Phase IV, 8-Week, Multicenter, Randomized, Active
Treatment–Controlled, Parallel Group, Efficacy, and
Tolerability Study of High-Dose Candesartan Cilexetil
Combined With Hydrochlorothiazide in Korean Adults With
Stage II Hypertension
Hae-Young Lee, MD
1
; Bum-Kee Hong, MD
2
; Wook Jin Chung, MD
3
;
Byoung Kwon Lee, MD
2
; Seung Hwan Lee, MD
4
; Dong Woon Jeon, MD
5
;
Young Keun Ahn, MD
6
; Dooil Kim, MD
7
; Chang Kyu Park
8
; Sang-Hyun Kim, MD
9
;
Hae Ok Jung, MD
10
; Byung-Ok Kim, MD, PhD
11
; and Donghoon Choi, MD
12
1
Seoul National University Hospital, Seoul, Republic of Korea;
2
Gangnam Severance Hospital, Seoul, Republic of
Korea;
3
Gachon University Gil Hospital, Incheon, Republic of Korea;
4
Yonsei University Wonju Hospital,
Wonju, Republic of Korea;
5
National Health Insurance Corporation Ilsan Hospital, Goyang-si, Republic of
Korea;
6
Chonnam National University Hospital, Gwangju, Republic of Korea;
7
Inje University Busan-Paik
Hospital, Busan, Republic of Korea;
8
Korea University Guro Hospital, Seoul, Republic of Korea;
9
Boramae
Hospital, Seoul, Republic of Korea;
10
The Catholic University of Korea, Seoul, St. Mary’s Hospital, Seoul,
Republic of Korea;
11
Inje University Sanggye Paik Hospital, Seoul, Republic of Korea; and
12
Yonsei University
Severance Hospital, Seoul, Republic of Korea
ABSTRACT
Objective: The objective of this study was to evalu-
ate the efficacy and tolerability of high-dose (32 mg)
candesartan in Asians.
Methods: In Korean adult patients with stage II hy-
pertension, we evaluated the efficacy and tolerability of
candesartan 16 mg/hydrochlorothiazide (HCT) 12.5
mg and candesartan 32 mg/HCT 12.5 mg compared
with candesartan 16-mg and 32-mg monotherapy, re-
spectively. This Phase IV, 8-week, multicenter, ran-
domized, active treatment– controlled, parallel group,
efficacy, and tolerability study, named CAESAR (Can-
desartan Effect in Second Stage Arterial Hyperten-
sion), enrolled 253 patients with stage II hypertension.
Treatment started with either candesartan 16 mg or
candesartan 16 mg/HCT 12.5 mg. After 4 weeks, the
candesartan dose was forced titrated to 32 mg in both
groups. The primary and secondary objectives were to
compare the blood pressure (BP) changes after 4 weeks
and 8 weeks between candesartan-HCT combination
therapy and candesartan monotherapy. The propor-
tion of patients achieving target BP (systolic blood
pressure [SBP] Ͻ140 mm Hg, but Ͻ130 mm Hg for
patients with diabetes mellitus or chronic kidney disease;
diastolic blood pressure (DBP) Ͻ90 mm Hg, but Ͻ80
mm Hg for those with diabetes mellitus or chronic kidney
disease) after 4 and 8 weeks of therapy was also evalu-
ated. Adverse events were investigated both by spontane-
ous report by the patient and by the investigators’ evalu-
ations in each visit. Laboratory tests were performed at
the end of the study to evaluate drug tolerability.
Results: Study patients were all Asians, mostly male
(65.7%), with a mean (SD) age of 49.4 (10.6) years and
a mean body weight of 68.9 (12.1) kg; there were no
between-group variances in demographic profiles ex-
cept that the mean age in the candesartan-HCT group
(51.0 [10.2] years) was about 3.2 years higher than
that in the candesartan monotherapy group (47.8
[10.7] years; P ϭ 0.02) despite random allocation. A
total of 80.4% of the study patients had not been
treated before, whereas 19.6% were previously treated
and enrolled after 2 weeks of washout period. Baseline
sitting systolic/diastolic BPs (SBP/DBP) were 160.7
(13.0)/104.6 (9.5) mm Hg. After 4 weeks, patients
H.-Y. Lee and B.-K. Hong have equally contributed to this work.
Accepted for publication June 30, 2011.
doi:10.1016/j.clinthera.2011.07.002
0149-2918/$ - see front matter
© 2011 Elsevier HS Journals, Inc. All rights reserved.
Clinical Therapeutics/Volume 33, Number 8, 2011
August 2011 1043