blood pressure control by randomized drug group in allhat william c. cushman, charles e. ford, paula...

Blood Pressure Control Blood Pressure Control

By Randomized Drug By Randomized Drug

Group In ALLHATGroup In ALLHAT

William C. Cushman, Charles E. William C. Cushman, Charles E. Ford, Paula T. Einhorn, Jackson T. Ford, Paula T. Einhorn, Jackson T.

Wright, Jr., Richard A. Preston, Wright, Jr., Richard A. Preston, Barry R. Davis, and Jan N. Basile Barry R. Davis, and Jan N. Basile

for the ALLHAT Collaborative for the ALLHAT Collaborative Research GroupResearch Group

ALLHATALLHAT

Disclosure InformationDisclosure Information

William C. Cushman, William C. Cushman, MDMDThe following relationships exist that may be The following relationships exist that may be

related to this presentation:related to this presentation:

Research/grant support:Research/grant support: Astra-Zeneca, Kos, Astra-Zeneca, Kos, Aventis Pharma, King Pharmaceuticals, Aventis Pharma, King Pharmaceuticals, Boehringer-Ingelheim, Sanofi, BMS, Biovail, Boehringer-Ingelheim, Sanofi, BMS, Biovail, AbbottAbbott

Consultant and/or lectures:Consultant and/or lectures: Sanofi, Novartis, Sanofi, Novartis, Pfizer, Sankyo, Forest, Biovail, Abbott, Reddy, Pfizer, Sankyo, Forest, Biovail, Abbott, Reddy, First HorizonFirst Horizon

Others (stock, etc):Others (stock, etc): NoneNone

The Antihypertensive and The Antihypertensive and Lipid-Lowering Treatment to Lipid-Lowering Treatment to Prevent Heart Attack Trial Prevent Heart Attack Trial

(ALLHAT)(ALLHAT)Sponsored by the National Heart, Sponsored by the National Heart,

Lung, and Blood Institute Lung, and Blood Institute (NHLBI) in Collaboration with the (NHLBI) in Collaboration with the Department of Veterans Affairs Department of Veterans Affairs

(VA)(VA)www.allhat.orgwww.allhat.org

90% previously treated10% untreated

42,418 high-riskhypertensive patients

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

Atenolol28.0%

Clonidine10.6%

Reserpine4.3%

Hydralazine10.9%

Hypertension TrialHypertension TrialALLHAT

STEP 2 AND 3 AGENTSSTEP 2 AND 3 AGENTS

STEP 1 AGENTS (Double-blind)STEP 1 AGENTS (Double-blind)

90% previously treated10% untreated

42,418 high-riskhypertensive patients

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 AGENTSSTEP 2 AND 3 AGENTS

Atenolol28.0%

Clonidine10.6%

Reserpine4.3%

Hydralazine10.9%

Hypertension TrialHypertension TrialALLHAT

STEP 1 AGENTS (Double-blind)STEP 1 AGENTS (Double-blind)

Inclusion CriteriaInclusion Criteria

Men and women aged Men and women aged >> 55 years 55 years

Seated blood pressure (2 categories):Seated blood pressure (2 categories):

1) Treated for @ least 2 months:1) Treated for @ least 2 months:

BP BP <<160/100 mm Hg160/100 mm Hg

2) Not on drugs or on drugs < 2 months:2) Not on drugs or on drugs < 2 months:

SBP 140-180 mm Hg or DBP 90-110 mm HgSBP 140-180 mm Hg or DBP 90-110 mm Hg

Additional risk factor or target organ damage.Additional risk factor or target organ damage.

ALLHATALLHAT

Baseline Baseline CharacteristicsCharacteristics

CC AA LL AllAll

Sample SizeSample Size 15,25515,255 9,0489,048 9,0549,054 33,35733,357

Mean SBP/DBPMean SBP/DBP 145 / 83145 / 83 145 / 83145 / 83 145 / 83145 / 83 145 / 83145 / 83

Mean age, yearsMean age, years 6767 6767 6767 6767

Black, %Black, % 3535 3636 3535 3535

Women, %Women, % 4747 4747 4646 4747

Current smoking %Current smoking % 2222 2222 2222 2222

ASCVD, %ASCVD, % 4747 4646 4747 4747

Type II diabetes, %Type II diabetes, % 3636 3737 3535 3636

LVH by ECG, %LVH by ECG, % 33 33 33 33

Mean BMI, kg/mMean BMI, kg/m22 3030 3030 3030 3030

ALLHATALLHAT

144.8

134.1134.0134.9136.0136.8138.6

145.0

136.0135.7136.7

138.5140.0

141.9

83.2

74.775.876.477.878.780.0 75.576.777.478.779.9

81.283.4

0 12 24 36 48 60

Mean Systolic and Diastolic BP by Mean Systolic and Diastolic BP by Treatment Group Over TimeTreatment Group Over Time

Months of Follow-up

mm Hg

ALLHATALLHAT

70

75

80

85

90

135

140

145

150

~~

Systolic BPSystolic BP

Diastolic BPDiastolic BP

ChlorthalidoneChlorthalidone

AmlodipineAmlodipine

LisinoprilLisinopril

Percentage of Participants Percentage of Participants Receiving Blinded Study Drug or Receiving Blinded Study Drug or

Same ClassSame Class

888888899091 888888899092

8188

82 82 8185

0

20

40

60

80

100

6 12 24 36 48 60

Months of Follow-up

Per

cen

t

ALLHATALLHAT

ChlorthalidoneChlorthalidone AmlodipineAmlodipine LisinoprilLisinopril

Number of Antihypertensive Drugs Used Number of Antihypertensive Drugs Used and BP Control (<140/90 mm Hg)and BP Control (<140/90 mm Hg)

6867646158

53

28

6665635755

48

28

626359545146

27

1.9-2.11.8-2.0

1.7-1.81.5-1.7

1.4-1.51.3

0

20

40

60

80

100

0 6 12 24 36 48 60

Months of Follow-up

Per

cen

t

0

0.5

1

1.5

2

ALLHATALLHAT




BP Control (<140/90 mm Hg) and BP Control (<140/90 mm Hg) and Mean BP by Randomized Group and Mean BP by Randomized Group and

Race at 5 YearsRace 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

ALLHATALLHAT

0%

20%

40%

60%

80%

100%

Not on Drugs On 1 Drug On 2 Drugs On 3 Drugs On 4+ Drugs

Number of Antihypertensive Number of Antihypertensive Drugs PrescribedDrugs Prescribed

Months of Follow-UpMonths of Follow-Up

Per

cen

tP

erce

nt

ALLHATALLHAT

1212 3636 6060

CC CC CCAA AA AALL LL LL

Percent Controlled (BP < 140/90) Percent Controlled (BP < 140/90) at Five Years by Number of Drugs at Five Years by Number of Drugs

PrescribedPrescribed

68

3

11

2428

66

411

24 26

61

612

1824

0

10

20

30

40

50

60

70

80

1 2 3 4+ ALL

Number of Prescribed Drugs

Per

cen

tALLHATALLHAT




Cumulative Percent Controlled (BP Cumulative Percent Controlled (BP < 140/90) at Five Years by < 140/90) at Five Years by

Number of Drugs PrescribedNumber of Drugs Prescribed

63

52

28

1

61

50

1

24

54

42

24

2

0

10

20

30

40

50

60

70

0 1 1 or 2 1, 2, or 3

Number of Prescribed Drugs

Per

cen

tALLHATALLHAT




Number of Drugs Needed to Control BP Number of Drugs Needed to Control BP (<140/90 mm Hg) in ALLHAT After 5 Years(<140/90 mm Hg) in ALLHAT After 5 Years

• 26% of participants were controlled on 1 drug 26% of participants were controlled on 1 drug (another 2% were untreated):(another 2% were untreated): therefore, at least 72% received or needed ≥ 2 therefore, at least 72% received or needed ≥ 2

drugs.drugs.

• 49% were controlled on 1 or 2 drugs (12% more 49% were controlled on 1 or 2 drugs (12% more were uncontrolled on 1 drug or untreated): were uncontrolled on 1 drug or untreated): therefore, at least 39% received or would therefore, at least 39% received or would

have needed ≥ 3 drugs to control BP.have needed ≥ 3 drugs to control BP.

• 60% were controlled on 3 or fewer drugs:60% were controlled on 3 or fewer drugs: therefore, at least 16% received or needed ≥ 4 therefore, at least 16% received or needed ≥ 4

drugs to control BP.drugs to control BP.

ALLHATALLHAT

Conclusions - 1Conclusions - 1

BP was well controlled in the BP was well controlled in the

majority of participants in ALLHAT.majority of participants in ALLHAT.

Average BP was well below 140/90 Average BP was well below 140/90

mm Hg for participants in each mm Hg for participants in each

randomized group.randomized group.

More participants were controlled More participants were controlled

with chlorthalidone than the other with chlorthalidone than the other

two agents as monotherapy.two agents as monotherapy.

ALLHATALLHAT

However, <30% of participants could be However, <30% of participants could be controlled on any of the drugs as a single controlled on any of the drugs as a single agent. agent.

At least 2 medications were required for At least 2 medications were required for most participants to achieve BP control. most participants to achieve BP control.

These ALLHAT data support the These ALLHAT data support the recommendations of JNC 7 promoting recommendations of JNC 7 promoting multidrug regimens and the initial multidrug regimens and the initial selection of thiazide-type diuretics for selection of thiazide-type diuretics for most patients to improve BP control most patients to improve BP control rates.rates.

Conclusions - 2Conclusions - 2ALLHATALLHAT

BMI BMI ≥ 30 kg/m≥ 30 kg/m22

Factors Related to Blood Pressure Factors Related to Blood Pressure Control at 36 Months of Follow-upControl at 36 Months of Follow-up

ChlorthalidoneChlorthalidone AmlodipineAmlodipine

ALLHATALLHAT

Prior BP TreatmentPrior BP Treatment

SmokerSmoker

Type II Type II DiabeticDiabetic

nonBlacknonBlack

Age Per Decade Age Per Decade ↑↑

Baseline SBP Baseline SBP (10 mm Hg (10 mm Hg ↑)↑)

Cr Cr ≥ 1.5 mg/dL≥ 1.5 mg/dL

MaleMale

BP Control BP Control BP Control BP Control Worse BetterWorse Better

0.500.50 11 22

0.80 (0.78, 0.83)

0.93 (0.88, 0.98)

1.10 (1.02, 1.20)

1.28 (1.17, 1.39)

0.88 (0.81, 0.96)

1.03 (0.93, 1.14)

0.87 (0.80, 0.95)

0.69 (0.60, 0.80)

0.79 (0.67, 0.94)


0.500.50 11 22

0.81 (0.78, 0.84)

0.91 (0.84, 0.98)

0.98 (0.88, 1.09)

1.56 (1.39, 1.74)

0.83 (0.74, 0.92)

0.96 (0.84, 1.09)

0.88 (0.79, 0.98)

0.66 (0.55, 0.81)

0.83 (0.65, 1.07)

Prior BP TreatmentPrior BP Treatment

BMI BMI ≥ 30 kg/m≥ 30 kg/m22

SmokerSmoker

Type II DiabeticType II Diabetic

nonBlacknonBlack

Age Per Decade Age Per Decade ↑↑

Factors Related to Blood Pressure Factors Related to Blood Pressure Control at 36 Months of Follow-upControl at 36 Months of Follow-up

ChlorthalidoneChlorthalidone LisinoprilLisinopril

ALLHATALLHAT

Baseline SBP Baseline SBP (10 mm Hg (10 mm Hg ↑)↑)

Cr Cr ≥ 1.5 mg/dL≥ 1.5 mg/dL

MaleMale


0.500.50 11 22

0.80 (0.78, 0.83)

0.93 (0.88, 0.98)

1.10 (1.02, 1.20)

1.28 (1.17, 1.39)

0.88 (0.81, 0.96)

1.03 (0.93, 1.14)

0.87 (0.80, 0.95)

0.69 (0.60, 0.80)

0.79 (0.67, 0.94)


0.500.50 11 22

0.78 (0.75, 0.81)

0.89 (0.83, 0.96)

1.19 (1.07, 1.33)

1.56 (1.39, 1.75)

0.89 (0.80, 1.00)

0.93 (0.81, 1.06)

0.91 (0.81, 1.01)

0.62 (0.51, 0.75)

0.91 (0.72, 1.15)

Multiple Logistic Regression Analysis: Multiple Logistic Regression Analysis: Relative Odds (95% CI) of Relative Odds (95% CI) of BP ControlBP Control at 36 Monthsat 36 Months

ALLHATALLHAT

BP Control Better

0.5 0.6 0.7 0.8 0.9 1 1.1 1.2

Age (10 year Age (10 year ↑) ↑)

Baseline SBP (10 mmHg Baseline SBP (10 mmHg ↑)↑) **

MaleMale **BlackBlack

Type 2 DiabeticType 2 Diabetic

SmokerSmoker ASCVDASCVD **

BMI BMI ≥ 30 kg/m≥ 30 kg/m22 **Prior RxPrior Rx **Cr Cr ≥ 1.5 mg/dL≥ 1.5 mg/dL **ECG LVHECG LVH **Clinic Research Exp.Clinic Research Exp. **

BP Control WorseMoreMore ( (**) or) or lessless ( () likely to be ) likely to be on 2+ drugson 2+ drugs

Cushman, et al. J Clinical Hypertens 2002; 4:393-404Cushman, et al. J Clinical Hypertens 2002; 4:393-404

Logistic Regression Analysis of Logistic Regression Analysis of Relative Odds (95% CI) of Relative Odds (95% CI) of Being On 2+ Being On 2+ DrugsDrugs at 36 Months at 36 Months

ALLHATALLHAT

Age (10 year Age (10 year ↑)↑)

BlackBlack

SmokerSmoker

Prior RxPrior Rx

0.7 0.9 1.1 1.3 1.5 1.7 1.9 2.1 2.3

More Likely To Be On 2+ Drugs

Baseline SBP (10 mmHg Baseline SBP (10 mmHg ↑)↑)

MaleMale

Type 2 DiabeticType 2 Diabetic

ASCVDASCVD

BMI BMI ≥ 30 kg/m2≥ 30 kg/m2

Cr Cr ≥ 1.5 mg/dL≥ 1.5 mg/dLECG LVHECG LVHClinic Research Exp.Clinic Research Exp.

Less Likely To Be On 2+ Drugs

Cushman, et al. J Clinical Hypertens 2002; 4:393-404Cushman, et al. J Clinical Hypertens 2002; 4:393-404

BP Control (<140/90 mm Hg) by BP Control (<140/90 mm Hg) by Randomized Group and RaceRandomized Group and Race

59 5651

66 6763

555860

42

5054

656870

54

6264

0

20

40

60

80

Chlor Amlo Lisin Chlor Amlo Lisin

1 year 3 years 5 years

BlackBlack Non-BlackNon-Black

Number of Drugs Needed to Control BP Number of Drugs Needed to Control BP (<140/90 mm Hg) in ALLHAT After 5 Years(<140/90 mm Hg) in ALLHAT After 5 YearsALLHATALLHAT

No. of No. of DrugsDrugs


N = 5670N = 5670


N = 3400N = 3400


N = 3191N = 3191

ALLALL

N = 12,261N = 12,261

<140/90<140/90 ≥≥140/90140/90 <140/90<140/90 ≥≥140/90140/90 <140/90<140/90 ≥≥140/90140/90 <140/90<140/90 ≥≥140/90140/90

00 1.31.3 0.70.7 1.01.0 0.60.6 1.71.7 0.60.6 1.31.3 0.70.7

11 28.128.1 9.69.6 24.124.1 9.89.8 23.923.9 9.49.4 25.925.9 9.69.6

1 or 1 or 22 52.452.4 21.521.5 49.749.7 22.622.6 41.841.8 21.521.5 48.948.9 21.821.8

1 - 1 - 33 63.163.1 28.428.4 60.960.9 29.729.7 53.753.7 31.731.7 60.060.0 29.629.6

1 - 4+1 - 4+ 66.566.5 31.531.5 65.265.2 33.233.2 59.459.4 38.338.3 64.364.3 33.833.8

TotalTotal 67.867.8 32.232.2 66.266.2 33.833.8 61.161.1 38.938.9 65.665.6 34.434.4

blood pressure control by randomized drug group in allhat william c. cushman, charles e. ford, paula...

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