Evaluation of the dose-response relationship of amlodipine and losartan combination in patients with essential hypertension: an 8-week, randomized, double-blind, factorial, phase II, multicenter study.
BACKGROUND
Despite recommendations for more intensive treatment and the availability of several effective treatments, hypertension remains uncontrolled in many patients.


OBJECTIVE
The aim of this study was to determine the dose-response relationship and assess the efficacy and safety of amlodipine or losartan monotherapy and amlodipine camsylate/losartan combination therapy in patients with essential hypertension.


METHODS
This was an 8-week, randomized, double-blind, factorial design, phase II, multicenter study conducted in outpatient hospital clinics among adult patients aged 18-75 years with essential hypertension. At screening, patients received placebo for 2-4 weeks. Eligible patients (n=320) were randomized to one of eight treatment groups: amlodipine 5 mg or 10 mg, losartan 50 mg or 100 mg, amlodipine camsylate/losartan 5 mg/50 mg, 5 mg/100 mg, 10 mg/50 mg, or 10 mg/100 mg.


METHODS
The assumption of strict superiority was estimated using the mean change in sitting diastolic blood pressure (DBP) at 8 weeks. Safety was monitored through physical examinations, vital signs, laboratory test results, ECG, and adverse events.


RESULTS
The reduction in DBP at 8 weeks was significantly greater in patients treated with the combination therapies compared with the respective monotherapies for all specified comparisons except amlodipine camsylate/losartan 10 mg/100 mg versus amlodipine 10 mg. The incidence of adverse events in the group of patients treated with the amlodipine camsylate/losartan 10 mg/50 mg combination tended to be higher than for any other group (27.9%, 12/43); however, the effect was not statistically significant.


CONCLUSIONS
Combination amlodipine camsylate/losartan (5 mg/50 mg, 5 mg/100 mg and 10 mg/50 mg) resulted in significantly greater BP lowering compared with amlodipine or losartan monotherapy, and was determined to be generally safe and tolerable in patients with essential hypertension.


BACKGROUND
Registered at clinicaltrials.gov: NCT00942344.
Department of Cardiology, Korea University Guro Hospital, Catholic Medical Center, Catholic University of Korea, Seoul, Korea.
Chang-Gyu
CG
Park
Ho-Joong
HJ
Youn
Shung-Chull
SC
Chae
Joo-Young
JY
Yang
Moo-Hyun
MH
Kim
Taek-Jong
TJ
Hong
Cheol Ho
CH
Kim
Jae Joong
JJ
Kim
Bum-Kee
BK
Hong
Jin-Won
JW
Jeong
Si-Hoon
SH
Park
Jun
J
Kwan
Young-Jin
YJ
Choi
Seung-Yun
SY
Cho
D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged
D000959:Antihypertensive Agents; D004338:Drug Combinations; D017311:Amlodipine; D019808:Losartan