ALLHAT Antihypertensive Trial Results by Baseline Diabetic

1
ALLHAT Antihypertensive Trial Results by Baseline
Diabetic Fasting Glucose Status
2
Introduction and Background

• Clinical trials have reported reduction in CV
  events with diuretics, CCBs, ACE inhibitors,
  b-blockers, and ARBs.
• JNC7 guidelines indicate all these classes are
  acceptable.
• Nevertheless, concerns have been raised regarding
  effects of some classes in diabetic patients.

3
Major Outcomes in High Risk Hypertensive Patients
Randomized to Angiotensin-Converting Enzyme
Inhibitor or Calcium Channel Blocker vs Diuretic

• The Antihypertensive and Lipid-Lowering Treatment
  to Prevent Heart Attack Trial (ALLHAT)

The ALLHAT Collaborative Research Group Sponsored
by the National Heart, Lung, and Blood Institute
(NHLBI)
www.allhat.org JAMA 20022882981-2997
4
Introduction and Background

• 15,297 ALLHAT participants had diabetes (by
  history) at baseline.
• This represents 36 of the study cohort.
• Clearly makes ALLHAT the largest antihypertensive
  drug comparison trial in hypertensive diabetic
  patients.

5
Randomized Design of ALLHAT BP Trial
High-risk hypertensive patients
Consent / Randomize
Amlodipine Lisinopril Doxazosin Chlorthalidone
Follow for CHD and other outcomes until death or
end of study (up to 8 yr mean 4.9 yrs).
6
Participants with DM in AHT Drug Trials
7
Results Based OnDiabetes by History Only JAMA
20022882981-2997
8
Biochemical Results Fasting Glucose mg/dL
plt.05 compared to chlorthalidone
JAMA 20022882981-2997
9
Diabetes Incidence - 4 Years(follow-up FBS ? 126
mg/dL for those lt126 mg/dL at baseline)


plt.05 compared to chlorthalidone
JAMA 20022882981-2997
10
Diabetics Nondiabetics (History)Amlodipine/Chlo
rthalidone
Relative Risk and 95 Confidence Intervals
Favors Favors Amlodipine
Chlorthal
JAMA 20022882981-2997
11
Diabetics Nondiabetics (History)Lisinopril/Chlo
rthalidone
Relative Risk and 95 Confidence Intervals
Favors
Favors Lisinopril
Chlorthal
JAMA 20022882981-2997
12
Results Based OnDiabetes by History and Baseline
Glucose Measurements Arch Intern Med.
20051651401-1409
13
Diabetes by History Baseline Fasting Glucose
14
Diabetes by History Baseline Fasting Glucose
15
Diabetes by History and Baseline Fasting Glucose
by Treatment Group
16
Baseline Characteristics Diabetic, IFG, and
Nondiabetic Participants
Randomized to chlorthalidone, amlodipine, or
lisinopril plt.05 compared to nondiabetic
participants
17
Blood Pressure at 5 Years -Diabetic, Impaired
Fasting Glucose, and Nondiabetic Participants
18
CHD in Participants with a History of Diabetes
Mellitus or with FG 126 at Baseline
.2
.16
Chlorthalidone Amlodipine Lisinopril
.12
Cumulative CHD Event Rate
.08
.04
0
0
1
2
3
4
5
6
7
Years to CHD Event
19
CHD in Participants With Impaired Fasting
Glucose (No History of Diabetes)
.2
.16
Chlorthalidone Amlodipine Lisinopril
.12
Cumulative CHD Event Rate
.08
.04
0
0
1
2
3
4
5
6
7
Years to CHD Event
20
CHD in Normoglycemic Participants (No History of
Diabetes)
.2
.16
.12
Cumulative CHD Event Rate
Chlorthalidone Amlodipine Lisinopril
.08
.04
0
0
1
2
3
4
5
6
7
Years to CHD Event
21
Diabetes-Treatment Interactions - CHD
22
Outcomes in the Blood Pressure Component of ALLHAT
DIABETIC GROUP
Favors Favors Amlodipine
Chlorthalidone
Favors Favors Lisinopril
Chlorthalidone
23
Outcomes in the Blood Pressure Component of ALLHAT

Favors
Favors Amlodipine
Chlorthalidone
Favors Favors Lisinopril
Chlorthalidone
24
Outcomes in the Blood Pressure Component of ALLHAT

Favors Favors Amlodipine
Chlorthalidone
Favors Favors Lisinopril
Chlorthalidone
25
Diabetes-Treatment Interactions - CCHD
26
Race-Diabetes-Treatment Interactions
27
ALLHAT Results by Baseline Diabetic Status
Summary

• Treatment group comparison results for CVD and
  ESRD events were similar in diabetic and
  nondiabetic participants.
• Compared with chlorthalidone arm
• Higher risk of HF with amlodipine
• Higher risk of stroke, HF, and combined CVD with
  lisinopril

28
ALLHAT Results by Baseline Diabetic Status
Summary (cont)

• Results for CVD and ESRD events were also similar
  in small group of participants with IFG, except
  for possible excess CHD with amlodipine
• Post-hoc sub-group
• May merit further study

29
ALLHAT Results by Baseline Diabetic Status
Implications

• For minimizing CVD/renal risk in medium term,
  thiazide-like diuretics preferred, except
• ALLHAT did not address proteinuric nephropathy.
• Do differences in glycemia translate into
  long-term advantage for CVD/renal events?
• Not for CVD death, based on SHEP extended
  follow-up analyses post-trial ALLHAT FU
  continues.
• Ongoing trials testing glycemia-reduction?CVD

30
The conclusions presented for the ALLHAT diabetes
subgroups are entirely consistent with the
overall conclusions for the entire study cohort.
31
EXTRA SLIDES
32
All-Cause Mortality in Participants with a
History of Diabetes Mellitus or FG 126 mg/dL at
Baseline
33
All-Cause Mortality in Participants with Impaired
Fasting Glucose (No History of Diabetes)
.28
.24
.2
.16
Chlorthalidone Amlodipine Lisinopril
Cumulative Mortality Rate
.12
.08
.04
0
0
1
2
3
4
5
6
7
Years to Death
34
All-Cause Mortality in Normoglycemic
Participants (No History of Diabetes)

Chlorthalidone
Amlodipine
Lisinopril
0
1
2
3
4
5
6
7
Years to Death
35
Combined CHD in Participants with a History of
Diabetes Mellitus or FG 126 mg/dL at Baseline
.3
.2
Chlorthalidone Amlodipine Lisinopril
Cumulative Combined CHD Event Rate
.1
0
0
1
2
3
4
5
6
7
Years to Combined CHD Event
36
Combined CHD in Participants with Impaired
Fasting Glucose (No History of Diabetes)
.3
.2
Chlorthalidone Amlodipine Lisinopril
Cumulative Combined CHD Event Rate
.1
0
0
1
2
3
4
5
6
7
Years to Combined CHD Event
37
Combined CHD in Normoglycemic Participants (No
History of Diabetes)
.3
.2
Chlorthalidone Amlodipine Lisinopril
Cumulative Combined CHD Event Rate
.1
0
0
1
2
3
4
5
6
7
Years to Combined CHD Event
38
Stroke in Participants with a History of Diabetes
Mellitus or with FG 126 mg/dL at Baseline
39
Stroke in Participants with Impaired Fasting
Glucose (No History of Diabetes)
.12
.08
Chlorthalidone Amlodipine Lisinopril
Cumulative Stroke Rate
.04
0
0
1
2
3
4
5
6
7
Years to Stroke
40
Stroke in Normoglycemic Participants (No History
of Diabetes)
.12
.08
Chlorthalidone Amlodipine Lisinopril
Cumulative Stroke Rate
.04
0
0
1
2
3
4
5
6
7
Years to Stroke
41
Stroke by Race by Baseline Diabetic Status
Amlodipine / Chlorthalidone
42
Stroke by Race by Baseline Diabetic Status
Lisinopril / Chlorthalidone
43
Heart Failure in Participants with a History of
Diabetes Mellitus or with FG 126 mg/dL at
Baseline
.2
.16
Chlorthalidone Amlodipine Lisinopril
.12
Cumulative HF Rate
.08
.04
0
0
1
2
3
4
5
6
7
Years to HF
44
Heart Failure in Participants with Impaired
Fasting Glucose (No History of Diabetes)
.2
.16
Chlorthalidone Amlodipine Lisinopril
.12
Cumulative HF Rate
.08
.04
0
0
1
2
3
4
5
6
7
Years to HF
45
Heart Failure in Normoglycemic Participants (No
History of Diabetes)
.2
.16
Chlorthalidone Amlodipine Lisinopril
.12
Cumulative CHF Rate
.08
.04
0
0
1
2
3
4
5
6
7
Years to CHF
46
Combined CVD in Participants with a History of
Diabetes Mellitus or with FG 126 mg/dL at
Baseline
.45
.3
Cumulative Combined CVD Event Rate
Chlorthalidone Amlodipine Lisinopril
.15
0
0
1
2
3
4
5
6
7
Years to Combined CVD Event
47
Combined CVD in Participants with Impaired
Fasting Glucose (No History of Diabetes)
.45
.3
Cumulative Combined CVD Event Rate
Chlorthalidone Amlodipine Lisinopril
.15
0
0
1
2
3
4
5
6
7
Years to Combined CVD Event
48
Combined CVD in Normoglycemic Participants (No
History of Diabetes)
.45
.3
Chlorthalidone Amlodipine Lisinopril
Cumulative Combined CVD Event Rate
.15
0
0
1
2
3
4
5
6
7
Years to Combined CVD Event
49
ESRD in Participants with a History of Diabetes
Mellitus or with FG 126 mg/dL at Baseline
50
ESRD in Participants with Impaired Fasting
Glucose (No History of Diabetes)
.04
.03
Chlorthalidone Amlodipine Lisinopril
.02
Cumulative ESRD Rate
.01
0
0
1
2
3
4
5
6
7
Years to ESRD
51
ESRD in Normoglycemic Participants (No History of
Diabetes)
.04
.03
Chlorthalidone Amlodipine Lisinopril
.02
Cumulative ESRD Rate
.01
0
0
1
2
3
4
5
6
7
Years to ESRD