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ALLHAT. U.S. Department of Health and Human Services. National Institutes of Health. National Heart, Lung, and Blood Institute. Cardiovascular Outcomes in Hypertensives with CHD Randomized to Amlodipine versus Lisinopril in ALLHAT. - PowerPoint PPT Presentation
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Cardiovascular Outcomes in Hypertensives with CHD Randomized
to Amlodipine versus Lisinopril in ALLHAT
Frans Leenen MD, PhD, Chuke Nwachuku MA, MPH, Dr PH, William Cushman MD, Henry Black MD, Lara Simpson MS,
Barry Davis MD, PhD.
For the ALLHAT Collaborative Research Group
Sponsored by the National Heart, Lung and Blood Institute (NHLBI) in collaboration with the Department of Veterans Affairs
U.S. Department of Health and Human
Services
National Institutes of Health
National Heart, Lung, and Blood Institute
ALLHATALLHAT
www.allhat.org
BackgroundBackgroundALLHATALLHAT
* In the 90’s several mainly observational studies reported unfavorable cardiovascular outcomes on therapy with DHP-CCB’s in patients with CHD.
* Placebo-controlled RCT’s such as HOPE or EUROPA (but not PEACE) concluded that (hypertensive) patients with CHD show benefits from ACE-inhibitor therapy beyond that expected from BP lowering per se.
on the other hand:
Objective of Present Post-Hoc AnalysisObjective of Present Post-Hoc Analysis
ALLHATALLHAT
Comparison of cardiovascular and other outcomes among 18,102 patients with or without CHD at baseline randomized to the ACE-inhibitor lisinopril or the DHP-CCB amlodipine.
42,418 high-riskhypertensive patients
90% previously treated10% untreated
STEP 1 AGENTSSTEP 1 AGENTS
Chlorthalidone12.5-25 mg
Amlodipine2.5-10 mg
Lisinopril10-40 mg
Doxazosin1-8 mg
N=15,255 N=9,048 N=9,054 N=9,061
STEP 2 AND 3 AGENTS (5 years)STEP 2 AND 3 AGENTS (5 years)
Atenolol28.0%
Clonidine10.6%
Reserpine4.3%
Hydralazine10.9%
Hypertension TrialALLHATALLHAT
CHD at BaselineALLHATALLHAT
“known prior MI, angina, primary cardiac
arrest, coronary artery stenosis >50%,
reversible perfusion defect, or major
coronary revascularization procedure”
Baseline Characteristics by CHD at Baseline
CHD at Baseline No CHD at Baseline
Aml(n=2202)
Lis(n=2270)
Aml(n=6777)
Lis(n=6715)
SBP/DBP, mean 145/83 146/83 147/84 147/84
Age in yrs, mean 67.9 68.1 66.6 66.4
On antihypertensive meds (%) 93 92 90 90
Type 2 diabetes (%) 26 27 40 38
Cigarette smoker (%) 15 15 24 24
Female (%) 36 34 51 50
Blacks (%) 24 24 39 39
On aspirin (%) 60 59 29 28
ALLHATALLHAT
74
76
78
80
82
84
86
1.92.0
1.91.7
Y3
1.81.8
1.81.6
Y2 Y4 Y1BLMean # of Meds:
1.71.6
1.51.5
1.71.5
1.51.3
Amlodipine CHD at BLNo CHD at BL
Lisinopril CHD at BLNo CHD at BL
mm
Hg
BP
Δ =1.1
Δ =1.5
Δ =1.0Δ =1.1
132
134
136
138
140
142
144
146
148
Amlodipine - CHD at BL
Amlodipine - No CHD at BL
Lisinopril - CHD at BLLisinopril - No CHD at BL
mm
Hg
BP
Δ =1.5
Δ =0.8
Δ =1.8
Δ =1.2
Baseline and Follow-up BPs by CHD at BLALLHAT
Events – L vs. ARelative Risk and 95% Confidence Intervals
Favors Lisinopril Favors Amlodipine
0.50 1 2
PAD 1.19 (1.01-1.40)
Revascularization 1.00 (0.91-1.11)
Angina 1.09 (1.00-1.19)
HF 0.87 (0.78-0.96)
GI Bleed 1.20 (1.06-1.37)
Cancer 1.01 (0.91-1.12)
ESRD 0.99 (0.77-1.26)
Combined CVD 1.06 (1.00-1.12)
Stroke 1.23 (1.08-1.41)
Combined CHD 1.04 (0.97-1.12)
Death 1.05 (0.97-1.13)
CHD 1.01 (0.91-1.11)
ALLHAT
p=0.047
p=0.045
Cumulative Event Rates for Primary Endpoint by CHD at Baseline and
Treatment GroupALLHAT
0.00
0.05
0.10
0.15
0.20
0 1 2 3 4 5 6 7
Years to Primary Endpoint
AmlodipineLisinopril
No CHD at BL
0.00
0.05
0.10
0.15
0.20
Cu
mu
lati
ve
CH
D R
ate
0 1 2 3 4 5 6 7
Years to Primary Endpoint
AmlodipineLisinopril
CHD at BL
RR (95%CI) P value
L/A 1.15 (0.99-1.32) 0.06
RR (95%CI) P value
L/A 0.99 (0.88-1.13) 0.92
Secondary Endpoints:Lisinopril versus Amlodipine ALLHAT
CHD at BL No CHD at BL
RR (95% CI) P value RR (95% CI) P value
Combined CHD 1.07 (0.96-1.20) 0.24 1.02 (0.93-1.12) 0.64
All-Cause Mortality 1.15 (0.99-1.32) 0.06 1.01 (0.92-1.11) 0.78
ESRD 0.92 (0.54-1.56) 0.75 1.00 (0.76-1.32) 0.99
Cumulative Event Rates for Stroke by CHD at Baseline and Treatment GroupALLHAT
RR (95%CI) P value
L/A 1.31 (1.01-1.69) 0.04
RR (95%CI) P value
L/A 1.20 (1.02-1.41) 0.03
0.00
0.05
0.10
0 1 2 3 4 5 6 7
Years to Stroke
AmlodipineLisinopril
No CHD at BL
Cu
mu
lati
ve
Ss
tro
ke
Ra
te
0.00
0.05
0.10
0 1 2 3 4 5 6 7
Years to Stroke
AmlodipineLisinopril
CHD at BL
Cumulative Event Rates for Heart Failure by CHD at Baseline and
Treatment GroupALLHAT
RR (95%CI) P value
L/A 0.91 (0.76-1.09) 0.31
RR (95%CI) P value
L/A 0.85 (0.74-0.97) 0.02
0.00
0.05
0.10
0.15
0.20
0 1 2 3 4 5 6 7
Years to HF
AmlodipineLisinopril
No CHD at BL
0.00
0.05
0.10
0.15
0.20
Cu
mu
lati
ve
HF
Ra
te
0 1 2 3 4 5 6 7
Years to HF
AmlodipineLisinopril
CHD at BL
Cumulative Event Rates for Angina by CHD at Baseline and
Treatment GroupALLHAT
RR (95%CI) P value
L/A 0.99 (0.87-1.12) 0.87
RR (95%CI) P value
L/A 1.17 (1.03-1.32) 0.02
0.00
0.05
0.10
0.15
0.20
0.25
0 1 2 3 4 5 6 7
Years to Angina
AmlodipineLisinopril
No CHD at BL
0.00
0.05
0.10
0.15
0.20
0.25
Cu
mu
lati
ve
AN
G R
ate
0 1 2 3 4 5 6 7
Years to Angina
AmlodipineLisinopril
CHD at BL
Cumulative Event Rates for PAD by CHD at Baseline and Treatment GroupALLHAT
RR (95%CI) P value
L/A 0.93 (0.71-1.21) 0.58
RR (95%CI) P value
L/A 1.39 (1.12-1.71) 0.002
0.00
0.05
0.10
Cu
mu
lati
ve
PA
D R
ate
0 1 2 3 4 5 6 7
Years to PAD
AmlodipineLisinopril
CHD at BL
0.00
0.05
0.10
0 1 2 3 4 5 6 7
Years to PAD
AmlodipineLisinopril
No CHD at BL
Combined CVD ALLHAT
RR (95%CI) P value
L/A 1.03 (0.94-1.13) 0.54
RR (95%CI) P value
L/A 1.08 (0.99-1.15) 0.06
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
0.40
0.45
0.50
Cu
mu
lati
ve
CC
VD
Ra
te
0 1 2 3 4 5 6 7
Years to CCVD
AmlodipineLisinopril
CHD at BL
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
0.40
0.45
0.50
0 1 2 3 4 5 6 7
Years to CCVD
AmlodipineLisinopril
No CHD at BL
SummaryALLHAT
Lisinopril vs. Amlodipine
CHD at baseline No CHD at baseline
CHD, mortality,ESRD
similar similar
Stroke +31% +20%
HFAnginaPAD
-9%-1%-7%
-15%+17% (p=0.07 for interaction)
+39% (p=0.02 for interaction)
Treated SBP level similar + 1-2 mmHg
Combined CVD +3% +8%
ConclusionALLHAT
In hypertensive patients with CHD, lisinopril and amlodipine – based treatment provides equivalent BP control and equivalent rates for most outcomes.
Patients with and without CHD have similar higher stroke rates and lower HF rates on lisinopril versus amlodipine.
This post-hoc analysis provides no evidence for specific benefits by ACE-inhibitor based treatment in patients with CHD.
Events for CHD by RaceRelative Risk and 95% Confidence Intervals
Revascularization
Combined CVD
Combined CHD
Non-Blacks
Favors Lisinopril Favors Amlodipine
0.50 1 2
PAD 0.98 (0.72-1.33)
1.00 (0.84-1.19)
Angina 0.99 (0.86-1.14)
HF 0.90 (0.73-1.11)
GI Bleed 1.00 (0.77-1.30)
Cancer 1.03 (0.82-1.31)
ESRD 0.65 (0.33-1.29)
1.03 (0.93-1.15)
Stroke 1.20 (0.89-1.62)
1.07 (0.95-1.22)
Death 1.15 (0.97-1.36)
CHD 1.08 (0.90-1.30)
Blacks
Favors Lisinopril Favors Amlodipine
0.50 1 2
0.76 (0.43-1.35)
1.17 (0.79-1.73)
0.98 (0.73-1.33)
0.95 (0.66-1.35)
1.20 (0.78-1.86)
0.92 (0.61-1.40)
1.72 (0.68-4.38)
1.02 (0.84-1.24)
1.63 (1.01-2.64)
1.06 (0.82-1.37)
1.14 (0.87-1.49)
0.95 (0.68-1.35)
ALLHAT
Non-Blacks
Favors Lisinopril Favors Amlodipine
0.50 1 2
PAD 1.35 (1.04-1.77)
Revascularization 0.95 (0.82-1.12)
Angina 1.12 (0.96-1.31)
HF 0.83 (0.69-0.99)
GI Bleed 1.27 (1.03-1.55)
Cancer 0.95 (0.81-1.11)
ESRD 0.97 (0.63-1.49)
Combined CVD 1.02 (0.93-1.12)
Stroke 1.00 (0.79-1.25)
Combined CHD 0.97 (0.86-1.09)
Death 0.96 (0.85-1.09)
CHD 0.91 (0.78-1.06)
Blacks
Favors Lisinopril Favors Amlodipine
0.50 1 2
1.44 (1.03-2.02)
1.08 (0.81-1.45)
1.24 (1.01-1.52)
0.87 (0.71-1.08)
1.30 (1.03-1.64)
1.10 (0.90-1.34)
1.03 (0.71-1.48)
1.16 (1.03-1.30)
1.48 (1.17-1.88)
1.14 (0.97-1.33)
1.08 (0.94-1.25)
1.17 (0.95-1.43)
Events for No CHD by RaceRelative Risk and 95% Confidence IntervalsALLHAT
ALLHAT Events for Non-Blacks by CHD StatusRelative Risk and 95% Confidence Intervals
No CHD at Baseline
Favors Lisinopril Favors Amlodipine
0.50 1 2
1.35 (1.04-1.77)
0.95 (0.82-1.12)
1.12 (0.96-1.31)
0.83 (0.69-0.99)
1.27 (1.03-1.55)
0.95 (0.81-1.11)
0.97 (0.63-1.49)
1.02 (0.93-1.12)
1.00 (0.79-1.25)
0.97 (0.86-1.09)
0.96 (0.85-1.09)
0.91 (0.78-1.06)
CHD at Baseline
Favors Lisinopril Favors Amlodipine
0.50 1 2
PAD 0.98 (0.72-1.33)
1.00 (0.84-1.19)
Angina 0.99 (0.86-1.14)
HF 0.90 (0.73-1.11)
GI Bleed 1.00 (0.77-1.30)
Cancer 1.03 (0.82-1.31)
ESRD 0.65 (0.33-1.29)
1.03 (0.93-1.15)
Stroke 1.20 (0.89-1.62)
1.07 (0.95-1.22)
Death 1.15 (0.97-1.36)
CHD 1.08 (0.90-1.30)
Revascularization
Combined CVD
Combined CHD
ALLHATEvents for Blacks by CHD Status
Relative Risk and 95% Confidence Intervals
PAD
Revascularization
Angina
HF
GI Bleed
Cancer
ESRD
Combined CVD
Stroke
Combined CHD
Death
CHD
CHD at Baseline
Favors Lisinopril Favors Amlodipine
0.50 1 2
0.76 (0.43-1.35)
1.17 (0.79-1.73)
0.98 (0.73-1.33)
0.95 (0.66-1.35)
1.20 (0.78-1.86)
0.92 (0.61-1.40)
1.72 (0.68-4.38)
1.02 (0.84-1.24)
1.63 (1.01-2.64)
1.06 (0.82-1.37)
1.14 (0.87-1.49)
0.95 (0.68-1.35)
No CHD at Baseline
Favors Lisinopril Favors Amlodipine
0.50 1 2
1.44 (1.03-2.02)
1.08 (0.81-1.45)
1.24 (1.01-1.52)
0.87 (0.71-1.08)
1.30 (1.03-1.64)
1.10 (0.90-1.34)
1.03 (0.71-1.48)
1.16 (1.03-1.30)
1.48 (1.17-1.88)
1.14 (0.97-1.33)
1.08 (0.94-1.25)
1.17 (0.95-1.43)
Outcomes L vs. A:RR and 95% Confidence Intervals
CHD at Baseline
Favors Lisinopril Favors Amlodipine
0.50 1 2
PAD 0.93 (0.71-1.21)
Revascularization 1.03 (0.88-1.20)
Angina 0.99 (0.87-1.12)
HF 0.91 (0.76-1.09)
GI Bleed 1.05 (0.84-1.32)
Cancer 1.01 (0.82-1.24)
ESRD 0.92 (0.54-1.56)
Combined CVD 1.03 (0.94-1.13)
Stroke 1.31 (1.01-1.69)
Combined CHD 1.07 (0.96-1.20)
Death 1.15 (0.99-1.32)
CHD 1.05 (0.89-1.24)
No CHD at Baseline
Favors Lisinopril Favors Amlodipine
0.50 1 2
1.39 (1.12-1.71)
0.98 (0.86-1.13)
1.17 (1.03-1.32)
0.85 (0.74-0.97)
1.28 (1.10-1.50)
1.01 (0.89-1.14)
1.00 (0.76-1.32)
1.07 (0.99-1.15)
1.20 (1.02-1.41)
1.02 (0.93-1.12)
1.01 (0.92-1.11)
0.99 (0.88-1.13)
ALLHAT
Outcomes A vs. C:RR and 95% Confidence Intervals
No CHD at Baseline
Favors Amlodipine Favors Chlorthalidone0.50 1 2
0.79 (0.66-0.96)
1.08 (0.96-1.23)
0.99 (0.88-1.11)
1.48 (1.30-1.68)
0.88 (0.76-1.02)
1.06 (0.95-1.18)
1.23 (0.95-1.60)
1.05 (0.98-1.12)
0.96 (0.82-1.11)
1.02 (0.93-1.11)
0.99 (0.91-1.08)
1.01 (0.90-1.13)
CHD at Baseline
Favors Amlodipine Favors Chlorthalidone0.50 1 2
PAD 1.04 (0.82-1.31)
Revascularization 1.16 (1.00-1.33)
Angina 1.10 (0.98-1.24)
HF 1.29 (1.09-1.52)
GI Bleed 1.00 (0.82-1.23)
Cancer 0.92 (0.77-1.10)
ESRD 0.88 (0.56-1.38)
Combined CVD 1.07 (0.98-1.16)
Stroke 0.90 (0.71-1.13)
Combined CHD 1.02 (0.92-1.13)
Death 0.89 (0.79-1.01)
CHD 0.95 (0.82-1.10)
ALLHAT
Outcomes A vs. C in Blacks:RR and 95% Confidence Intervals
CHD at Baseline in Blacks
Favors Amlodipine Favors Chlorthalidone
0.50 1 2
PAD 1.18 (0.73-1.91)
Revascularization 1.37 (0.94-1.99)
Angina 1.08 (0.83-1.41)
HF 1.47 (1.06-2.04)
GI Bleed 0.94 (0.63-1.39)
Cancer 1.07 (0.75-1.55)
ESRD0.70 (0.29-1.68)
Combined CVD 1.16 (0.97-1.38)
Stroke 0.89 (0.56-1.42)
Combined CHD 1.19 (0.94-1.50)
Death 0.96 (0.76-1.23)
CHD 1.19 (0.87-1.61)
No CHD at Baseline in Blacks
Favors Amlodipine Favors Chlorthalidone
0.50 1 2
0.77 (0.56-1.05)
0.97 (0.75-1.27)
1.10 (0.91-1.35)
1.53 (1.26-1.88)
1.01 (0.81-1.26)
0.95 (0.79-1.14)
1.27 (0.90-1.80)
1.05 (0.94-1.16)
0.96 (0.76-1.21)
1.00 (0.87-1.16)
0.99 (0.87-1.13)
0.95 (0.79-1.15)
ALLHAT
Outcomes A vs. C in Non-Blacks:RR and 95% Confidence Intervals
CHD at Baseline in Non-Blacks
Favors Amlodipine Favors Chlorthalidone
0.50 1 2
PAD 1.00 (0.76-1.31)
Revascularization 1.12 (0.96-1.30)
Angina 1.11 (0.97-1.26)
HF 1.24 (1.03-1.49)
GI Bleed 1.03 (0.81-1.30)
Cancer 0.87 (0.71-1.08)
ESRD 1.96 (0.56-1.62)
Combined CVD 1.04 (0.95-1.14)
Stroke 0.90(0.69-1.18)
Combined CHD 0.98 (0.87-1.10)
Death 0.87 (0.75-1.01)
CHD 0.89 (0.76-1.05)
No CHD at Baseline in Non-Blacks
Favors Amlodipine Favors Chlorthalidone
0.50 1 2
0.81 (0.64-1.04)
1.12 (0.97-1.29)
0.94 (0.82-1.08)
1.44 (1.23-1.70)
0.80 (0.67-0.97)
1.13 (0.98-1.30)
1.18 (0.79-1.74)
1.05 (0.97-1.14)
0.95 (0.78-1.16)
1.02 (0.92-1.17)
0.99 (0.89-1.11)
1.04 (0.91-1.10)
ALLHAT
Outcomes L vs. C:RR and 95% Confidence Intervals
No CHD at Baseline
Favors Lisinopril Favors Chlorthalidone0.50 1 2
1.10 (0.92-1.31)
1.06 (0.94-1.21)
1.16 (1.04-1.29)
1.25 (1.09-1.43)
1.13 (1.00-1.29)
1.06 (0.95-1.19)
1.23 (0.95-1.60)
1.12 (1.05-1.20)
1.15 (1.00-1.32)
1.04 (0.96-1.13)
1.01 (0.93-1.09)
1.00 (0.90-1.12)
CHD at Baseline
Favors Lisinopril Favors Chlorthalidone0.50 1 2
PAD 0.96 (0.76-1.22)
Revascularization 1.18 (1.03-1.36)
Angina 1.09 (0.97-1.22)
HF 1.18 (1.00-1.39)
GI Bleed 1.06 (0.87-1.29)
Cancer 0.93 (0.77-1.11)
ESRD 0.80 (0.51-1.28)
Combined CVD 1.10 (1.01-1.19)
Stroke 1.17 (0.95-1.45)
Combined CHD 1.09 (0.99-1.21)
Death 1.02 (0.91-1.15)
CHD 1.00 (0.87-1.15)
ALLHAT
Outcomes L vs. C in Blacks:RR and 95% Confidence Intervals
CHD at Baseline in Blacks
Favors Lisinopril Favors Chlorthalidone
0.50 1 2
PAD 0.90 (0.54-1.53)
Revascularization 1.59(1.11-2.28)
Angina 1.06 (0.81-1.38)
HF 1.39 (0.99-1.94)
GI Bleed 1.13 (0.78-1.64
Cancer 1.00 (0.69-1.45)
ESRD 1.21 (0.58-2.52)
Combined CVD 1.18 (0.99-1.40)
Stroke 1.45 (0.98-2.16)
Combined CHD 1.26 (1.01-1.59)
Death 1.10 (0.88-1.39)
CHD 1.14 (0.83-1.55)
No CHD at Baseline in Blacks
Favors Lisinopril Favors Chlorthalidone
0.50 1 2
1.11 (0.84-1.47)
1.05 (0.81-1.36)
1.37 (1.14-1.65)
1.34 (1.09-1.65)
1.32 (1.07-1.62)
1.04 (0.88-1.24)
1.30 (0.92-1.83)
1.22 (1.10-1.35)
1.43 (1.16-1.76)
1.14 (0.99-1.32)
1.07 (0.95-1.22)
1.11 (0.93-1.33)
ALLHAT
Outcomes L vs. C in Non-Blacks:RR and 95% Confidence Intervals
No CHD at Baseline in Non-Blacks
Favors Lisinopril Favors Chlorthalidone
0.50 1 2
1.10 (0.88-1.37)
1.07 (0.93-1.24)
1.06 (0.92-1.21)
1.19 (1.00-1.42)
1.02 (0.85-1.21)
1.08 (0.93-1.24)
1.15 (0.77-1.71)
1.07 (0.99-1.16)
0.95 (0.77-1.16)
0.99 (0.89-1.10)
0.96 (0.86-1.07)
0.94 (0.82-1.09)
CHD at Baseline in Non-Blacks
Favors Lisinopril Favors Chlorthalidone
0.50 1 2
PAD 0.98 (0.75-1.28)
Revascularization 1.12 (0.96-1.30)
Angina 1.10 (0.96-1.24)
HF 1.12 (0.92-1.35)
GI Bleed 1.03 (0.82-1.30)
Cancer 0.91 (0.74-1.11)
ESRD 0.63 (0.34-1.16)
Combined CVD 1.08 (0.98-1.18)
Stroke 1.08 (0.83-1.39)
Combined CHD 1.05 (0.94-1.17)
Death 1.00 (0.86-1.15)
CHD 0.97(0.83-1.13)
ALLHAT