ALLHAT
Success and Predictors of Blood Pressure
Control in Diverse North American
Settings: The Antihypertensive and Lipidlowering Treatment to Prevent Heart
Attack Trial (ALLHAT)
William C Cushman, MD, Charles E Ford, PhD,
Jeffrey A Cutler, MD, Karen L Margolis, MD, MPH,
Barry R Davis, MD, PhD, et al, for the
ALLHAT Collaborative Research Group
J Clinical Hypertens 2002; 4:393-404
Blood Pressure Control (<140/90 mm Hg)
Rates in The United States in the 1990s
z NHANES III:
¾ 27% for adults with hypertension.
¾ Among those on treatment in NHANES III:
30 to 45% in older adults from various sexrace/ethnicity groups.
z In treated patients in Olmstead County, MN:
¾ 33% among persons 45 years and older.
z At a group of New England Veterans Affairs
Medical Centers:
¾ < 25% in older (mostly white) males
Burt, et al. Hypertension 1995;25:305-13.
Meissner, et al. Hypertension 1999;34:466-71.
Berlowitz, et alN Engl J Med 1998;339:1957-63.
ALLHAT
42,418
High-risk
hypertensive
patients
Randomized Design
of ALLHAT BP Trial
Consent /
Randomize
Amlodipine
Chlorthalidone
Doxazosin
Lisinopril
Follow until death or end of study (4-8 years, mean 4.9 years)
ALLHAT
Inclusion Criteria
z Men and women aged > 55 years
z Seated blood pressure (2 categories):
1) Treated for @ least 2 months.
2) Not on drugs or on drugs < 2 months.
z Additional risk factor or target organ
damage.
ALLHAT
ALLHAT BP Eligibility
Criteria
Lower Limit
(mm Hg)
Upper Limit
(mm Hg)
SBP
DBP
SBP
DBP
Visit 1
---
---
160
100
Visit 2
---
---
180
110
140
90
180
110
Status at Visit 1 and Visit 2
On 1-2 drugs used
for hypertension
>= 2 months
On drugs for < 2
Visit 1 &
months or
Visit 2
currently untreated
SBP or DBP lower limit must be met at Visit 1 and Visit 2
SBP and DBP upper limit must be met at Visit 1 and Visit 2
ALLHAT Baseline Characteristics
Sample Size
33,357
Mean SBP/DBP
145 / 83
Mean age, years
67
Black, %
Women, %
35
47
Current smoking %
22
ASCVD, %
Type II diabetes, %
47
36
LVH by ECG, %
3
Mean BMI, kg/m2
30
ALLHAT
Baseline Characteristics
Serum Creatinine, mg/dL
1.02
Fasting Glucose, mg/dL
125
Total Cholesterol, mg/dL
216
LDL-Cholesterol, mg/dL
HDL-Cholesterol, mg/dL
136
47
Triglycerides, mg/dL
172
Antihypertensive
Treatment
ALLHAT
Regimen
Step 1
Chlorthalidone
Dose 1
Dose 2
Dose 3
12.5 mg
12.5 mg
25 mg
Amlodipine
2.5 mg
5 mg
10 mg
Lisinopril
10 mg
20 mg
40 mg
Reserpine
0.05 mg qd
0.1 mg qd
0.2 mg qd
Clonidine
0.1 mg bid
0.2 mg bid
0.3 mg bid
Atenolol
25 mg qd
50 mg qd
100 mg qd
25 mg bid
50 mg bid
100 mg bid
Step 2
Step 3
Hydralazine
Mean
Systolic
and
Diastolic
ALLHAT
Blood Pressure
150
145
145
Systolic BP
140
140
135 ~
mm Hg
90 ~
83
85
81
138
137
136
135
135
77
76
75
36
48
60
Diastolic BP
79
80
78
75
70
0
12
24
Months of Follow-up
Cushman, et al. J Clinical Hypertens 2002; 4:393-404
BP Results by Treatment Group
Chlorthalidone
150
mm Hg BP
145
Amlodipine
Lisinopril
BL
6M
1Y
3Y
5Y
C
146.2
138.2
136.6
134.6
134.1
A
146.2
140.0
138.3
135.4
134.9
L
146.4
141.4
139.7
136.4
136.1
140
90
85
m m Hg BP
ALLHAT
75
130
70
1
2
3
Years
4
5
6
Compared to chlorthalidone:
SBP significantly higher in the
amlodipine group (~1 mm Hg) and
the lisinopril group (~2 mm Hg).
6M
1Y
3Y
5Y
C
84.0
80.1
79.2
77.1
75.4
A
83.9
79.7
78.5
76.1
74.5
L
84.1
80.8
79.7
77.2
75.4
80
135
0
BL
0
1
2
3
4
5
Years
Compared to chlorthalidone:
6
DBP significantly lower in the
amlodipine group (~1 mm Hg).
JAMA 2002;288:2981-2997
ALLHAT SBP Distribution at Baseline
and 36 Months of Follow-up
40
Percent
30
Baseline:
31% < 140 mm Hg
14% ≥ 160 mm Hg
36 Months:
64% < 140 mm Hg
8% ≥ 160 mm Hg
20
10
0
<100 100- 110- 120- 130- 140- 150- 160- 170- 180+
109 119 129 139 149 159 169 179
SBP (mm Hg)
Cushman, et al. J Clinical Hypertens 2002; 4:393-404
ALLHAT DBP Distribution at Baseline
and 36 Months of Follow-up
30
Percent
20
Baseline
68% < 90 mm Hg
4% ≥ 100 mm Hg
36 Months
90% < 90 mm Hg
2% ≥ 100 mm Hg
10
0
<65
6569
7074
7579
8084
8589
9094
9599
100- 105+
104
DBP (mm Hg)
Cushman, et al. J Clinical Hypertens 2002; 4:393-404
Blood Pressure Control
Blood Pressure Control
ALLHAT
DBP<90
100
Percent
80
68%
60
40
88%
86%
58
31
SBP<140
55
BP<140/90
90%
60 58
64 62
2
3
91%
67 65
92%
67 66
27
20
0
0
1
4
5
Years of Follow-up
Cushman, et al. J Clinical Hypertens 2002; 4:393-404
ALLHAT
SBP Distribution at 36
Months of Follow-up
64% < 140 mm Hg
36% ≥ 140 mm Hg
8% ≥ 160 mm Hg
Of those ≥ 140 mm Hg:
53% 140-149 mm Hg
24% 150-159 mm Hg
(77% 140-159 mm Hg)
40
31.5
Percent
30
20.9
20
9.1
10
0.5
19
8.5
4.6
2.4
1.9
1.6
0
<100 100- 110- 120- 130- 140- 150- 160- 170- 180+
109 119 129 139 149 159 169 179
SBP (mm Hg)
Cushman, et al. J Clinical Hypertens 2002; 4:393-404
BP Control (<140/90 mm Hg) at 5
Years by Randomized Group
80
68
66
61
Percent
60
40
20
0
Chlorthalidone
Amlodipine
Lisinopril
JAMA 2002;288:2981-2997
ALLHAT
Blood Pressure Control
1.6
DBP<90
100
Percent
80
86%
68%
60
40
31 27
58 55
1.4
= mean number of drugs
SBP<140
88%
60 58
BP<140/90
90%
64 62
91%
67 65
1.6
1.7
1.8
2
3
4
92%
67 66
2.0
20
0
0
1
5
Years of Follow-up
Cushman, et al. J Clinical Hypertens 2002; 4:393-404
ALLHAT
Use of Blinded (Step 1) Drug and
Number of Antihypertensive Drugs
Prescribed
100
On Step 1 Drug
Percent
80
On 1 Drug
60
40
On 2 Drugs
20
On 3 Drugs
On 4+ Drugs
0
0
12
24
36
48
60
Months of Follow-Up
@ 5 years: 62% were on >2 drugs, 30% were
on 1 drug with BP <140/90 mm Hg
Cushman, et al. J Clinical Hypertens 2002; 4:393-404
Proportion of Uncontrolled
ALLHAT Participants Not
Stepped Up at Annual Visits
80
Percent
60
68
69
72
72
2
3
4
5
59
40
20
0
1
Years
Cushman, et al. J Clinical Hypertens 2002; 4:393-404
ALLHAT
Multiple Logistic Regression Analysis:
Relative Odds (95% CI) of BP Control
at 36 Months
Baseline SBP (10 mmHg ↑) *
Age (10 year ↑) g
Male *
Black g
Type 2 Diabetic
Smoker g
ASCVD *
BMI ≥ 30 kg/m2 *
Prior Rx *
Cr ≥ 1.5 mg/dL *
ECG LVH *
Clinic Research Exp. *
0.5
0.6
0.7
0.8
0.9
BP Control Worse
More (*) or less (g) likely to be on 2+ drugs
1
1.1
1.2
BP Control Better
Cushman, et al. J Clinical Hypertens 2002; 4:393-404
ALLHAT
Logistic Regression Analysis of
Relative Odds (95% CI) of Being On
2+ Drugs at 36 Months
Baseline SBP (10 mmHg ↑)
Age (10 year ↑)
Male
Black
Type 2 Diabetic
Smoker
ASCVD
BMI ≥ 30 kg/m2
Prior Rx
Cr ≥ 1.5 mg/dL
ECG LVH
Clinic Research Exp.
0.7
0.9
Less Likely To Be
On 2+ Drugs
1.1
1.3
1.5
1.7
1.9
2.1
2.3
More Likely To Be On 2+ Drugs
Cushman, et al. J Clinical Hypertens 2002; 4:393-404
Relative Odds (95% CI) of BP Control or Being
On 2+ Drugs at 36 Months of Follow-Up, by
Geographic Region (Compared with West)
ALLHAT
BP Control Worse
BP Control Better
East
Midwest
South
Canada
Puerto Rico/VI
Less Likely To Be On 2+ Drugs
East
Midwest
South
Canada
Puerto
Rico/VI
0.2
0.4
0.6
0.8
More Likely To Be On 2+ Drugs
1
1.2
1.4
1.6
1.8
2
Cushman, et al. J Clinical Hypertens 2002; 4:393-404
Other Large Trials and BP
Control
z LIFE (4.8 years of f/u):
¾ 46%: atenolol arm
¾ 49%: losartan arm
z CONVINCE (30 and 36 months
of f/u):
¾ 67% overall and similar in
verapamil HS and standard
therapy arms
ALLHAT
Conclusions - 1
z The ALLHAT trial provides compelling
evidence that BP control rates can be
markedly increased to at least 2/3 of the
treated hypertensive population.
z These control rates were achieved in a
multiethnic hypertensive population in
diverse practice settings.
z Most of the participants who did not
achieve goal had persistent elevation of
SBP.
ALLHAT
Conclusions - 2
z At least 2 antihypertensive medications are
required for most patients to achieve BP
control.
z Various factors that are associated with
lower BP control rates were identified.
z It is likely that the majority of people with
hypertension could achieve BP < 140/90
mm Hg with the antihypertensive
medications available today.
BP Inadequately Controlled† in Nearly 75%
of Adult Hypertensives* in the US
NHANES II
1976-1980
NHANES III
(Phase 1)
1988-1991
Aware
51%
73%
68%
Treated
31%
55%
54%
10%
29%
27%
†
Controlled
NHANES III
(Phase 2)
1991-1994
† SBP <140 mm Hg and DBP <90 mm Hg.
NHANES = National Health and Nutrition Examination Surveys.
•Age 18 to 74 years with SBP 140 mm Hg or DBP 90 mm Hg or taking antihypertensive medication.
JNC VI. Arch Intern Med. 1997;157:2413-46.
26
ALLHAT
ALLHAT
n=42,418
• Participants were randomized to chlorthalidone
(15,255), amlodipine (9,048), lisinopril (9,054), or
doxazosin (9,061) between 2/94-1/98.
[Sponsored by NHLBI]
• Over 15,000 (>3000/drug group) of ALLHAT
participants had DM at baseline and a similar #
were African Americans.
• The doxazosin arm was stopped in January 2000
due to higher CV events and virtually no chance to
show a difference in CHD.
• The remaining 3 arms continued to scheduled
completion and were reported in December 2002.
ALLHAT
Inclusion Criteria - 2
At least one of the following:
•
•
•
•
•
•
•
•
Myocardial infarction or stroke: age-indeterminate
or at least 6 months old
History of revascularization procedure
Other documented ASCVD
Major ST segment depression or T-wave inversion
Type II diabetes mellitus
HDL cholesterol < 35 mg/dl on any 2 or more
determinations in past 5 years
Left ventricular hypertrophy (past 2 years) on ECG
or echo
Current cigarette smoking
ALLHAT
Exclusion Criteria for
Antihypertensive Trial
z Angina pectoris or recent MI or Stroke (within past 6
months)
z Heart failure and/or LVEF < 35%, if known
z Renal insufficiency (serum creatinine > 2.0 mg/dL)
z Requiring diuretics, calcium channel blockers, ACE
inhibitors, or alpha adrenergic blockers for reasons
other than high blood pressure
z Requiring more than two antihypertensive agents to
achieve blood pressure control
z Factors suggesting inability to comply with protocol
ALLHAT
Number of Antihypertensive
Drugs Used and BP Control
(<140/90 mm Hg)
2.5
80
1.3
60
40
20
50%
1.4
55%
1.6
58%
1.7
62%
1.8
65%
2
2
66%
1.5
1
0.5
27%
0
Number of Drugs
% <140/90 mm Hg
100
0
0
6
12
24
Months
36
48
60
Cushman, et al. J Clinical Hypertens 2002; 4:393-404