1
The The SStudy of tudy of TTrandolapril-randolapril-verapamil verapamil AAnd insulin nd insulin RResistance esistance
STAR determined whether glycaemic control was maintained to a STAR determined whether glycaemic control was maintained to a greater degree by an RAS inhibitor/non-DHP CCB than an RAS greater degree by an RAS inhibitor/non-DHP CCB than an RAS
inhibitor/thiazide diuretic in hypertensive patientsinhibitor/thiazide diuretic in hypertensive patientswith metabolic syndromewith metabolic syndrome
2
STAR: rationaleSTAR: rationale
Metabolic syndrome associated with increased risk of Metabolic syndrome associated with increased risk of new-onset diabetes and cardiovascular diseasenew-onset diabetes and cardiovascular disease
Antihypertensive therapy may be beneficial in Antihypertensive therapy may be beneficial in reducing cardiovascular risk in subjects with reducing cardiovascular risk in subjects with metabolic syndromemetabolic syndrome
Certain antihypertensive agents may decrease insulin Certain antihypertensive agents may decrease insulin sensitivity and impair glycaemic controlsensitivity and impair glycaemic control
3
STAR: primary objectiveSTAR: primary objective
To compare the effect of an RAS inhibitor To compare the effect of an RAS inhibitor
combined with a non-dihydropyridine calcium combined with a non-dihydropyridine calcium
channel blocker and an RAS inhibitor channel blocker and an RAS inhibitor
combined with a thiazide diuretic on combined with a thiazide diuretic on
glycaemic control in hypertensive patients glycaemic control in hypertensive patients
with metabolic syndromewith metabolic syndrome
Bakris G, Bakris G, et alet al. . J Clin HypertensJ Clin Hypertens 2006; May(Suppl.). 2006; May(Suppl.).
4
STAR: primary and secondary endpointsSTAR: primary and secondary endpoints
Primary endpointPrimary endpoint
Change from baseline to end of study on 2-hour postprandial Change from baseline to end of study on 2-hour postprandial plasma glucose, using an oral glucose tolerance test (OGTT) plasma glucose, using an oral glucose tolerance test (OGTT)
Secondary endpointsSecondary endpoints
Changes in BP, pulse rate, and BP controlChanges in BP, pulse rate, and BP control
Change in insulin and glucose levelsChange in insulin and glucose levels
Effect on HbAEffect on HbA1c1c levelslevels
Fasting glucose ≥126mg/dl and/or 2-hour OGTT ≥200mg/dlFasting glucose ≥126mg/dl and/or 2-hour OGTT ≥200mg/dl(new-onset diabetes)(new-onset diabetes)
Insulin sensitivity and releaseInsulin sensitivity and release
Albuminuria Albuminuria
Lipid profileLipid profile
Safety profileSafety profileBakris G, Bakris G, et al. J Clin Hypertenset al. J Clin Hypertens 2006; May(Suppl.). 2006; May(Suppl.).Data on file, Abbott Laboratories.Data on file, Abbott Laboratories.
5
STAR: study drugsSTAR: study drugs
Verapamil SRVerapamil SR(non-DHP CCB)(non-DHP CCB)
++
TrandolaprilTrandolapril(ACE inhibitor)(ACE inhibitor)
LosartanLosartan(angiotensin II receptor (angiotensin II receptor
blocker)blocker)
+ +
HydrochlorothiazideHydrochlorothiazide(thiazide diuretic)(thiazide diuretic)
Bakris G, Bakris G, et alet al. . J Clin HypertensJ Clin Hypertens 2006; May(Suppl.). 2006; May(Suppl.).
6
STAR: patients and methodsSTAR: patients and methods
Prospective, randomized, open-label, multicentre design with blinded Prospective, randomized, open-label, multicentre design with blinded outcome evaluation (PROBE) trialoutcome evaluation (PROBE) trialApprox. 30 US study sitesApprox. 30 US study sites240 patients randomized to receive:240 patients randomized to receive:
Verapamil SR/trandolapril (n=119)Verapamil SR/trandolapril (n=119)Losartan/HCTZ (n=121)Losartan/HCTZ (n=121)
52 weeks of treatment52 weeks of treatmentOGTT and lab tests carried out at baseline, week 12, andOGTT and lab tests carried out at baseline, week 12, andweek 52/final visitweek 52/final visitAssumptions:Assumptions:
Baseline 2-hour OGTT mean blood glucose level of 170mg/dlBaseline 2-hour OGTT mean blood glucose level of 170mg/dl(SD ± 25mg/dl) (SD ± 25mg/dl) Type 1 error of 0.05 for two-tailed test Type 1 error of 0.05 for two-tailed test
100 patients per treatment group100 patients per treatment groupProvides 80% power to detect treatment difference of 10mg/dl (6%) inProvides 80% power to detect treatment difference of 10mg/dl (6%) in2-hour OGTT mean change in blood glucose from baseline to end of 2-hour OGTT mean change in blood glucose from baseline to end of study study
Bakris G, Bakris G, et al. J Clin Hypertenset al. J Clin Hypertens 2006; May(Suppl.). 2006; May(Suppl.).Data on file, Abbott Laboratories.Data on file, Abbott Laboratories.
7
STAR: key inclusion criteriaSTAR: key inclusion criteria
Male or female ≥21 years of ageMale or female ≥21 years of age
Metabolic syndrome defined as:Metabolic syndrome defined as:
Fasting blood glucose ≥100-≤125mg/dlFasting blood glucose ≥100-≤125mg/dl
Controlled hypertension on two antihypertensive medicationsControlled hypertension on two antihypertensive medications(SBP <140mmHg) or SBP ≥130 and <160mmHg on monotherapy (SBP <140mmHg) or SBP ≥130 and <160mmHg on monotherapy
Plus at least one of the following criteria:Plus at least one of the following criteria:
HDL-cholesterol <40mg/dl (men) or <50mg/dl (women)HDL-cholesterol <40mg/dl (men) or <50mg/dl (women)
Triglycerides ≥150mg/dlTriglycerides ≥150mg/dl
Waist circumference >40 inches (102cm): men, >35 inchesWaist circumference >40 inches (102cm): men, >35 inches(89cm): women(89cm): women
Female patients could not be pregnant or breast-feedingFemale patients could not be pregnant or breast-feeding
Data on file, Abbott Laboratories.Data on file, Abbott Laboratories.
8
STAR: key exclusion criteriaSTAR: key exclusion criteria
Patients with diabetes or secondary hypertensionPatients with diabetes or secondary hypertension
Those taking more than two antihypertensive agentsThose taking more than two antihypertensive agents
Patients with renal insufficiency (i.e. serum creatinine >1.4mg/dl Patients with renal insufficiency (i.e. serum creatinine >1.4mg/dl and/or urine albumin:creatinine ratio >0.3g/g)and/or urine albumin:creatinine ratio >0.3g/g)
Patients who required the following therapy:Patients who required the following therapy:
NSAIDs or COX-2 inhibitorsNSAIDs or COX-2 inhibitors
Niacin >100mg/dayNiacin >100mg/day
Loop diuretics or multiple diuretics for severe oedemaLoop diuretics or multiple diuretics for severe oedema
Data on file, Abbott Laboratories.Data on file, Abbott Laboratories.
9
STAR: study designSTAR: study design
Bakris G, Bakris G, et al. J Clin Hypertenset al. J Clin Hypertens 2006; May(Suppl.). 2006; May(Suppl.).Data on file, Abbott Laboratories.Data on file, Abbott Laboratories.
*If SBP ≥160 and <180mmHg or DBP ≥100mmHg and <110mmHg 2 weeks after discontinuing antihypertensive *If SBP ≥160 and <180mmHg or DBP ≥100mmHg and <110mmHg 2 weeks after discontinuing antihypertensive therapy, subjects received clonidine 0.1mg bid. Subjects were to discontinue clonidine 2 days prior to baseline. therapy, subjects received clonidine 0.1mg bid. Subjects were to discontinue clonidine 2 days prior to baseline. If SBP ≥180mmHg and/or DBP ≥110mmHg, the subject was withdrawn from the studyIf SBP ≥180mmHg and/or DBP ≥110mmHg, the subject was withdrawn from the study** Uptitration of verapamil SR/trandolapril or losartan/HCTZ for patients not controlled (SBP ≥130mmHg). ** Uptitration of verapamil SR/trandolapril or losartan/HCTZ for patients not controlled (SBP ≥130mmHg). Protocol-allowed additional antihypertensive medications to be added if SBP still ≥130mmHgProtocol-allowed additional antihypertensive medications to be added if SBP still ≥130mmHg*** Six-month extension period where all subjects received verapamil SR/trandolapril was available for all *** Six-month extension period where all subjects received verapamil SR/trandolapril was available for all subjects completing the main studysubjects completing the main study
WeeksWeeks
**
-4-4 44 5252
Verapamil SR/trandolaprilVerapamil SR/trandolapril180/2mg (od)180/2mg (od)
**Verapamil SR/trandolapril **Verapamil SR/trandolapril 180/2mg (od) or 180/2mg (od) or 240/4mg (od)240/4mg (od)
Losartan/HCTZ 50/12.5mg Losartan/HCTZ 50/12.5mg (od)(od) **Losartan/HCTZ 50/12.5 mg **Losartan/HCTZ 50/12.5 mg
(od) or 100/25mg (od)(od) or 100/25mg (od)
Subject Subject screenedscreened
******
******
1212
Washout Washout periodperiod
00
Subject Subject randomizedrandomized End of treatmentEnd of treatment
10
Baseline patient characteristicsBaseline patient characteristics
No significant differences were seen between groups at baselineNo significant differences were seen between groups at baseline
Bakris G, Bakris G, et al. J Clin Hypertenset al. J Clin Hypertens 2006; May(Suppl.). 2006; May(Suppl.).Data on file, Abbott Laboratories.Data on file, Abbott Laboratories.
Characteristic (mean)*Characteristic (mean)*Verapamil Verapamil
SR/trandolaprilSR/trandolapriln=119n=119
Losartan/Losartan/HCTZHCTZn=121n=121
Female gender (%)Female gender (%) 53.853.8 48.848.8
Age (years)Age (years) 57.757.7 55.455.4
Systolic BP (mmHg)Systolic BP (mmHg) 145.4145.4 146.7146.7
Diastolic BP (mmHg)Diastolic BP (mmHg) 86.486.4 88.288.2
Pulse rate (bpm)Pulse rate (bpm) 71.571.5 70.370.3
BMI (kg/mBMI (kg/m22)) 33.833.8 34.634.6
Male waist circumference (cm)Male waist circumference (cm) 112.0112.0 114.0114.0
Female waist circumference (cm)Female waist circumference (cm) 105.0105.0 107.1107.1
**pp=NS=NS
11
3939
No clinically significant difference in office BP No clinically significant difference in office BP at baseline or study end*at baseline or study end*
Bakris G, Bakris G, et al. J Clin Hypertenset al. J Clin Hypertens 2006; May(Suppl.). 2006; May(Suppl.).Data on file, Abbott Laboratories.Data on file, Abbott Laboratories.
*Mean period of follow-up for OGTT was 45.5 weeks for*Mean period of follow-up for OGTT was 45.5 weeks forverapamil SR/trandolapril and 48.3 weeks for losartan/HCTZverapamil SR/trandolapril and 48.3 weeks for losartan/HCTZ
7070
8080
9090
100100
110110
120120
130130
150150
00
Blo
od
pre
ssu
re (
mm
Hg
)B
loo
d p
ress
ure
(m
mH
g)
160160
Mean systolic BPMean systolic BP
Mean diastolic BPMean diastolic BP
End ofEnd ofstudy*study*
Losartan/HCTZLosartan/HCTZ Verapamil SR/trandolaprilVerapamil SR/trandolapril
606022 44 66 88 1212 2626 5252
Verapamil SR/Verapamil SR/trandolapril trandolapril n=n= 119119 116116 115115 113113 113113 112112 100100 9494 9393 119119Losartan/HCTZLosartan/HCTZ n=n= 120120 119119 115115 115115 113113 112112 105105 100100 9797 120120
Time (weeks)Time (weeks)
PP=0.179=0.179
PP=0.605=0.605
140140
12
Proportion of patients with systolic office Proportion of patients with systolic office blood pressure <130mmHg by visitblood pressure <130mmHg by visit
**PP≤0.05; **≤0.05; **PP≤0.01 (between groups)≤0.01 (between groups)
Data on file, Abbott Laboratories.Data on file, Abbott Laboratories.
Verapamil SR/Verapamil SR/trandolapriltrandolapril n=n=119119 116116 115115 113113 113113 112112 100100 9494 9393 119119
Losartan/HCTZ n=Losartan/HCTZ n=120120 119119 115115 115115 113113 112112 105105 100100 9797 120120
BaselineBaseline
% o
f p
atie
nts
% o
f p
atie
nts
6060
4040
2020
00
7070
5050
3030
1010
Week 2Week 2 Week 4Week 4 Week 6Week 6 Week 8Week 8 Week 12Week 12 Week 26Week 26 Week 39Week 39 Week 52Week 52
Losartan/HCTZLosartan/HCTZ
Verapamil SR/trandolaprilVerapamil SR/trandolapril * **
End of End of study***study***
***Mean period of follow-up for OGTT was 45.5 weeks for***Mean period of follow-up for OGTT was 45.5 weeks forverapamil SR/trandolapril and 48.3 weeks for losartan/HCTZverapamil SR/trandolapril and 48.3 weeks for losartan/HCTZ
13Use of concomitantUse of concomitant
antihypertensive medications allowed antihypertensive medications allowed by protocolby protocol
Use of concomitant antihypertensive medications allowed Use of concomitant antihypertensive medications allowed
by protocol to achieve BP goals was similar in both groups by protocol to achieve BP goals was similar in both groups
((PP=0.053 between groups):=0.053 between groups):
56.3% in the verapamil SR/trandolapril group56.3% in the verapamil SR/trandolapril group
43.8% in the losartan/HCTZ group43.8% in the losartan/HCTZ group
Data on file, Abbott Laboratories.Data on file, Abbott Laboratories.
14
Primary endpoint resultPrimary endpoint result
Losartan/HCTZ increased blood plasma glucose significantly more Losartan/HCTZ increased blood plasma glucose significantly more than verapamil SR/trandolapril following OGTT by study end* than verapamil SR/trandolapril following OGTT by study end*
Bakris G, Bakris G, et al. J Clin Hypertenset al. J Clin Hypertens 2006; May(Suppl.). 2006; May(Suppl.).Data on file, Abbott Laboratories.Data on file, Abbott Laboratories.
-10-10
-5-5
00
55
1010
2020
2525
Ch
an
ge
in
blo
od
glu
co
se
at
2 h
ou
rs a
fte
r O
GT
T (
mg
/dl)
Ch
an
ge
in
blo
od
glu
co
se
at
2 h
ou
rs a
fte
r O
GT
T (
mg
/dl)
3030
Losartan/HCTZLosartan/HCTZ
Verapamil SR/trandolaprilVerapamil SR/trandolapril
1515
n=108n=108
n=107n=107
PP<0.001<0.001
Baseline values:Baseline values:Verapamil SR/trandolapril 144mg/dlVerapamil SR/trandolapril 144mg/dlLosartan/HCTZLosartan/HCTZ 142mg/dl 142mg/dl
** Mean period of follow-up for OGTT was Mean period of follow-up for OGTT was 45.5 weeks for verapamil SR/trandolapril 45.5 weeks for verapamil SR/trandolapril
and 48.3 weeks for losartan/HCTZand 48.3 weeks for losartan/HCTZ
15
OGTT results at baseline and study end* OGTT results at baseline and study end*
Significantly greater change in OGTT-glucose AUCSignificantly greater change in OGTT-glucose AUC120120 from baseline to from baseline to study end* with verapamil SR/trandolapril study end* with verapamil SR/trandolapril vv losartan/HCTZ ( losartan/HCTZ (PP=0.003) =0.003)
Data on file, Abbott Laboratories.Data on file, Abbott Laboratories.
** Mean period of follow-up was 45.5 Mean period of follow-up was 45.5 weeks for verapamil SR/trandolapril and weeks for verapamil SR/trandolapril and 48.3 weeks for losartan/HCTZ48.3 weeks for losartan/HCTZ
100100
120120
140140
160160
180180
200200
220220
Mea
n b
loo
d g
luco
se (
mg
/dl)
Mea
n b
loo
d g
luco
se (
mg
/dl)
Time (minutes)Time (minutes)
00 3030 6060 9090 120120
Losartan/HCTZ baselineLosartan/HCTZ baseline
Losartan/HCTZLosartan/HCTZend of study*end of study*
Verapamil SR/trandolaprilVerapamil SR/trandolaprilbaselinebaseline
Verapamil SR/trandolaprilVerapamil SR/trandolaprilend of study*end of study*
16
Requirement for dose titrationRequirement for dose titration
Proportions of patients requiring dose titration for BP Proportions of patients requiring dose titration for BP control were similar in both groups:control were similar in both groups:
76.5% (91/119) in the verapamil SR/trandolapril 76.5% (91/119) in the verapamil SR/trandolapril groupgroup
73.6% (89/121) in the losartan/HCTZ group73.6% (89/121) in the losartan/HCTZ group
Data on file, Abbott Laboratories.Data on file, Abbott Laboratories.
17
Low-dose combinations compared withLow-dose combinations compared withhigh-dose combinationshigh-dose combinations
Data on file, Abbott Laboratories.Data on file, Abbott Laboratories.
-10-10
00
1010
2020
3030
Low doseLow dosethroughout trialthroughout trial
Ch
ang
e in
blo
od
glu
cose
Ch
ang
e in
blo
od
glu
cose
at 2
ho
urs
aft
er O
GT
T (
mg
/dl)
at 2
ho
urs
aft
er O
GT
T (
mg
/dl)
Low doseLow dosetitrated to high dosetitrated to high dose
-20-20
Losartan/HCTZLosartan/HCTZ
Verapamil SR/trandolaprilVerapamil SR/trandolapril
n=85n=85
n=84n=84
n=22n=22
n=24n=24
18
Effect on HbAEffect on HbA1c1c
Bakris G, Bakris G, et al. J Clin Hypertenset al. J Clin Hypertens 2006; May(Suppl.). 2006; May(Suppl.).Data on file, Abbott Laboratories.Data on file, Abbott Laboratories.
Baseline values:Baseline values:Verapamil SR/trandolapril 5.8%Verapamil SR/trandolapril 5.8%Losartan/HCTZLosartan/HCTZ 5.7% 5.7%
** Mean period of follow-up for OGTT was Mean period of follow-up for OGTT was 45.5 weeks for verapamil SR/trandolapril 45.5 weeks for verapamil SR/trandolapril
and 48.3 weeks for losartan/HCTZand 48.3 weeks for losartan/HCTZ
Hb
AH
bA
1c1c (
%)
(%
)
5.55.5
6.56.5
Week 12Week 12 Week 52Week 52
6.06.0Losartan/HCTZLosartan/HCTZ
Verapamil SR/trandolaprilVerapamil SR/trandolapril
n=109n=109
n=97n=97
n=94n=94
PP<0.001<0.001vs baselinevs baseline
PP=0.055=0.055 vs baselinevs baseline
n=112n=112
End of study*End of study*
n=115n=115
n=115n=115
PP=0.027=0.027 vs baselinevs baseline
19
Effect on blood insulin levels Effect on blood insulin levels
Bakris G, Bakris G, et al. J Clin Hypertenset al. J Clin Hypertens 2006; May(Suppl.). 2006; May(Suppl.).Data on file, Abbott Laboratories.Data on file, Abbott Laboratories.
Baseline values:Baseline values:Verapamil SR/trandolapril 112Verapamil SR/trandolapril 112µIµIU/mlU/mlLosartan/HCTZLosartan/HCTZ 106 106µIµIU/mlU/ml** Mean period of follow-up for OGTT was Mean period of follow-up for OGTT was 45.5 weeks for verapamil SR/trandolapril 45.5 weeks for verapamil SR/trandolapril
and 48.3 weeks for losartan/HCTZand 48.3 weeks for losartan/HCTZ
-5-5
00
55
1010
1515
2020
Week 12Week 12
Ch
ang
e in
blo
od
in
suli
nC
han
ge
in b
loo
d i
nsu
lin
at 2
ho
urs
aft
er O
GT
T (
at 2
ho
urs
aft
er O
GT
T (
µIµI U
/ml)
U/m
l)
Week 52Week 52
2525
-10-10
Losartan/HCTZLosartan/HCTZ
Verapamil SR/trandolaprilVerapamil SR/trandolapril
n=100n=100
n=99n=99
n=83n=83
n=86n=86
PP=0.037=0.037
PP=0.014=0.014
End ofEnd ofstudy*study*
n=105n=105
n=102n=102
PP=0.025=0.025
20
Development of new-onset diabetes*Development of new-onset diabetes*
More than three times as many patients in the losartan/HCTZ group More than three times as many patients in the losartan/HCTZ group developed new-onset diabetes at 12 weeks than in the verapamil developed new-onset diabetes at 12 weeks than in the verapamil SR/trandolapril group (using ADA definition)*SR/trandolapril group (using ADA definition)*
Data on file, Abbott Laboratories.Data on file, Abbott Laboratories.
** Fasting blood glucose ≥126mg/dl and/orFasting blood glucose ≥126mg/dl and/or2-hour blood glucose levels after OGTT 2-hour blood glucose levels after OGTT ≥200mg/dl based on ADA definition≥200mg/dl based on ADA definition
**** Mean period of follow-up for OGTT was 45.5 Mean period of follow-up for OGTT was 45.5 weeks for verapamil SR/trandolapril and 48.3 weeks for verapamil SR/trandolapril and 48.3 weeks for losartan/HCTZweeks for losartan/HCTZ
00
55
1010
1515
2020
2525
Week 12Week 12
% o
f p
atie
nts
% o
f p
atie
nts
Week 52Week 52
3030
Losartan/HCTZLosartan/HCTZ
Verapamil SR/trandolaprilVerapamil SR/trandolapril
6/866/86
20/9320/93
10/7210/72
20/8320/83PP=0.007=0.007
PP=0.048=0.048
End ofEnd ofstudy**study**
10/9110/91
25/9425/94
PP=0.002=0.002
21
Incidence of treatment-emergent adverse Incidence of treatment-emergent adverse events occurring in 5% or more of patientsevents occurring in 5% or more of patients
Overall incidence of treatment-emergent adverse events was similar Overall incidence of treatment-emergent adverse events was similar in both treatment groupsin both treatment groups
Adverse event Adverse event
Number (% of patients)Number (% of patients)
P P valuevalueVerapamil SR/Verapamil SR/trandolapril (n = 119)trandolapril (n = 119)
Losartan/HCTZLosartan/HCTZ(n= 121)(n= 121)
ConstipationConstipation 11 (9%)11 (9%) 4 (3%)4 (3%) NSNS
CoughCough 7 (6%)7 (6%) 1 (1%)1 (1%) 0.0350.035
Diabetes mellitusDiabetes mellitus 10 (8%)10 (8%) 16 (13%)16 (13%) NSNS
Dizziness Dizziness 9 (8%)9 (8%) 5 (4%)5 (4%) NSNS
Dry mouthDry mouth 8 (7%)8 (7%) 7 (6%)7 (6%) NSNS
FatigueFatigue 6 (5%)6 (5%) 7 (6%)7 (6%) NSNS
HeadacheHeadache 6 (5%)6 (5%) 5 (4%)5 (4%) NSNS
Pain in extremityPain in extremity 6 (5%)6 (5%) 00 0.0140.014
SinusitisSinusitis 6 (5%)6 (5%) 3 (2%)3 (2%) NSNS
Upper respiratory tract infectionUpper respiratory tract infection 7 (6%)7 (6%) 6 (5%)6 (5%) NSNS
Urinary tract infectionUrinary tract infection 6 (5%)6 (5%) 6 (5%)6 (5%) NSNS
Data on file, Abbott Laboratories.Data on file, Abbott Laboratories.
22
The STAR trial: summaryThe STAR trial: summary
STAR compared the effect of an RAS inhibitor/non-DHP CCBSTAR compared the effect of an RAS inhibitor/non-DHP CCBand an RAS inhibitor/thiazide diuretic on glycaemic control in and an RAS inhibitor/thiazide diuretic on glycaemic control in hypertensive patients with metabolic syndromehypertensive patients with metabolic syndrome
Little or no change in glucose tolerance was demonstrated with Little or no change in glucose tolerance was demonstrated with verapamil SR/trandolapril, whereas glucose levels (2-hour OGTT), verapamil SR/trandolapril, whereas glucose levels (2-hour OGTT), HbAHbA1c,1c, and insulin levels were significantly increased with and insulin levels were significantly increased with losartan/HCTZlosartan/HCTZ
Significantly higher incidence of new-onset diabetes was seen in Significantly higher incidence of new-onset diabetes was seen in losartan/HCTZ group (using ADA definition)losartan/HCTZ group (using ADA definition)
Blood pressure was significantly reduced with bothBlood pressure was significantly reduced with bothcombination treatmentscombination treatments
Overall safety profiles were comparable between groupsOverall safety profiles were comparable between groups
Bakris G, Bakris G, et al. J Clin Hypertenset al. J Clin Hypertens 2006; May(Suppl.). 2006; May(Suppl.).Data on file, Abbott Laboratories.Data on file, Abbott Laboratories.