7/27/2006 outcomes in hypertensive black and nonblack patients treated with chlorthalidone,...

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


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


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


e

ALLHAT

7/27/2006

ALLHAT Black vs. Non-BlackLisinopril/Chlorthalidone


Nonfatal MI + CHD Death

All-Cause Mortality

Combined CHD

Combined CVD

Stroke

End Stage Renal Disease

Heart Failure

Black

Favors Lisinopril


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


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


Favors Amlodipine Favors Chlorthalidone

0.50 1 2

ALLHAT

7/27/2006



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)


BlacksLisinopril/Chlorthalidone

Relative Risk and 95% Confidence Interval

Favors Lisinopril Favors Chlorthalidone

0.50 1 2

ALLHAT

7/27/2006



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)


Non-BlacksAmlodipine/Chlorthalidone


Favors Amlodipine Favors Chlorthalidone

0.50 1 2

ALLHAT

7/27/2006



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)


Non-BlacksLisinopril/Chlorthalidone


Favors Lisinopril Favors Chlorthalidone

0.50 1 2

ALLHAT

7/27/2006 outcomes in hypertensive black and nonblack patients treated with chlorthalidone,...

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