Transcript How were step-up drugs selected and used in ALLHAT?

How were step-up drugs selected
and used in ALLHAT?
ALLHAT Step-up Drugs: General
Considerations
• Avoided drugs of blinded first-step classes
(unless compelling indications), so as not to
confound first step-comparisons
• Drugs provided by study all had different
mechanisms than first-step drugs, i.e. 3
antiadrenergics, 1 direct vasodilator
• Other drugs at investigators’ discretion, not
paid for by ALLHAT
Of participants taking blinded drug,
% on step-up drugs
ALLHAT Step-up Drugs: Patterns
of Use by Arm at One Year*
30
25
20
Chlor
Amlod
Lisin
15
10
5
0
Atenolol
Reserpine
Clonidine
*Refers to addition of step-up drugs to blinded drugs
Hydrazaline
ALLHAT Step-up Drugs: Patterns
of Use by Arm at Three Years*
30
25
20
Chlor
Amlod
Lisin
15
10
5
0
Atenolol
Reserpine
Clonidine
*Refers to addition of step-up drugs to blinded drugs
Hydralazine
Of participants taking blinded drug,
% on step-up drugs
ALLHAT Step-up Drugs: Patterns
of Use by Arm at Five Years*
35
30
25
Chlor
Amlod
Lisin
20
15
10
5
0
Atenolol
Reserpine
Clonidine
Hydralazine
*Refers to addition of step-up drugs to blinded drugs
ALLHAT Step-up/Open-Label Drugs:
Number Used by Arm at One Year
40
35
30
25
20
15
10
5
0
Participants Assigned
to Treatment Arm
Participants Taking
Step 1 Drug
C:
C:
C:
A:
A:
A:
L:
L:
L:
1 SUD
2 SUD
3+ SUD
1 SUD
2 SUD
3+ SUD
1 SUD
2 SUD
3+ SUD
SUD=step-up or
open-label drugs
ALLHAT Step-up/Open-Label Drugs:
Number Used by Arm at Three Years
40
C:
C:
C:
A:
A:
A:
L:
L:
L:
35
30
25
20
15
10
5
1 SUD
2 SUD
3+ SUD
1 SUD
2 SUD
3+ SUD
1 SUD
2 SUD
3+ SUD
0
Participants Assigned to
Treatment Arm
Participants Taking Step 1
Drug
SUD=step-up or
open-label drugs
ALLHAT Step-up/Open-Label Drugs:
Number Used by Arm at Five Years
45
40
35
30
25
20
15
10
5
0
Participants Assigned
to Treatment Arm
Participants Taking
Step 1 Drug
C:
C:
C:
A:
A:
A:
L:
L:
L:
1 SUD
2 SUD
3+ SUD
1 SUD
2 SUD
3+ SUD
1 SUD
2 SUD
3+ SUD
SUD=step-up or
open-label drugs
Open-Label Therapy: Patterns of Use by
Arm at One Year by Participants Taking
Step 1 Drug
Of those taking blinded
drug, % on OL therapy
8
7
6
Diuretic
CCB
ACE-I
Other OLT*
5
4
3
2
1
0
Chlorthalidone
Arm
Amlodipine
Arm
Lisinopril
Arm
*Other OLT refers to meds other than the step 1 classes or the step 2-3 drugs
Of those taking blinded
drug, % on OL therapy
Open-Label Therapy: Patterns of Use by
Arm at Three Years by Participants Taking
Step 1 Drug
14
12
10
Diuretic
CCB
ACE-I
Other OLT*
8
6
4
2
0
Chlorthalidone
Arm
Amlodipine
Arm
Lisinopril
Arm
*Other OLT refers to meds other than the step 1 classes or the step 2-3 drugs
Open-Label Therapy: Patterns of Use by
Arm at Five Years by Participants Taking
Step 1 Drug
20
18
16
14
12
10
8
6
4
2
0
Chlorthalidone
Arm
Diuretic
CCB
ACE-I
Other OLT*
Amlodipine
Arm
Lisinopril
Arm
*Other OLT refers to meds other than the step 1 classes or the step 2-3 drugs
Conclusions
• Although distribution of specific add-on drugs
was generally similar across randomized
groups, more drugs were consistently added
in the lisinipril group.
• The greater use of add-on drugs, especially
clonidine and hydralazine, may reflect the
lesser blood pressure lowering of lisinopril (in
the absence of a diuretic or CCB).
Conclusions
(continued)
• The greater use of open-label diuretics in the
amlodipine and lisinopril groups may have led
to underestimating the outcome differences
between the groups.
• Given the lesser need for adding drugs to
diuretics for BP lowering, and in the absence
of advantages for CVD or renal outcomes for
ACE-I, ALLHAT results suggest little
justification for ACE-I to be preferred over
diuretics as initial therapy.