Post on 14-Jan-2016
7/27/2006
Outcomes in Hypertensive Black
and Nonblack Patients Treated with
Chlorthalidone, Amlodipine, and
Lisinopril*
*Wright JT, Dunn JK, Cutler JA et al. JAMA 2005:293:1595-1608.
ALLHAT
7/27/2006
Randomized Design Randomized Design of ALLHAT BP Trialof ALLHAT BP Trial
42,41842,418
High-risk High-risk hypertensive hypertensive patientspatients
Consent / Consent / RandomizeRandomize
AmlodipineAmlodipine
ChlorthalidoneChlorthalidone
DoxazosinDoxazosin
LisinoprilLisinopril
Follow until death or end of study (4-8 years, mean 4.9 years)Follow until death or end of study (4-8 years, mean 4.9 years)
ALLHAT
7/27/2006
• ALLHAT reported no differences in the primary ALLHAT reported no differences in the primary CHD outcome, but overall superiority of thiazide-CHD outcome, but overall superiority of thiazide-type diuretic for first-step therapy of hypertension type diuretic for first-step therapy of hypertension based on based on differences differences in secondaryin secondary outcomes outcomes
• The population of blacks with hypertension has The population of blacks with hypertension has the highest morbidity and mortality from the highest morbidity and mortality from hypertension of any population group in the U.S. hypertension of any population group in the U.S.
• Race was a prespecified subgroup for ALLHATRace was a prespecified subgroup for ALLHAT
Race Subgroup AnalysisALLHAT
7/27/2006
Baseline Characteristics by Race(Chlorthalidone, Amlodipine, Lisinopril)
Black Non-Black
N 11,792 21,565
Age – mean (sd) 66.3 (7.8) 67.2 (7.6)
Women (%) 54.5 42.7
SBP – mean (sd) 146.2 (15.8) 146.3 (15.6)
DBP – mean (sd) 84.8 (10.2) 83.6 (10.0)
Current smokers (%) 25.1 20.1
ASCVD (%) 44.8 55.2
Diabetes Classification (%)
Diabetes 46.3 39.0
Impaired fasting glucose 3.8 4.8
Normoglycemic 49.9 56.2
LVH by ECG (%) 23.9 12.3
HDL-C – mean (sd) mg/dl 51.7 (15.6) 44.3 (13.5)
ALLHAT
7/27/2006
Chlorthalidone Amlodipine Lisinopril
SBP – mean (sd)Black 135.0 (15.8) 136.1 (15.3) 139.1 (19.7)
Non-black
133.3 (14.8) 133.8 (14.6) 134.2 (16.7)
DBP – mean (sd)Black 77.4 (10.0) 76.3 (10.1) 78.0 (11.4)
Non-black
74.4 (9.5) 73.6 (9.6) 74.1 (10.1)
∆ SBP/DBP compared with chlorthalidone
Black --- +1.1 / -0.7 +5.2* / +1.4*
Non-black
--- +0.2 / -1.1* +0.5 / -0.5
Blood Pressure at 5 Yearsby Race
* P < 0.005 compared to Chlorthalidone
ALLHAT
7/27/2006
Black-Chlor Black–Amlod Black–Lisin
Nonblack–Chlor Nonblack–Amlod Nonblack–Lisin
BP Results by Treatment Group by RaceALLHAT
7/27/2006
% on 3+ Antihypertensive % on 3+ Antihypertensive Drugs by Randomized Group Drugs by Randomized Group
and Race at 5 Yearsand Race at 5 Years
28.324.924.423.8
31.1
40.7
0
20
40
60
Black Non-Black
Per
cen
t
Chlorthalidone Amlodipine Lisinopril
ALLHAT
7/27/2006
BP Control (<140/90 mm Hg) BP Control (<140/90 mm Hg) and Mean BP by Randomized and Mean BP by Randomized
Group and Race at 5 YearsGroup and Race at 5 Years
626870
64 65
54
0
20
40
60
80
Black Non-Black
Per
cen
t
Chlorthalidone Amlodipine Lisinopril
135/78135/78 136/76136/76 139/79139/79 133/74133/74 134/74134/74 134/74134/74
ALLHAT
7/27/2006
Serum PotassiumSerum Potassium(mean mmol/l)(mean mmol/l)
by Treatment Group and Raceby Treatment Group and Race
ChlorChlor AmlodAmlod LisinLisin
BlackBlack BaselineBaseline 4.34.3 4.34.3 4.34.3
2 Years2 Years 4.04.0 4.34.3 4.44.4
4 Years4 Years 4.14.1 4.44.4 4.44.4
Non-BlackNon-Black BaselineBaseline 4.44.4 4.44.4 4.44.4
2 Years2 Years 4.14.1 4.44.4 4.54.5
4 Years4 Years 4.24.2 4.44.4 4.64.6
ALLHAT
7/27/2006
Serum CholesterolSerum Cholesterol(mean mg/dl)(mean mg/dl)
by Treatment Group and Raceby Treatment Group and Race
ChlorChlor AmlodAmlod LisinLisin
BlackBlack BaselineBaseline 218218 218218 217217
2 Years2 Years 209209 204204 204204
4 Years4 Years 202202 199199 198198
Non-BlackNon-Black BaselineBaseline 215215 216216 215215
2 Years2 Years 204204 202202 201201
4 Years4 Years 195195 194194 194194
ALLHAT
7/27/2006
Fasting Glucose(mean mg/dl)
by Treatment Group and RaceChlor Amlod Lisin
Black Baseline 127127 126126 127127
2 Years 130130 128128 124124
4 Years 130130 126126 125125
Non-Black Baseline 122122 122122 121121
2 Years 126126 120120 119119
4 Years 125125 123123 120120
ALLHAT
7/27/2006
Fasting Glucose 126 mg/dlby Treatment Group and Race
Chlor Amlod Lisin
Black Baseline 31%31% 32%32% 31%31%
2 Years 35%35% 34%34% 29%29%
4 Years 34%34% 33%33% 28%28%
Non-Black Baseline 28%28% 28%28% 28%28%
2 Years 32%32% 28%28% 28%28%
4 Years 32%32% 30%30% 29%29%
ALLHAT
7/27/2006
Black vs. Non-BlackAmlodipine/Chlorthalidone
Relative Risk and 95% Confidence Intervals
Nonfatal MI + CHD Death
All-Cause Mortality
Combined CHD
Combined CVD
Stroke
End Stage Renal Disease
Heart Failure
Black
Favors Amlodipin
e
0.50 1 2
1.46 (1.24 - 1.73)
1.15 (0.84 - 1.58)
0.93 (0.76 - 1.14)
1.06 (0.96 - 1.16)
1.03 (0.91 - 1.17)
0.97 (0.87 - 1.09)
1.01 (0.86 - 1.18)
Favors Chlorthalidon
e
Non-Black
0.50 1 2
1.32 (1.17 - 1.49)
1.08 (0.79 - 1.48)
0.93 (0.79 - 1.10)
1.04 (0.97 - 1.10)
0.99 (0.92 - 1.07)
0.94 (0.87 - 1.03)
0.97 (0.87 - 1.08)
Favors Amlodipin
e
Favors Chlorthalidon
e
ALLHAT
7/27/2006
ALLHAT Black vs. Non-BlackLisinopril/Chlorthalidone
Relative Risk and 95% Confidence Intervals
Nonfatal MI + CHD Death
All-Cause Mortality
Combined CHD
Combined CVD
Stroke
End Stage Renal Disease
Heart Failure
Black
Favors Lisinopril
Favors Chlorthalidon
e
0.50 1 2
1.30 (1.10 - 1.54)
1.29 (0.94 - 1.75)
1.40 (1.17 - 1.68)
1.19 (1.09 - 1.30)
1.15 (1.02 - 1.30)
1.06 (0.95 - 1.18)
1.10 (0.94 - 1.28)
Non-Black
Favors Lisinopri
l
Favors Chlorthalidone
0.50 1 2
1.13 (1.00 - 1.28)
0.93 (0.67 - 1.30)
1.00 (0.85 - 1.17)
1.06 (1.00 - 1.13)
1.01 (0.93 - 1.09)
0.97 (0.89 - 1.06)
0.94 (0.85 - 1.05)
0
4
8
12C
um
ula
tive
HF
Rat
e, %
0 1 2 3 4 5 6
Years to HF
Chlorthalidone Amlodipine Lisinopril
Heart Failure Rate for Blacksby Treatment Group
No. at RiskNo. at Risk
AmlodipineAmlodipine 32133213 28792879 24232423 720720
LisinoprilLisinopril 32103210 28372837 23612361 711711
ChlorthalidoneChlorthalidone 53695369 48384838 40414041 11751175
ALLHAT
0
4
8
12C
um
ula
tive
HF
Rat
e, %
0 1 2 3 4 5 6
Years to HF
Chlorthalidone
Amlodipine
Lisinopril
Heart Failure Rate for Non-BlacksBy Treatment Group
No. at RiskNo. at Risk
AmlodipineAmlodipine 58355835 53075307 43744374 11301130
LisinoprilLisinopril 58445844 52625262 43384338 11321132
ChlorthalidoneChlorthalidone 98869886 90679067 74797479 19681968
ALLHAT
7/27/2006
ANGIOEDEMA
Total BlacksNon-
blacks
Chlorthalidone 8 / 15,255
0.1%
2 / 5,369
<0.1%
6 / 9,886
0.1%
Lisinopril 41 / 9,054
0.5%
23 / 3,210
0.7%
18 / 5,844
0.3%p<.001 p<.001 p=.002
There were 3 cases (<0.1%) of angioedema in the amlodipine group (comparison to chlorthalidone not significant).
ALLHAT
7/27/2006
Antihypertensive Trial:Implications
• Diuretics should be the drug of choice for initial therapy of hypertension. The evidence for this recommendation is even stronger for Black hypertensive patients..
• For the patient who cannot take a diuretic (which should be an unusual circumstance), CCB’s and ACEI’s may be considered. However, in Black hypertensive patients, ACEI’s should be considered second-line therapy.
• Most hypertensive patients require more than one drug. Diuretics should generally be part of the antihypertensive regimen. Lifestyle advice should also be provided.
ALLHAT
7/27/2006
Extra Slides
7/27/2006
Nonfatal MI + CHD Death 1.01 (0.86 - 1.18)
All-Cause Mortality 0.97 (0.87 - 1.09)
Combined CHD 1.03 (0.91 - 1.17)
Combined CVD 1.06 (0.96 - 1.16)
Stroke 0.93 (0.76 - 1.14)
Heart Failure 1.46 (1.24 - 1.73)
End Stage Renal Disease 1.15 (0.84 - 1.58)
BlacksAmlodipine/Chlorthalidone
Relative Risk and 95% Confidence Intervals
Favors Amlodipine Favors Chlorthalidone
0.50 1 2
ALLHAT
7/27/2006
Nonfatal MI + CHD Death 1.10 (0.94 - 1.28)
All-Cause Mortality 1.06 (0.95 - 1.18)
Combined CHD 1.15 (1.02 - 1.30)
Combined CVD 1.19 (1.09 - 1.30)
Stroke 1.40 (1.17 - 1.68)
Heart Failure 1.30 (1.10 - 1.54)
End Stage Renal Disease 1.29 (0.94 - 1.75)
BlacksLisinopril/Chlorthalidone
Relative Risk and 95% Confidence Interval
Favors Lisinopril Favors Chlorthalidone
0.50 1 2
ALLHAT
7/27/2006
Nonfatal MI + CHD Death 0.97 (0.87 - 1.08)
All-Cause Mortality 0.94 (0.87 - 1.03)
Combined CHD 0.99 (0.92 - 1.07)
Combined CVD 1.04 (0.97 - 1.10)
Stroke 0.93 (0.79 - 1.10)
Heart Failure 1.32 (1.17 - 1.49)
End Stage Renal Disease 1.08 (0.79 - 1.48)
Non-BlacksAmlodipine/Chlorthalidone
Relative Risk and 95% Confidence Intervals
Favors Amlodipine Favors Chlorthalidone
0.50 1 2
ALLHAT
7/27/2006
Nonfatal MI + CHD Death 0.94 (0.85 - 1.05)
All-Cause Mortality 0.97 (0.89 - 1.06)
Combined CHD 1.01 (0.93 - 1.09)
Combined CVD 1.06 (1.00 - 1.13)
Stroke 1.00 (0.85 - 1.17)
Heart Failure 1.13 (1.00 - 1.28)
End Stage Renal Disease 0.93 (0.67 - 1.30)
Non-BlacksLisinopril/Chlorthalidone
Relative Risk and 95% Confidence Intervals
Favors Lisinopril Favors Chlorthalidone
0.50 1 2
ALLHAT