulation
of blood pressure and the development of
hypertension, atherosclerosis, heart failure, type
2 diabetes mellitus, and renal disease. ACE-
inhibitors (ACEIs) and angiotensin receptor
blockers (ARBs) decrease BP, and improve
heart failure. Both ACEIs and ARBs generally
have the same indications, contraindications,
precautions, and adverse events, except for the
incidence of dry cough, which is very high for
ACEIs and very low for ARBs.3 In JNC-6, 19974,
ARBs were used only for patients intolerant of
ACEIs due to dry cough.
In JNC-7, 20035, ARBs have become one
of the five first-line drugs for hypertension. It
was also mentioned that when BP is more than
20/10 mm Hg above goal, consideration should
be given to initiating therapy with two drugs,
either as separate prescriptions or as fixed dose
combinations.
The present study assessed the use of
candesartan and candesartan/HCT FDC for
hypertensive patients in daily clinical practice.
The primary objective of this study was to
assess the safety of candesartan (Blopress®)
and candesartan/HCT FDC (Blopress Plus®)
in patients with hypertension in daily practice.
The secondary objective was to evaluate the
effectiveness of candesartan and candesartan/
HCT FDC in patients with the same condition.
METHODS
The plan was to recruit 1000 patients from
200 participating physicians in from several big
cities in Indonesia.
Men and women, age >18 years, with
uncomplicated essential hypertension, sitting
diastolic BP (sDBP) >90 mm Hg and/or sitting
systolic BP (sSBP) >140 mm Hg were recruited
for this study. They were (i) newly diagnosed
hypertensive patients not previously treated
(treatment-naïve patients), (ii) hypertensive
patients previously treated but uncontrolled, (iii)
patients previously treated with candesartan at
a lower dose but now requiring either a higher
dose of candesartan or candesartan/HCT FDC,
or (iv) hypertensive patients previously treated
but intolerant of the side effects (for these latter
patients there were no limits for sDBP or sSBP).
The decision to enter a patient into this study
was purely based on clinical consideration of the
physician. Excluded from the study were patients

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who were hypersensitive to any component of
the study drugs; pregnant or nursing women;
and patients with cholestasis or severe renal or
hepatic impairment, refractory hypokalemia or
hypercalcemia, gout, or any condition that in
the opinion of the physician would jeopardize
the safety of the patients and/or effectiveness of
the study drugs.
Study Design and Procedure
This was an open observational, multi-
centre study with a 12-week treatment period.
The study protocol was approved by the
Ethics Committee of the Faculty of Medicine,
Universitas Indonesia.
Safety and tolerability were observed
throughout the study period, particularly during
recommended visits (visit 2, 3, and 4, at week 4,
8, and 12, respectively).
Blood pressure measurements were
performed at visit 1, 2, 3, and 4 at the participating
physician’s office or clinic.
The recommended initial dose for treatment-
naïve patients was 4 mg (1/2 tablet of candesartan
8 mg) taken orally once daily, and the dose
could be uptitrated at every follow up visit
(visit 2, 3 and 4). However, the physician could
also determine proper initial dose depending
on patient’s condition. Different schedules of
uptitration from the recommended protocol
could be applied by the physician based on
medical consideration during the study period
whenever the target BP was not yet achieved.
For patients who were not yet controlled with
previous antihypertensives, the initial dose was
at the physician’s discretion.
The study drugs were candesartan 8
mg tablets, candesartan 16 mg tablets and
candesartan/HCT 16/12.5 mg tablets. These
medications were given once daily for 12 weeks.
The medications were recommended to be taken
preferentially in the morning independent of
mealtime.
Concomitant medications for non-
hypertensive therapy could be given at the
discretion of the physician, and these medications
were recorded in the case report form (CRF).
Every patient had the right to discontinue
his/her participation in the study at any time
without giving the reason. All data generated
up to the time of discontinuation from the study
were recorded and analyzed, including reasons
for the discontinuation (if it could be obtained).
At baseline, patients were selected based on
the inclusion and exclusion criteria, and then
the following data were collected: patient’s
age, gender, and physical examination findings.
Included in the medical history were the onset
date of hypertension and all antihypertensive
drugs taken in the last 3 months. The blood
pressure was measured in sitting position after 5
minutes rest with a mercury sphygmomanometer.
Two measurements were minimally performed at
each visit and the average value was recorded.
The physician recorded all adverse events/side
effects reported by patients in the CRF.
At visits 2, 3 and 4 (weeks 4, 8, and
12), the investigators assessed the following
related to safety/tolerability and effectiveness
of the study drugs and recorded in the CRF:
blood pressure, concomitant drugs, safety and
tolerability. The physician recorded all adverse
events/side effects, either new or continuing,
reported by patients into the CRF. If an adverse
event occurred, either serious or nonserious,
the physician also had to complete the available
CIOM form (according to the SOP of Takeda).
Safety Assessment
Safety assessment consisted of monitoring
and recording adverse events (AEs), including
serious adverse events (SAEs). Information
of all AEs, either volunteered by the patient,
questioned by the physician, or detected through
physical examination, laboratory tests or other
means, were collected and recorded in the CRF.
An adverse event (AE) means any adverse
medical event which occurs in a patient or clinical
trial subject who receives a pharmaceutical
product irrespective of causal relationship with
the product given. Therefore, an adverse event
may be a sign (including abnormal laboratory
test), symptom, or unexpected or untoward
disease which occurs during the use of a drug,
irrespective of its relationship with the drug.
A previous medical condition before starting
the study drug is only considered as an AE
when the condition worsens after starting the
study drug. An abnormal laboratory result or
other test result is considered as an AE only
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Arini Setiawati
when the laboratory value worsens or induces
clinical sign or symptom, which is clinically
significant, requiring therapy, or results in study
discontinuation of the patient; and this data is
recorded in the CRF based on the related sign,
symptom or diagnosis.
Pregnancy, overdose, or drug abuse that
occur during study participation must also be
reported.
An SAE means any untoward medical
occurrence, irrespective of its relation to the
study drug or the dose administered, that
results in death, is life-threatening, requires
inpatient hospitalization or prolongation of
existing hospitalization, results in permanent
or significant disability or incapacity, results in
a congenital anomaly/birth defect, or requires
intervention to prevent one of the above events
or may endanger the patient although the
occurrence is not life-threatening or fatal or
does not result in inpatient hospitalization, and
written in “List of Medically Significant Side
Effect Takeda” (According to the relevant SOP
of Takeda).
Efficacy Analysis
Patients were classified into two groups,
i.e. (a) treatment-naïve patients and (b) patients
493 patients recruited
461 were eligible for efficacy analysis
110 treatment -naive
12 discontinued:
7 uncontrolled BP
3 move to other city
1 visit another physician
1 repeated chest pain
110 analyzed for efficacy
Figure 1. Disposition of patients
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Acta Med Indones-Indones J Intern Med
already treated with antihypertensive drugs but
not yet controlled (including candesartan and
non-candesartan regimens).
Changes in sSBP and sDBP from baseline
at visit 2 (week 4), visit 3 (week 8) and visit 4
(week 12) were analyzed in each group using
Wilcoxon test, and the differences between
groups were also analyzed using Mann-Whitney
test.
The percentages of patients achieving
target BP of <140/90 mm Hg at each visit were
compared between groups using chi-square test.
RESULTS
Starting in September 2009 and ending in
July 2011, a total of 493 patients were recruited,
and 461 patients were eligible for efficacy
analysis. Fourteen patients had BP of <140/90
mm Hg after repeated measurements and 18
patients had gouty arthritis, which excluded them
from this study. Therefore 493 patients were
the safety population and 461 patients were the
efficacy population.
From a total safety population of 493 patients,
consisting of 112 treatment-naïve patients and
381 patients with previous antihypertensive
drugs, adverse events occurred in only 3 patients
32 were excluded:
14 had BP < 140/90 mm Hg
18 had gouty arthritis
351 previously -treated
18 discontinued:
12 uncontrolled BP
1 move to other city
1 visit another physician
2 patient’s request
2 expensive drug
351 analyzed for efficacy
Vol 45 • Number 3 • July 2013 Safety and effectiveness of Candesartan and Candesartan/HCT fixed dose
Table 1. Demographics and baseline characteristics
Total
(N = 461)
Males: n (%) 243 (52.7)
Age (yr): mean (SD) 54.5 (11.20)
Weight (kg): mean (SD) 66.2 (11.67)
BMI (kg/m2): mean (SD) 25.0 (3.54)
Diagnosis (yr): mean (SD) 3.7 (5.40)
Diabetes : n (%) 42 (9.11)
(0.61%) and there was no serious adverse
event found. Nausea and paresthesia, possibly/
probably related to candesartan (according to the
investigators), each occurred in one patient with
previous antihypertensive drugs. Repeated chest
pain with a normal ECG occurred in one naïve
patient, it was considered by the investigator as
not related to candesartan.
From the total efficacy population of 461
patients, 110 (24%) were recently diagnosed
with hypertension and had not received
any antihypertensive drug (treatment-naïve
patients), while 351 (76%) were already on
antihypertensive treatment but either the blood
pressure had not yet controlled (>140/90 mm
Hg) or the current antihypertensive therapy
caused disturbing adverse drug reactions.
Male patients were only slightly more
prevalent than female patients (52.7% versus
47.1%), mean age was 54.5 years, and mean
weight was 66.2 kg. Patients with previous
antihypertensives were older than naïve patients,
with similar weight and BMI. There were
18.7% elderly patients, and 8.2% overweight
and obese patients. Patients with previous
antihypertensives had been diagnosed for a
mean duration of 4.4 years but the BP had not
yet controlled.
On physical examination, 426 patients
(92.4%) had normal findings. The abnormalities
in 35 patients (7.6%) were as follows: post-stroke
with hemiparesis in 10 patients (1 naïve patient
and 9 patients with previous antihypertensive
drugs), followed by signs of heart disease in 9
patients (1 naïve and 8 patients with previous
antihypertensive drugs), obesity in 3 patients
Patients with previous
Treatment-naive patients
antihypertensive treatment
(n = 110)
(n = 351)
58 (52.7) 185 (52.7)
52.2 (10.79) 55.2 (11.24)
65.7 (12.19) 66.3 (11.53)
24.5 (3.52) 25.1 (3.53)
1.2 (3.82) 4.4 (5.58)
6 (5.5) 36 (10.3)
(all with previous antihypertensive drugs), and
other findings in 13 patients (5 naïve and 8 with
previous antihypertensive drugs).
A total of 30 patients discontinued from
the study, 12 patients from the treatment-naïve
group and 18 patients from the previously
treated group. The most frequent reason for
discontinuation was uncontrolled hypertension,
7 patients from treatment naïve group and 12
patients from previously treated group.
Eligible patients received a prescription
of candesartan tablets (4 mg, 8 mg, 16 mg) or
candesartan/HCT (16/12.5 mg) once daily in the
morning, depending on physician’s discretion
based on his/her clinical judgement on the
clinical condition of the patient. Uptitration
was done every 4 weeks (as required) until
12 weeks (final visit) or until goal BP was
achieved (<140/90 mmHg. Since this was an
observational study, there was no intervention
from the investigator.
Among 351 patients with previous
antihypertensive drugs, calcium channel
blockers were the predominant drugs (47.0%),
followed by ACE inhibitors (28.5%) and
angiotensin receptor blockers (24.2%).
Concomitant antihypertensive drugs were
listed in Table 2, and concomitant drugs other
than antihypertensives in Table 3.
Table 2. Concomitant antihypertensives (n = 87/461)
Antihypertensives n (%)
Calcium channel blockers 48 (10.4)
ACE inhibitors 16 (3.5)
b-blockers 12 (2.6)
Diuretics 11 (2.4)
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When using or after switching to candesartan Effects of candesartan on blood pressure

or candesartan/HCT, less than 20% of patients in treatment-naïve and in previously treated
required concomitant antihypertensives, and patients can be seen in Table 4 and Figures 2
a majority of these patients were on calcium and 3.
channel blockers. The decreases in SBP and DBP were
similar between treatment-naïve patients and
Table 3. Concomitant drugs other than antihypertensives patients with previous antihypertensive drugs,
(N = 461)
at 4 weeks, 8 weeks, and 12 weeks. However, a
Concomitant drugs N (%) greater percentage of treatment-naïve patients
Oral antidiabetics 51 (11.1) were brought to a BP <140/90 than previously-
Lipid lowering drugs 45 (9.8) treated patients at week 8 and week 12.
Antiplatelet drugs 25 (5.4) For all patients in the present study, the
Hypnotic sedatives and other CNS drugs 20 (4.3) effects of candesartan on blood pressure based
Vitamins & Minerals 19 (4.1) on doses at week 12 are shown in Table 5, and
Gastrointestinal drugs 14 (3.1) the majority of patients ended up on a dose of 8
NSAIDs 12 (2.6) mg candesartan monotherapy.
Analgesics 8 (1.7)
Antiasthmatic drugs 5 (1.1) DISCUSSION
Cardiac drugs 4 (0.9)
This study was an open observational
Others 42 (9.1)
study to assess the safety (primary objective)
and effectiveness (secondary objective) of
The concomitant drugs other than candesartan and candesartan/HCT FDC for the
antihypertensives were dominated by oral treatment of hypertensive patients in clinical
antidiabetics, followed by lipid lowering drugs daily practice in Indonesia.
and antiplatelet drugs.

Table 4. Effects of candesartan on BP in treatment-naïve and previously treated patients (mm Hg)
Treatment-naïve pts Pts with previous Between group comparison
(n=110) antihypertensive (between differences from
medications (n=351) baseline)
Week SBP DBP SBP DBP Mann-Whitney test
Week 0 (mean) 157.4 96.6 160.3 96.7
Week 4 (mean) 140.5 88.0 145.7 88.7
Diff. from week 0 (mean) -16.9 - -14.6 - SBP: Z=1.57 (NS)
- -8.6 - -8.0 DBP: Z=1.37 (NS)

Wilcoxon test (Z) -8.27 -7.95 -15.06 -13.64

p-value <0.001 <0.001 <0.001 <0.001
BP <140/90 33 (30%) 82 (23%) X2=1.63; p=0.2 (NS)
Week 8 (mean) 134.4 84.8 139.4 85.4
Diff. from week 0 (mean) -23.0 - -20.9 - SBP: Z=1.60 (NS)
Wilcoxon test (Z) -8.77 -8.54 -15.28 -14.38 DPB: Z=0.89 (NS)
p-value <0.001 <0.001 <0.001 <0.001
BP <140/90 62 (56%) 140 (40%) X2=8.58; p=0.003
Week 12 (mean) 129.8 82.3 134.1 83.9
Diff. from week 0 (mean) -27.6 - -26.2 -
SBP: Z=1.13 (NS)
- -14.3 - -12.8
DBP: Z=1.61 (NS)
Wilcoxon test (Z) -8.91 -8.95 -15.80 -14.61
p-value <0.001 <0.001 <0.001 <0.001
BP <140/90 76 (69%) 186 (53%) X2=8.58; p=0.004

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tract. Candesartan is one of the ARBs that has

Figure 2. Effects of candesartan on BP in treatment-naïve
and previously treated patients at weeks 4, 8, and 12
Figure 3. BP <140/90 mm Hg) in treatment-naïve and
previously treated patients at weeks 4, 8, and 12
In this 12-week study, the patients either used,
or switched to, candesartan or candesartan/ HCT.
Candesartan cilexetil is converted to candesartan
during absorption from the gastrointestinal
competitive binding with angiotensin II to the
AT1 receptor with high affinity. The affinity of
candesartan for the AT1 receptor is 80 times that
of losartan.6 Candesartan has four binding sites
on the AT1 receptor, while losartan has only two
binding sites.7 The dissociation half-life from
the AT1 receptor is 152 minutes for candesartan
and 5 minutes for losartan.8 Candesartan’s tight
binding to and slow dissociation from AT1
receptor provides insurmountable antagonism
and inverse agonism9, producing more potent
inhibition of AT1 receptors.10
A total of 1000 patients from 200 physicians
were planned (5 patients per physician), but only
493 patients were recruited and 461 patients
were eligible for efficacy analysis.
From a total of 112 treatment-naïve patients
and 381 previously treated patients eligible for
safety analysis, there were only 2 patients with
adverse events (0.41%), one patient experienced
nausea and the other patient experienced
paresthesia. Both patients were previously
treated patients and both adverse events were
considered possibly related to candesartan.
This was consistent with ARBs in general: well
tolerated and comparable to placebo.10
Twelve among 110 naïve patients (10.9%)
and 18 among 351 previously treated patients
(5.1%) discontinued from the study, mostly due
to uncontrolled hypertension (7 naïve and 12

Table 5. Effects of candesartan on BP (mm Hg) based on doses at week 12

Cand/HCT (16/12.5 mg)

Doses at week 12 4 mg (n=25) 8 mg (n=279) 16 mg (n=104)
(n=49)
SBP (mm Hg)
Wk 0 (mean) 158.7 156.9 164.7 164.2
Wk 12 (mean) 128.4 132.1 136.1 134.4
Diff. from wk 0 (mean) -30.3 -24.8 -28.6 -29.8
Wilcoxon test (Z) -4.373 -14.110 -8.631 - 5.828
p value <0.001 <0.001 <0.001 <0.001
DBP (mm Hg)
Wk 0 (mean) 95.8 95.9 98.9 97.4
Wk 12 (mean) 79.6 83.4 85.0 83.5
Diff. from wk 0 (mean) -16.2 -12.5 -13.9 -13.9
Wilcoxon test (Z) -3.948 -13.424 -8.336 -5.336
p value <0.001 <0.001 <0.001 <0.001
Target BP <140/90 18 (72%) 164 (59%) 53 (51%) 26 (53%)
From the total of 461 patients, 4 patients did not have the drug doses at week 12 recorded

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Arini Setiawati
previously treated patients).
In a meta-analysis including 13 trials
between 1980 and 2008, candesartan was shown
to be more effective than losartan.11 Candesartan
was also shown to have similar or even greater
efficacy compared with enalapril or HCT12, and
a similar efficacy to amlodipine13,14 with less
side-effects. Candesartan/HCT was known to
be more effective than candesartan alone15,16,
and that this dual antihypertensive therapy
has additive action, producing high efficacy,
similar to amlodipine17, and was effective in
treating severe hypertension18, while being well
tolerated.
Data from 72 Swedish primary care centers
involving adult hypertensives without CVD
where patients received candesartan or losartan
as antihypertensives and were followed for up to
9 years, were analysed with two different study
objectives by a same group of investigators.19,20
Both studies compared the effects of candesartan
vs losartan as the primary treatment of
hypertension;one study investigated the various
cardiovascular events19, while the other study
investigated the various subgroups of patients.20
There was no difference in BP reduction in
these studies; but compared with losartan,
candesartan produced lower hazard ratio for
total CVD, heart failure, and peripheral artery
disease.19 Furthermore, compared with losartan,
candesartan also reduced the risk of all CVDs
(primary composite endpoint), irrespective of
sex, age, previous antihypertensive treatment,
baseline blood pressure, and presence of
diabetes.20 These reductions in hazard ratios
by candesartan might be attributed to the tight
binding of candesartan to the AT1 receptor,
leading to more potent inhibition of this receptor
by candesartan.19,20 This clinical efficacy was in
line with the preclinical data and clinical profile
mentioned previously.6-10
In the present observational study, within
the treatment-naïve group and the previously
treated group, the majority of patients ended
up on a dose of 8 mg candesartan; and overall,
candesartan or candesartan/HCT was effective
in lowering the BP from baseline (p<0.001 for
both SBP and DBP) at 4-, 8- and 12-week visits
(Table 4 and Figure 2). However, comparing
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Acta Med Indones-Indones J Intern Med
between these 2 groups, the SBP and DBP
reductions from baseline were not significantly
different (Table 4).
It should be noted, however, that many
patients in both groups apparently remained
uncontrolled with sub-maximal therapy at 12
weeks, as only 69% and 53% of naïve and
previously treated patients, respectively, had BP
<140/90 mm Hg; and only 49 patients (10.6%)
were on candesartan/HCT at the end of the
observation period. While this might be because
12 weeks is not enough time for titration-to-
target, or the concern of the physicians that
many patients may not tolerate a higher level of
therapy; it seems simply to reflect the real-world
interest of physicians in escalating therapy.
Nevertheless, this showed the effectiveness
of candesartan in actual clinical practice in
Indonesia.
There were four additional points that should
be noted from these study results. First, although
the mean BP reductions were not significantly
different between the two groups, the percent
of patients achieving BP of <140/90 mm Hg
was higher in the treatment-naïve group than
in the previously treated group at weeks 8 and
12. Second, the diagnosis of previously treated
patients was an average of 4.4 years, and yet their
BPs were still uncontrolled. In more than 50%
of these patients, BP could now be controlled
with candesartan or candesartan/HCT at week
12 (Table 4). Third, almost half of the previous
antihypertensives were CCBs, and about half
were ACEIs and ARBs, all of these patients
had not reached the BP of <140/90 mm Hg, and
more than 50% of these patients reached that
BP after receiving candesartan or candesartan/
HCT at week 12. These latter two points show
that candesartan can be more effective than the
previous antihypertensives, and this is consistent
with the findings by Hasegawa et al.,21 who
switched other ARBs to candesartan on morning
hypertension. Finally, the BP reductions were
more dramatic over the first four weeks, than
over the following weeks (weeks 8 and 12)
for both groups (Table 4 and Figure 2). This
last point, however, seems to be a common
phenomenon for other antihypertensives as well.
Vol 45 • Number 3 • July 2013 Safety and effectiveness of Candesartan and Candesartan/HCT fixed dose
CONCLUSION
Our study showed that candesartan and
candesartan/HCT in clinical daily practice
were well tolerated and effective for treatment-
naïve patients and for long-standing (>4 years)
hypertensive patients uncontrolled with other
antihypertensive medications, including calcium-
channel blockers.
CONFLICT OF INTEREST
The authors received research grant support
from PT. Takeda Indonesia.
ACKNOWLEDGMENTS
We acknowledge PT. Takeda Indonesia for
the financial support for this study. We appreciate
Dr. T. Tanaka from Takeda for reviewing this
manuscript. We thank all physicians who
participated in this study for their contribution
in patient recruitment and data collection.
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