ORIGINAL PAPER
Evaluation of Blood Pressure Reduction Response and Responder
Characteristics to Fixed-Dose Combination Treatment of Amlodipine and
Losartan: A Post Hoc Analysis of Pooled Clinical Trials
Sreevalsa Unniachan, MPH;1,2 David Wu, PhD;1 Srinivasan Rajagopalan, PhD;3 Mary E. Hanson, PhD;1 Kenji P.Fujita, MD1
Merck & Co. Inc., Whitehouse Station, NJ;1 Rutgers School of Public Health, Piscataway, NJ;2 and Med Data Analytics, Milltown, NJ
Data from four clinical trials compared reductions in systolic
blood pressure (SBP) and diastolic blood pressure (DBP)
among patients treated with amlodipine/losartan 5/50 mg vs
5/100 mg and amlodipine/losartan 5/50 mg vs amlodipine
5 mg and 10 mg. Response rate was assessed as reduction
in SBP or DBP (>20/10 mm Hg) and proportion of patients
achieving SBP <140 mm Hg or DBP <90 mm Hg. Patients
were grouped into quartiles based on baseline SBP and
DBP. Mean SBP and DBP were reduced in amlodipine/
losartan 5/50 mg (n=182) and amlodipine/losartan 5/100 mg
(n=95) users across all baseline quartiles. Patients using
amlodipine/losartan 5/50 mg had significantly greater SBP
Hypertension is an important modifiable risk factor for
cardiovascular disease.1 Hypertension accounts for the
greatest mortality burden, accounting for more than
7 million deaths worldwide, more than any other
known risk factor.2 Moreover, mortality from stroke
and ischemic heart disease doubles for every 20 mm Hg
increase in systolic blood pressure (SBP) and every 10
mm Hg increase in diastolic blood pressure (DBP).3 It is
estimated that if hypertension control were optimized,
cardiac mortality would decline by 49% and cerebro-
vascular mortality by 62%.4
Hypertension contributes to a high global disease
burden and is as prevalent in developing countries as in
developed countries.5 Approximately one third of the
world’s burden of hypertension-attributable cardiovas-
cular disease is estimated to occur in East Asia, Pacific,
Latin American, and Caribbean countries.6 Despite an
increasing prevalence and awareness of hypertension
and significant advances in effective treatment options,
blood pressure (BP) control remains suboptimal.7
Moreover, compared with Western countries, BP con-
trol in Asian countries is still far from optimum.8
It is now recognized that treatment with a single
antihypertensive agent, regardless of class, achieves
the recommended BP target of 140/90 mm Hg in less
than half of all patients.9,10 The Seventh Report of the
Joint National Committee on Prevention, Detection,
Address for correspondence: David Wu, PhD, Global Health Outcomes,
Merck & Co., Inc., One Merck Drive, WS2E47, Whitehouse Station, NJ
08889
E-mail: wei.wu@merck.com
Manuscript received: April 1, 2014; revised: July 10, 2014; accepted:
July 13, 2014
DOI: 10.1111/jch.12390
3
and DBP reductions vs amlodipine 5 mg (P=.001 and P=.02,
respectively). Amlodipine/losartan 5/50 mg users had sig-
nificantly greater SBP reduction vs amlodipine 10 mg (SBP
P=.02; DBP P=not significant). The odds of responding to
therapy were significantly greater with amlodipine/losartan
5/50 mg vs amlodipine 5 mg (odds ratio, 5.33; 95%
confidence interval, 1.42–25.5) and were similar vs amlod-
ipine 10 mg (odds ratio, 0.67; 95% confidence interval,
0.017–9.51). These results support the use of combination
therapy early in the treatment of hypertension. J Clin
Hypertens (Greenwich). 2014;16:671–677. ª 2014 Wiley
Periodicals, Inc.
Evaluation, and Treatment of High Blood Pressure
(JNC 7) guidelines state that more than two thirds of
hypertensive individuals will require more than one
antihypertensive agent from different drug classes to
achieve their BP targets (<140/90 mm Hg, or <130/80
mm Hg for patients with diabetes or chronic kidney
disease).11 Treatment guidelines recommend that a
combination of agents or fixed-dose combinations
(FDCs) be used to initiate therapy in patients with
SBP/DBP >20/10 mm Hg above their goal or in those
at high risk for cardiovascular complications or as an
escalation for patients not controlled on monotherapy.
FDC therapy offers beneficial BP-lowering effects
while minimizing the adverse effects potentially related
to the titration of each agent administered individually
as monotherapy.12 By improving medication adherence,
FDCs improve BP goal attainment, which, in turn,
translates to better clinical outcomes.13 In addition,
combination therapy has other advantages in terms of
renoprotective effects other than controlling hyperten-
sion and reducing side effects caused by their synergistic
actions.14–16
COZAAR XQ (Merck & Co., Inc. Whitehouse
Station, NJ) is an FDC therapy of amlodipine (5 mg,
10 mg) and losartan (50 mg, 100 mg) for the treatment
of essential hypertension. Clinical trials have consis-
tently shown that this FDC has resulted in significantly
greater BP reduction compared with amlodipine or
losartan monotherapy among patients with both essen-
tial hypertension and stage 2 hypertension.17–19 Losar-
tan and amlodipine are frequently used as first-line
therapies in hypertensive patients,20,21 and other studies
have also outlined the benefits of combining these two
drugs.22
The Journal of Clinical Hypertension Vol 16 | No 9 | September 2014 671
Evaluation of BP Reduction BP Response | Unniachan et al.
To further examine the antihypertensive efficacy and
to understand the factors associated with BP target
response, we conducted this secondary analysis of
pooled amlodipine/losartan clinical trial data. The
objectives of this study were (1) to examine the
relationship between BP reduction among amlodipine/
losartan 5/50 mg and 5/100 mg users and their baseline
SBP and DBP status, (2) to examine the differences in
patient response rate to therapy between starting dose of
amlodipine/losartan (5/50 mg) and trial comparator
(amlodipine 5 mg, 10 mg), and (3) to examine the
differences in 8-week mean BP change from baseline in
patients treated with amlodipine/losartan (5/50 mg) in
comparison with trial comparators.
METHODS
Study Design
Data were pooled from four randomized, double-blind,
clinical trials (three phase III and one phase II) that
included essential hypertensive patients treated with
amlodipine/losartan (HM-ALOS-201 [clinicaltrials.gov:
NCT00942344]; HM-ALOS-301 [ClinicalTrials.gov:
NCT00940667; HM-ALOS-302 [ClinicalTrials.
gov: NCT00940680], HM-ALOS-303 [ClinicalTri-
als.gov: NCT01127217]).17–19,23 In all studies, patients
provided written informed consent, and study protocols
were approved by the appropriate local ethical review
boards of each study site.
To assess the overall mean change from baseline in
DBP and SBP after 8 weeks among patients treated with
amlodipine/losartan 5/50 mg and 5/100 mg, data from
all four trials were combined. To compare the response
rate and change from baseline in BP after 8 weeks of
treatment with amlodipine/losartan 5/50 mg vs amlod-
ipine 5 or 10 mg, data were pooled from two trials
(HM-ALOS-201 and HM-ALOS-303).19,23 Two trials
(HM-ALOS-301 and HM-ALOS-302) were excluded
from the analysis because one (HM-ALOS-301) was an
amlodipine 5 mg nonresponder study and the other
(HM-ALOS-302) did not include amlodipine/losartan
(5/50 mg) and amlodipine (5, 10 mg).
Patients
The analysis population included patients 18 years or
older with essential hypertension (HM-ALOS-303 lim-
ited to stage II hypertension patients). The baseline
demographics were generally similar between the study
populations included in the four trials. Mean age was
50 to 55 years, the majority of participants were men
(72–81%), and body weight ranged from 68 kg to
72 kg. Mean baseline SBP ranged from 144 mm Hg to
170 mm Hg and mean DBP ranged from 97 mm Hg to
103 mm Hg. All four studies were randomized,
double-blind, multicenter trials conducted in Korea.
Three of the four studies were 8-week phase III trials
with 1:1 randomization of two treatment groups (HM-
ALOS-301, conducted from May to September 2008;
HM-ALOS-302, conducted from April to November
672 The Journal of Clinical Hypertension Vol 16 | No 9 | September 2014
2008; and HM-ALOS-303 conducted May 2009 to
March 2010). One study was an 8-week, phase II trial
(HM-ALOS-201, conducted from May through
December of 2007) with a block randomization code
for eight treatment groups (1:1:1:1:1:1:1:1). Before
randomization, any prior treatments with antihyper-
tensive drugs were discontinued in all participants.
Patients were excluded if the dose was titrated from
amlodipine 5 mg to amlodipine 10 mg by week 2 or
week 6 of the study HM-ALOS-303. Other exclusion
criteria were applied according to the exclusion criteria
of the individual trials. Patients included in these
analyses were maintained on the same dose regimen
(amlodipine/losartan 5/50 mg, 5/100 mg, amlodipine
5 mg, or amlodipine 10 mg) for 8 weeks after any run-
in during the trials.
Measures
Throughout the trials, all patients had their BP
measured three times at each visit using a mercury
sphygmomanometer and the mean value was used. The
mean change from baseline in SBP and DBP and
response rate were measured and compared between
amlodipine users and combination therapy users.
Responders were defined as patients with >20 mm
Hg reduction from baseline in SBP or >10 mm Hg
reduction from baseline in DBP at 8 weeks or having
achieved a BP goal of SBP <140 mm Hg or DBP <90
mm Hg at 8 weeks.
Statistical Analysis
Patients who had no protocol violations, received at
least one dose of study medication (including the control
medication), and had valid 8-week BP measures were
included in the analysis. Descriptive and univariate
statistics were used to analyze patient profiles and
treatment effect on patient responder rates and BP
reduction across treatment arms. The patients were
classified into quartiles based on baseline SBP and DBP
separately for both doses of amlodipine/losartan use to
assess change in BP across each of the arms. The quartile
ranges corresponded to Q1: below 25th percentile; Q2:
25th to 50th percentile; Q3: 50th to 75th percentile; and
Q4: above 75th percentile of the corresponding baseline
SBP and DBP values for each of the amlodipine/losartan.
Chi-square tests were used for categorical data and t
tests and analysis of variance were used for continuous
variables. Data are reported as mean and standard
deviation (SD) for continuous variables and percentage
for categorical variables. Two-sided P values <.05 were
considered significant. Multivariate logistic regression,
adjusted for covariates including age, sex, height,
weight, baseline SBP, baseline DBP, smoking status,
drinking status, history of cardiovascular comorbidities,
and history of antihypertensive medications was per-
formed to compare treatment effect on patient respon-
der rates across treatment arms, reported as odds ratios
and P values. All analyses were performed using SAS
version 9.2 (SAS Institute Inc, Cary, NC).
 Evaluation of BP Reduction BP Response | Unniachan et al.

RESULTS 109.85 mm Hg in Q4. In patients treated with amlod-

Across the four studies, a total of 182 patients were
treated with amlodipine/losartan 5/50 mg and 95
patients were treated with amlodipine/losartan 5/
100 mg (Table). The mean age of patients treated with
amlodipine/losartan 5/50 mg was 55 years (SD=9.51)
and were predominantly men (74.7%). This was similar
in the amlodipine/losartan 5/100 group (mean age,
53 years; 70.5% men). Mean BMI was similar for both
amlodipine/losartan 5/50 mg (25.8; SD=3.16) and 5/
100 mg (25.8; SD=3.24) users. Amlodipine/losartan 5/
50 users had an average baseline SBP of 155 (SD=16.9)
mm Hg and DBP of 100 (SD=7.4) mm Hg. Amlodipine/
losartan 5/100 users had a slightly lower baseline SBP of
146 mm Hg (SD=15.2) and DBP of 98 mm Hg
(SD=6.7). Compared with the amlodipine/losartan 5/
100 mg users, patients in the amlodipine/losartan 5/
50 mg group had a higher proportion of current
smokers (5/50 mg: 24.24%, 5/100 mg: 18.9%) and
patients with alcohol consumption (5/50 mg: 70.3%, 5/
100 mg: 62.1%).
Within the amlodipine/losartan 5/50 mg group, with
a baseline SBP range of 123 mm Hg to 199 mm Hg, the
quartile limits corresponded to 140 mm Hg for 25th
percentile, 159.65 mm Hg for 50th percentile, and 166
mm Hg for 75th percentile. The mean baseline SBP by
quartile was 133.98 mm Hg in quartile 1 (Q1), 147.02
mm Hg in quartile 2 (Q2), 162.39 mm Hg in quartile 3
(Q3), and 175.2 mm Hg in quartile 4 (Q4). Similarly,
the mean DBP at baseline by quartile was 91.38 mm Hg
in Q1, 96.21 mm Hg in Q2, 100.45 mm Hg in Q3, and
ipine/losartan 5/100 mg, mean baseline SBP by quartile
was 133.41 mm Hg in Q1, 142.85 mm Hg in Q2,
147.72 mm Hg mm Hg in Q3, and 156.74 mm Hg in
Q4 and baseline mean DBP by quartile was 94.08 mm
Hg in Q1, 95.9 mm Hg in Q2, 98.7 mm Hg in Q3, and
103.57 mm Hg in Q4.
At week 8, the mean change in BP among patients
treated with amlodipine/losartan 5/50 mg based on
quartiles is shown in Figure 1. Patients in Q4 experi-
enced a mean change in DBP of 18.3 mm Hg, while
patients in Q1 experienced a mean change in DBP of
8.28 mm Hg. The differences in the mean change in SBP
between quartiles were Q4= 37.14, Q3= 32.46,
Q2= 14.6, and Q1= 9.81 mm Hg.
Quartile limits for amlodipine/losartan 5/100 mg
patients corresponded to a minimum value of 110 mm
Hg, 25th percentile of 136.7 mm Hg, 50th percentile of
146 mm Hg, 75th percentile of 154 mm Hg, and a
maximum value of 198.7 mm Hg. Similarly, quartile
cutoffs for baseline DBP corresponded to a minimum
value of 92.7 mm Hg, 25th percentile of 92.7 mm Hg,
50th percentile of 97.3 mm Hg, 75th percentile of 101.3
mm Hg, and a maximum value of 116.7 mm Hg.
Figure 2 shows the change in BP among patients treated
with amlodipine/losartan 5/100 mg for all quartiles. In
patients treated with amlodipine/losartan 5/100 mg,
mean changes by quartiles in SBP were 9.49 mm Hg
in Q1, 10.82 mm Hg in Q2, 18.69 mm Hg in Q3,
and 27.69 mm Hg in Q4, and mean changes by
quartile in DBP were 10.33 mm Hg in Q1, 11.63

TABLE. Baseline Patient Characteristics

Amlodipine 5 mg Amlodipine 5 mg
and Losartan 50 mg and Losartan 100 mg Amlodipine 5 mg Amlodipine 10 mg
Variable, Mean (SD) or No. (%) (n=182) (n=95) (n=57) (n=32)

Age 54.98 (9.51) 52.63 (9.13) 54.84 (9.03) 55.53 (9.66)

Male 136 (74.73) 67 (70.53) 37 (64.91) 21 (65.63)
BMI 25.79 (3.16) 25.81 (3.24) 24.91 (2.34) 26.13 (2.77)
Baseline SBP 155.00 (16.89) 146.05 (15.02) 157.03 (14.76) 153.04 (12.9)
Baseline DBP 99.93 (7.40) 98.29 (6.68) 100.67 (5.99) 100.40 (4.55)
Current smoking status 45 (24.73) 18 (18.95) 8 (14.04) 4 (12.5)
History of smoking 84 (46.15) 47 (49.47) 23 (40.35) 15 (46.88)
Current alcohol consumption 128 (70.33) 59 (62.11) 34 (59.65) 22 (68.75)
History of alcohol consumption 137 (75.27) 64 (67.37) 37 (64.91) 25 (78.13)
Medical historya 40 (21.98) 24 (25.26) 19 (33.33) 5 (15.63)
Cardiovascular 8 (4.40) 3 (3.16) 2 (3.51) 0
Cerebrovascular 1 (0.55) 2 (2.11) 1 (1.75) 0
Diabetes 7 (3.85) 2 (2.11) 3 (5.26) 2 (6.25)
Dyslipidimia 14 (7.69) 16 (16.84) 10 (17.54) 2 (6.25)
Renal 13 (7.14) 3 (3.16) 6 (10.53) 2 (6.25)
History of medication 116 (63.74) 64 (67.37) 34 (59.56) 18 (56.25)
Antidiabetics 3 (1.65) 1 (1.05) 1 (1.75) 2 (6.25)
Concurrent comorbiditya 33 (18.13) 21 (22.11) 18 (31.58) 4 (12.5)
History of hypertension treatment 109 (59.89) 59 (62.11) 32 (56.14) 18 (56.25)
Abbreviations: BMI, body mass index; DBP, diastolic blood pressure; SBP, systolic blood pressure; SD, standard deviation.
a
Concurrent comorbidity included any one with one or more of the conditions such as cardiovascular and cerebrovascular comorbidity, diabetes,
dyslipidemia, and renal conditions.

The Journal of Clinical Hypertension Vol 16 | No 9 | September 2014 673

Evaluation of BP Reduction BP Response | Unniachan et al.

Baseline sitDBP Quartile (mean mmHg) Baseline sitSBP Quartile (mean mmHg)
Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4
(91.38) (96.21) (100.45) (109.85) (133.98) (147.02) (162.39) (175.20)
(n=44) (n=37) (n=52) (n=49) (n=45) (n=46) (n=41) (n=50)
0 0

-10
-9.81
sitDBP Change (mmHg)

sitSBP Change (mmHg)

-5
-14.60
-20
-8.28
-10
-30
-12.03
-32.46
-13.47
-15
-40 -37.14

-18.30
-20 -50

FIGURE 1. Blood pressure reduction with amlodipine/losartan 5/50 mg categorized based on baseline systolic blood pressure (SBP) and
diastolic blood pressure (DBP) into quartiles.

Baseline sitDBP Quartile (mean mmHg) Baseline sitSBP Quartile (mean mmHg)
Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4
(90.86) (94.82) (99.03) (107.45) (128.19) (140.68) (149.99) (164.58)
(n=23) (n=22) (n=25) (n=25) (n=23) (n=24) (n=24) (n=24)
0 0

-5
sitSBP Change (mmHg)
sitDBP Change (mmHg)

-5
-10
-9.49
-10.82
-10 -15
-10.33
-11.63
-12.67 -20 -18.69
-15
-15.80 -25

-30 -27.69
-20

FIGURE 2. Blood pressure reduction with amlodipine/losartan 5/100 mg categorized based on baseline systolic blood pressure (SBP) and
diastolic blood pressure (DBP) into quartiles.

mm Hg in Q2, 12.67 mm Hg in Q3, and 15.80 mm (93.9% vs 80.7%; P=.0297). At 8 weeks, patients
Hg in Q4. The mean reduction in SBP and DBP was treated with amlodipine/losartan also experienced a
greater in patients in the higher quartile compared with significantly greater reduction in SBP compared with
those in the lower quartile. patients treated with amlodipine 5 mg (30.94 vs 22.08,
A total of 155 patients (amlodipine/losartan: n=66; P=.001). Similarly, patients treated with amlodipine/
amlodipine 5 mg: n=57; amlodipine 10 mg: n=32) were losartan experienced a significantly greater reduction in
included in the responder analysis pooled from the DBP compared with patients treated with amlodipine
trials. Figure 3 shows the proportion of patients treated 5 mg (15.73 vs 12.24, P=.02; Figure 4).
with amlodipine/losartan who achieved BP response Patients treated with amlodipine/losartan and amlod-
compared with those who treated with amlodipine 5 mg ipine 10 mg both experienced a positive response rate
monotherapy. Significantly more patients treated with (93.94% vs 96.88%), but this difference was not
amlodipine/losartan 5/50 mg achieved a positive statistically significant (Figure 5). Figure 6 shows the
response compared with amlodipine 5 mg patients mean change from baseline in BP with amlodipine/

674 The Journal of Clinical Hypertension Vol 16 | No 9 | September 2014

 Evaluation of BP Reduction BP Response | Unniachan et al.

Responder Responder
100% 100% 96.88%
93.94% 93.94%
95% 95%

90% 90%
85%
85%
80.70%
80%
80%
75%
75% P=.0297 p=NS
70%
70%
65%
65%
60%
60%
55%
55%
50%
50% COZAAR XQ ® 5/50 mg Amlodipine 10 mg
COZAAR XQ ® 5/50 mg Amlodipine 5 mg NS: not significant
(N=66) (N=57)

FIGURE 5. Proportion of patients achieving blood pressure

FIGURE 3. Proportion of patients achieving blood pressure
response: amlodipine/losartan 5/50 mg vs amlodipine 5 mg
monotherapy.
losartan 5/50 mg vs amlodipine 10 mg monotherapy.
At 8 weeks of therapy, treatment with amlodipine/
losartan resulted in a significantly greater reduction in
SBP compared with amlodipine 10 mg (30.94 mm Hg
vs 24.71 mm Hg, P=.02) while the reduction in DBP
response with amlodipine/losartan 5/50 mg vs amlodipine 10 mg.
was similar between the two groups (15.73 mm Hg vs
16.54 mm Hg, P=not significant).
Multivariate logistic regression adjusted for covariates
such as age, sex, height, weight, baseline SBP, baseline
DBP, smoking status, drinking status, history of cardio-
vascular comorbidities, and history of antihypertensive

SBP Reduction at 8 Weeks DBP Reduction at 8 Weeks

From Baseline From Baseline
COZAAR XQ ® Amlodipine COZAAR XQ ® Amlodipine
5/50 mg 5 mg 5/50 mg 5 mg
0

-5

P=.001 P=.02
-10

-12.24
-15
(8.19)
-15.73
-20 (8.34)

-22.08
-25
(15.54)

-30
-30.94
-35 (14.20)

FIGURE 4. Mean blood pressure reduction amlodipine/losartan 5/50 mg vs amlodipine 5 mg monotherapy after 8 weeks. SBP indicates
systolic blood pressure; DBP, diastolic blood pressure.

The Journal of Clinical Hypertension Vol 16 | No 9 | September 2014 675

Evaluation of BP Reduction BP Response | Unniachan et al.
SBP Reduction at 8 Weeks
From Baseline
COZAAR XQ ®
5/50 mg
0
-5
P =.02
-10
-15
-20
-25
-30
-30.94
-35 (14.20)
FIGURE 6. Mean blood pressure reduction with amlodipine/losartan 5/50 mg vs amlodipine 10 mg monotherapy at 8 weeks. SBP indicates
systolic blood pressure; DBP, diastolic blood pressure; NS, not signficant.
use shows that the odds of response to therapy were
significantly greater for patients treated with amlodi-
pine/losartan 5/50 mg compared with amlodipine 5 mg
(adjusted OR, 5.33; 95% CI, 1.42–25.5). When com-
pared with amlodipine 10 mg, patients treated with
amlodipine/losartan 5/50 mg had similar odds of
response to therapy (adjusted OR, 0.67; 95% CI,
0.017–9.51).
DISCUSSION
In this pooled study, we found that patients who took
amlodipine/losartan 5/50 mg and 5/100 mg showed a
consistent reduction in BP across all quartiles of SBP and
DBP. The results show a trend towards greater reduc-
tion among patients with higher baseline SBP and DBP.
Patients taking amlodipine/losartan 5/50 mg also had a
greater rate of BP goal attainment at 8 weeks of
treatment compared with those taking amlodipine
10 mg. A large majority (>90%) of uncontrolled
hypertension patients responded to the starting dose of
amlodipine/losartan (5/50 mg) treatment, with a signif-
icantly higher odds of response to the therapy vs the
starting dose of amlodipine (5 mg) monotherapy, with a
similar odds of response to therapy vs maximum dose
amlodipine (10 mg) monotherapy. The starting dose of
amlodipine/losartan (5/50 mg) showed greater reduc-
tions in both 8-week mean SBP and DBP from baseline
compared with amlodipine 5 mg. When compared with
the maximum dose of amlodipine (10 mg), amlodipine/
676 The Journal of Clinical Hypertension Vol 16 | No 9 | September 2014
DBP Reduction at 8 Weeks
From Baseline
Amlodipine COZAAR XQ ® Amlodipine
10 mg 5/50 mg 10 mg
P =NS
-15.73
-16.54
(8.34)
(7.84)
-24.71
(11.08)
losartan 5/50 mg significantly improved 8-week mean
SBP reduction but had similar 8-week mean DBP
reduction from baseline.
The association between higher baseline BP and
increased BP reduction as well as the higher proportion
of patients reaching BP goal with amlodipine/losartan
FDC provides a representation of the clinical profiles of
patients who might benefit from amlodipine/losartan
FDC. These findings support guidelines (eg, JNC 7 and
European Society of Cardiology) that advocate early
initiation with combination therapy consisting of two
antihypertensive drugs with complementary mecha-
nisms of action.11
Several combination therapies are shown to be
effective in hypertension. Calcium channel blockers
and angiotensin-converting enzyme (ACE) inhibitors
have long been considered effective.24 However, their
use may be limited in some patients because of the
associated higher incidence of side effects compared
with angiotensin receptor blockers (ARBs). Conse-
quently, more studies of calcium channel blockers and
ARBs have been initiated and proven equally effective as
their component monotherapies.25–27 Although the use
of antihypertensive combination therapy has increased
substantially in recent years, such therapies are still
underutilized.28 FDCs have been associated with
improved patient adherence and fewer safety and
tolerability issues and have been proven cost-effective
compared with their monotherapy components.29

STUDY LIMITATIONS
A few limitations to be addressed for this study are that
the trials included in the analysis were conducted in
Korean populations and therefore may limit generaliz-
ability to other populations. This may be ameliorated to
a certain degree since, unlike ACE inhibitors, ARBs
have not been reported to have differences in response
to BP reduction based on ethnicity. One study in the
analysis was limited to patients with stage 2 hyperten-
sion, whereas the others included all patients with
essential hypertension. Although this may not be a
source of bias due to the randomized design, it is worth
mentioning. Our population was generally younger
(mean age of 55 years) compared with many trials;
therefore, selection bias may be a concern and calls for a
larger study in a more diverse population.
CONCLUSIONS
The results of this study demonstrated that patients
treated with amlodipine/losartan showed significant
reductions in BP compared with patients treated with
amlodipine alone. In addition, patients treated with dual
therapy had a better responder rate for BP reduction
compared with patients treated with monotherapy. Our
findings support the recommendations of JNC 7 guide-
lines for management of hypertension, which suggest
the use of combination therapy early in the treatment of
hypertension.
Acknowledgments and disclosures: Merck & Co., Inc., Whitehouse Station,
NJ, provided financial support for the conduct of the study. Editorial
assistance was provided by Jennifer Rotonda, PhD, of Merck & Co., Inc. SU
is a research fellow at Merck & Co., Inc. DW, MEH, and KPF are employees of
Merck & Co., Inc. and may own stock or hold stock options in the company.
SR reports personal fees from Merck & Co., Inc. and from Bristol Myers
Squibb Inc. outside the submitted work.
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