Outcomes in High Risk Hypertensives Randomized to CCB vs. ACE Inhibitor in ALLHAT
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Outcomes in High Risk Hypertensives Randomized to CCB vs. ACE Inhibitor 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) U.S. Department of Health and Human Services National Institutes of Health National Heart, Lung, and Blood Institute ALLHAT ALLHAT www.allhat.or g
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ALLHAT. U.S. Department of Health and Human Services. National Institutes of Health. National Heart, Lung, and Blood Institute. Outcomes in High Risk Hypertensives Randomized to CCB vs. ACE Inhibitor in ALLHAT. - PowerPoint PPT Presentation
Transcript of Outcomes in High Risk Hypertensives Randomized to CCB vs. ACE Inhibitor in ALLHAT
Outcomes in High Risk Hypertensives Randomized to CCB
vs. ACE Inhibitor 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)
U.S. Department of Health and Human
Services
National Institutes of Health
National Heart, Lung, and Blood Institute
ALLHATALLHAT
www.allhat.org
Primary ObjectivePrimary Objective
Determine whether treatment with the newer agents (CCB, ACEI, alpha-blocker) results in less fatal CHD and nonfatal MI compared with a diuretic
Determine whether treatment with the newer agents (CCB, ACEI, alpha-blocker) results in less fatal CHD and nonfatal MI compared with a diuretic
POST-HOC ANALYSIS - Comparison of cardiovascular and other outcomes among 18,102 patients randomized to ACEI or dihydropyridine CCB- For sub-groups, emphasis on outcomes in Blacks vs non-Blacks considering the previously reported interaction for several major outcomes with lisinopril.
POST-HOC ANALYSIS - Comparison of cardiovascular and other outcomes among 18,102 patients randomized to ACEI or dihydropyridine CCB- For sub-groups, emphasis on outcomes in Blacks vs non-Blacks considering the previously reported interaction for several major outcomes with lisinopril.
ALLHATALLHAT
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
Baseline Characteristics
Amlodipine(n=9048)
Lisinopril(n=9054)
P valueLisinopril vs. Amlodipine
Age in yrs, mean (SD) 66.9 (7.7) 66.9 (7.7) 0.83
On antihypertensive meds (%) 8171 (90) 8164 (90) 0.83
Type 2 diabetes (%) 3323 (37) 3212 (35) 0.08
History of CHD (%) 2202 (24) 2270 (25) 0.25
Cigarette smoker (%) 1980 (22) 1981 (22) 0.90
Female (%) 4280 (47) 4187 (46) 0.15
Blacks (%) 3213 (36) 3210 (35) 0.94
On aspirin (%) 3268 (36) 3258 (36) 0.85
ALLHATALLHAT
Baseline and Follow-up Blood PressuresBaseline and Follow-up Blood PressuresALLHAT
74
76
78
80
82
84
86
3m
53255637
Y3
60766381
Y2 Y4 Y16mBLNumber at Risk:
670075219054688376099048Amlodipine
mm
Hg
BP
74
76
78
80
82
84
86
mm
Hg
BP
74
76
78
80
82
84
86
74
76
78
80
82
84
86
3m Y3Y2 Y4 Y16mBL 3m Y3Y2 Y4 Y16mBL
Lisinopril
mm
Hg
BP
134
136
138
140
142
144
146
148
mm
Hg
BP
134
136
138
140
142
144
146
148
134
136
138
140
142
144
146
148
Amlodipine
Lisinopril
mm
Hg
BP
Baseline and Follow-up BPs by RaceBaseline and Follow-up BPs by RaceALLHAT
132
134
136
138
140
142
144
146
148
Amlodipine - BlacksAmlodipine - Non-BlacksLisinopril - BlacksLisinopril - Non-Blacks
mm
Hg
SB
P
74
76
78
80
82
84
86
3m
2.01.8
1.71.8
Y3
1.91.7
1.61.7
Y2 Y4 Y16mBL
Mean # of Meds:
1.81.6
1.61.4
1.51.5
1.41.4
Amlodipine BlacksNon-Blacks-
Lisinopril BlacksNon-Blacks
-
mm
Hg
DB
P
Δ=1.6
Δ=3.4
Δ=1.8
Δ=0.5
Δ=1.1
Δ=0.8
Years to CHD Event0 1 2 3 4 5 6 7
Cumulative CHD Event Rate
0
.04
.08
.12
.16
.2
Number at Risk:
Amlodipine 9,048 8,576 8,218 7,843 6,824 3,870 1,878 215 Lisinopril 9,054 8,535 8,123 7,711 6,662 3,832 1,770 195
Cumulative Event Rates for the Primary Outcome (Fatal CHD or Nonfatal MI) by
Treatment Group
RR (95% CI) p value
L/A 1.01 (0.91-1.11) 0.85
ALLHAT
AmlodipineLisinopril
Blacks 1.09 (0.92-1.30) 0.33
Non-Blacks 0.97 (0.86-1.10) 0.66
Secondary Endpoints:No Differences Between Treatment Groups ForALLHAT
Lisinopril vs. Amlodipine
RR (95% CI) P value
Combined CHD 1.04 (0.97-1.12) 0.24
All-Cause Mortality 1.05 (0.97-1.13) 0.21
ESRD 0.99 (0.77-1.26) 0.93
Blacks (L vs. A) Non-Blacks (L vs. A)
RR (95% CI) P value RR (95% CI) P value
Combined CHD 1.12 (0.98-1.28) 0.11 1.02 (0.93-1.11) 0.73
All-Cause Mortality 1.01 (0.96-1.23) 0.19 1.03 (0.93-1.13) 0.59
ESRD 1.12 (0.80-1.57) 0.51 0.86 (0.60-1.24) 0.43
Cumulative Stroke Rate
0
0
.02
.04
.06
.08
.1
Years to Stroke1 2 3 4 5 6 7
Number at risk:
Amlodipine 9,048 8,617 8,271 7,949 6,937 3,845 1,813 506 Lisinopril 9,054 8,543 8,172 7,784 6,765 3,891 1,828 949
Cumulative Event Rates for Stroke by Treatment Group
RR (95% CI) p value
L/A 1.23 (1.08-1.41) 0.003
ALLHAT
AmlodipineLisinopril
Cumulative Event Rates for Stroke by Race and Treatment Group
Cu
mu
lati
ve S
tro
ke R
ate
0.00
0.05
0.10
0 1 2 3 4 5 6 7
Years to Stroke
AmlodipineLisinopril
Blacks
0.00
0.05
0.10
0 1 2 3 4 5 6 7
Years to Stroke
AmlodipineLisinopril
Non-Blacks
ALLHAT
RR (95%CI) P value
L/A 1.51 (1.22-1.86) <0.001
RR (95%CI) P value
L/A 1.07 (0.89-1.28) 0.47
Stroke Interaction by Gender and RaceStroke Interaction by Gender and Race
Blacks Non-Blacks
Males Females Males Females
6 Yr Event Rate per 100 Pts
9.2 vs 6.7 7.0 vs 4.9 5.2 vs 5.9 5.3 vs 3.7
Δ + 37 % + 45 % - 11 % + 46 %
p=0.02 for interaction of gender within non-blacks
ALLHAT
Lisinopril versus Amlodipine
+ favors amlodipine- favors lisinopril
Cumulative Combined CVD Event Rate
0
0
.1
.2
.3
.4
.5
Number at risk:
Years to Combined CVD Event1 2 3 4 5 6 7
Amlodipine 9,048 8,118 7,451 6,837 5,724 3,049 1,411 153 Lisinopril 9,054 7,962 7,259 6,631 5,560 3,011 1,375 139
Cumulative Event Rates for Combined CVD by Treatment Group ALLHAT
AmlodipineLisinopril
Blacks 1.13 (1.02-1.24) 0.02
Non-Blacks 1.03 (0.96-1.10) 0.47
RR (95% CI) p value
L/A 1.06 (1.00-1.12) 0.047
Other Components of Combined CVDOther Components of Combined CVD
Amlodipine Lisinopril Lisinopril vs Amlodipine
No. of Total
Events
6-yr rateper 100Persons
(SE)
No. of Total
Events
6-yr rate per 100
Persons (SE)
RR(95% CI)
PValue
Heart failure 706 10.2 (0.4) 612 8.7 (0.4) 0.87 (0.78-0.96)*
0.007
Hospitalized/fatal heart failure
578 8.4 (0.4) 471 6.9 (0.4) 0.81(0.72-0.9)*
<0.001
Angina (hospitalized or treated)
950 12.6 (0.4) 1019 13.6 (0.4) 1.09(1.00-1.19)
0.055
Angina (hospitalized) 630 8.4 (0.4) 693 9.6 (0.4) 1.12(1.00-1.24)
0.045
Coronary revascularizations
725 10.0 (0.4) 718 10.2 (0.4) 1.00(0.91-1.11)
0.943
Peripheral arterial disease (hospitalizedor fatal)
265 3.7 (0.2) 311 4.7 (0.4) 1.19(1.01-1.40)
0.036
* 2X2 table RR rather than Cox PH
ALLHAT
Cumulative HF Rate
0
0
.03
.06
.09
.12
.15
Years to HF1 2 3 4 5 6 7
Cumulative Event Rates for Heart Failure by Treatment Group ALLHAT
AmlodipineLisinopril
Number at risk:
Amlodipine 9,048 8,535 8,185 7,801 6,785 3,775 1,780 210 Lisinopril 9,054 8,496 8,096 7,689 6,698 3,789 1,837 313
RR (95% CI) p value
L/A 0.87 (0.78-0.96) 0.007
Blacks 0.89 (0.75-1.06) 0.18
Non-Blacks 0.85 (0.75-0.97) 0.02
Safety ParametersALLHAT
Lisinopril vs. Amlodipine
RR (95% CI) P value
Cancer 1.01 (0.91-1.12) 0.91GI Bleed 1.20 (1.06-1.37) 0.004
Lisinopril (n) Amlodipine (n) P value
Angioedema 38 3 <0.001
Blacks (L vs. A) Non-Blacks (L vs. A)
RR (95% CI) P value RR (95% CI) P value
Cancer 1.06 (0.89-1.26) 0.54 0.98 (0.86-1.12) 0.75
GI Bleed 1.28 (1.04-1.56) 0.02 1.16 (0.99-1.36) 0.07
Blacks (n) Non-Blacks (n)
Lisinopril Amlodipine P Lisinopril Amlodipine P
Angioedema 23 2 <0.001 15 1 <0.001
SummaryLisinopril vs. Amlodipine
ALLHAT
Non-Blacks Blacks
SBP Control <+0.5 mmHg + 2-3 mmHg# antihypertensive drugs similar + 0.3
CHD, Combined CHD, Mortality, ESRD, cancer
similar similar
Stroke similarbut men -11%, women +46%
+ 45%
Combined CVD
HF
similar
- 15%
+ 13%
- 11%
GI Bleed + 16% + 28%
Angioedema > >>
+favors amlodipine- favors lisinopril
ConclusionsNon-Black Older HypertensivesAt apparently equivalent BP control, most outcomes are similar on lisinopril vs. amlodipine-initiated treatment except for
• less HF on lisinopril• more strokes (in women), GI bleed, and angioedema on lisinopril
ALLHAT
Black Older HypertensivesSeveral outcomes are similar on lisinopril vs. amlodipine-initiated treatment, but
• Less HF on lisinopril• Less BP control and more cardiovascular events, including stroke, on lisinopril• more GI bleeds and angioedema on lisinopril
Clinical ImplicationsALLHAT was not designed to identify the best step-one drug alternative if a thiazide-type diuretic cannot be used. However, considering the totality of the outcome measures, amlodipine would appear to have an advantage over lisinopril, particularly in Blacks and Women, but this depends on how clinicians weigh outcomes that favor the respective arms.
