success and predictors of blood pressure control in diverse north american settings: the...

Success and Predictors of Success and Predictors of Blood Blood

Pressure ControlPressure Control in Diverse North in Diverse North

American Settings: The American Settings: The

Antihypertensive and Lipid-lowering Antihypertensive and Lipid-lowering

Treatment to Prevent Heart Attack Treatment to Prevent Heart Attack

Trial (ALLHAT)Trial (ALLHAT)William C Cushman, MD, Charles E Ford, William C Cushman, MD, Charles E Ford,

PhD, Jeffrey A Cutler, MD, Karen L Margolis, PhD, Jeffrey A Cutler, MD, Karen L Margolis, MD, MPH, Barry R Davis, MD, PhD, et al, for MD, MPH, Barry R Davis, MD, PhD, et al, for

the the

ALLHAT Collaborative Research GroupALLHAT Collaborative Research Group

J Clinical Hypertens 2002; 4:393-404J Clinical Hypertens 2002; 4:393-404

ALLHATALLHAT

NHANES III: NHANES III: 27% for adults with hypertension.27% for adults with hypertension. Among those Among those on treatmenton treatment in NHANES III: in NHANES III:

30 to 45% in older adults from various sex-30 to 45% in older adults from various sex-race/ethnicity groups.race/ethnicity groups.

In treated patients in Olmstead County, MN:In treated patients in Olmstead County, MN: 33% among persons 45 years and older.33% among persons 45 years and older.

At a group of New England Veterans Affairs At a group of New England Veterans Affairs Medical Centers:Medical Centers: < 25% in older (mostly white) males< 25% in older (mostly white) males

Blood Pressure Control (<140/90 mm Hg) Blood Pressure Control (<140/90 mm Hg) Rates in The United States in the 1990sRates in The United States in the 1990s

Burt, et al. Burt, et al. HypertensionHypertension 1995;25:305-13. 1995;25:305-13.Meissner, et al. Meissner, et al. HypertensionHypertension 1999;34:466-71. 1999;34:466-71.Berlowitz, et alBerlowitz, et alN Engl J MedN Engl J Med 1998;339:1957-63. 1998;339:1957-63.

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)

ALLHATALLHAT

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.

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

Additional risk factor or target organ Additional risk factor or target organ

damage.damage.

ALLHATALLHAT

ALLHAT BP Eligibility ALLHAT BP Eligibility CriteriaCriteria

Lower Limit (mm Hg)

Upper Limit (mm Hg)

Status at Visit 1 and Visit 2 SBP DBP SBP DBP

On 1-2 drugs used for hypertension >= 2 months

Visit 1 Visit 2

---

---

---

---

160

180

100

110

On drugs for < 2 months or currently untreated

Visit 1 & Visit 2

140 90 180 110

SBP or DBP lower limit must be met at Visit 1 and Visit 2 SBP and DBP upper limit must be met at Visit 1 and Visit 2

ALLHATALLHAT

Baseline Baseline CharacteristicsCharacteristics

Sample SizeSample Size 33,35733,357

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

Mean age, yearsMean age, years 6767

Black, %Black, % 3535

Women, %Women, % 4747

Current smoking %Current smoking % 2222

ASCVD, %ASCVD, % 4747

Type II diabetes, %Type II diabetes, % 3636

LVH by ECG, %LVH by ECG, % 33

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

ALLHATALLHAT

Baseline CharacteristicsBaseline Characteristics

Serum Creatinine, mg/dLSerum Creatinine, mg/dL 1.021.02

Fasting Glucose, mg/dLFasting Glucose, mg/dL 125125

Total Cholesterol, mg/dLTotal Cholesterol, mg/dL 216216

LDL-Cholesterol, mg/dLLDL-Cholesterol, mg/dL 136136

HDL-Cholesterol, mg/dLHDL-Cholesterol, mg/dL 4747

Triglycerides, mg/dLTriglycerides, mg/dL 172172

ALLHATALLHAT

Antihypertensive Treatment Antihypertensive Treatment RegimenRegimen

Step 1Step 1 Dose 1Dose 1 Dose 2Dose 2 Dose 3Dose 3

ChlorthalidoneChlorthalidone 12.5 mg12.5 mg 12.5 mg12.5 mg 25 mg25 mg

AmlodipineAmlodipine 2.5 mg2.5 mg 5 mg5 mg 10 mg10 mg

LisinoprilLisinopril 10 mg10 mg 20 mg20 mg 40 mg40 mg

Step 2Step 2

ReserpineReserpine 0.05 mg qd0.05 mg qd 0.1 mg qd0.1 mg qd 0.2 mg qd0.2 mg qd

ClonidineClonidine 0.1 mg bid0.1 mg bid 0.2 mg bid0.2 mg bid 0.3 mg bid0.3 mg bid

AtenololAtenolol 25 mg qd25 mg qd 50 mg qd50 mg qd 100 mg qd100 mg qd

Step 3Step 3

HydralazineHydralazine 25 mg bid25 mg bid 50 mg bid50 mg bid 100 mg bid100 mg bid

ALLHATALLHAT

140137

145

138136 135 135

8381 79 78 77 76 75

0 12 24 36 48 60

Mean Systolic and Mean Systolic and Diastolic Blood PressureDiastolic Blood Pressure

Months of Follow-up

mm Hg

ALLHATALLHAT

70

75

80

85

90

135

140

145

150

~~

Systolic BPSystolic BP

Diastolic BPDiastolic BP

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

BP Results by Treatment GroupBP Results by Treatment Group

Compared to chlorthalidone:

SBP significantly higher in the amlodipine group (~1 mm Hg) and the lisinopril group (~2 mm Hg).

Compared to chlorthalidone:

DBP significantly lower in the amlodipine group (~1 mm Hg).

ALLHAT

JAMA 2002;288:2981-2997JAMA 2002;288:2981-2997

BLBL 6M6M 1Y1Y 3Y3Y 5Y5Y

CC 146.2146.2 138.2138.2 136.6136.6 134.6134.6 134.1134.1

AA 146.2146.2 140.0140.0 138.3138.3 135.4135.4 134.9134.9

LL 146.4146.4 141.4141.4 139.7139.7 136.4136.4 136.1136.1

BLBL 6M6M 1Y1Y 3Y3Y 5Y5Y

CC 84.084.0 80.180.1 79.279.2 77.177.1 75.475.4

AA 83.983.9 79.779.7 78.578.5 76.176.1 74.574.5

LL 84.184.1 80.880.8 79.779.7 77.277.2 75.475.4

SBP Distribution at Baseline SBP Distribution at Baseline and 36 Months of Follow-upand 36 Months of Follow-up

0

10

20

30

40

<100 100-109

110-119

120-129

130-139

140-149

150-159

160-169

170-179

180+

Baseline:Baseline:31% <31% < 140 mm Hg 140 mm Hg14% 14% 160 mm Hg 160 mm Hg

36 Months:36 Months:64% <64% < 140 mm Hg 140 mm Hg 8% 8% 160 mm Hg 160 mm Hg

SBP (mm Hg)

Per

cen

t

ALLHATALLHAT


DBP Distribution at Baseline DBP Distribution at Baseline and 36 Months of Follow-upand 36 Months of Follow-up

0

10

20

30

<65 65-69

70-74

75-79

80-84

85-89

90-94

95-99

100-104

105+

BaselineBaseline68% < 90 mm Hg68% < 90 mm Hg 4% 4% ≥ 100 mm Hg≥ 100 mm Hg

36 Months36 Months90% < 90 mm Hg90% < 90 mm Hg 2% 2% ≥ 100 mm Hg≥ 100 mm Hg

DBP (mm Hg)

Per

cen

t

ALLHATALLHAT


Blood Pressure ControlBlood Pressure Control

31

58 60 64 67 67

92%91%90%88%86%

68% 6665625855

27

0

20

40

60

80

100

0 1 2 3 4 5

Years of Follow-up

Per

cen

t

DBP<90 SBP<140 BP<140/90

ALLHATALLHAT



SBP Distribution at 36 SBP Distribution at 36 Months of Follow-upMonths of Follow-up

0.52.4

9.1

20.9

31.5

19

8.5

4.61.9 1.6

0

10

20

30

40

<100 100-109

110-119

120-129

130-139

140-149

150-159

160-169

170-179

180+

64% <64% < 140 mm Hg 140 mm Hg36% 36% 140 mm Hg 140 mm Hg 8% 8% 160 mm Hg 160 mm Hg

Of those Of those 140 mm Hg: 140 mm Hg:53% 140-149 mm Hg53% 140-149 mm Hg24% 150-159 mm Hg24% 150-159 mm Hg(77% 140-159 mm Hg)(77% 140-159 mm Hg)

SBP (mm Hg)

Per

cen

t

ALLHATALLHAT


BP Control (<140/90 mm Hg) at 5 BP Control (<140/90 mm Hg) at 5 Years by Randomized GroupYears by Randomized Group

68 6661

0

20

40

60

80

Chlorthalidone Amlodipine Lisinopril

Pe

rce

nt

JAMA 2002;288:2981-2997JAMA 2002;288:2981-2997


31

58 60 64 67 67

92%91%90%88%86%

68% 66656258

27

55

0

20

40

60

80

100

0 1 2 3 4 5

Years of Follow-up

Per

cen

t

DBP<90 SBP<140 BP<140/90

ALLHATALLHAT

1.41.6 1.7 1.8

2.0

1.6 = mean number of drugs= mean number of drugs


0

20

40

60

80

100

0 12 24 36 48 60

Use of Blinded (Step 1) Drug and Use of Blinded (Step 1) Drug and Number of Antihypertensive Drugs Number of Antihypertensive Drugs PrescribedPrescribed

Months of Follow-Up

Per

cen

tALLHATALLHAT

On Step 1 DrugOn Step 1 Drug

On 1 DrugOn 1 Drug

On 2 DrugsOn 2 Drugs

On 3 DrugsOn 3 Drugs

On 4+ DrugsOn 4+ Drugs

@ 5 years:@ 5 years: 62% were on 62% were on >>2 drugs, 30% were 2 drugs, 30% were on 1 drug with BP <140/90 mm Hgon 1 drug with BP <140/90 mm Hg Cushman, et al. J Clinical Hypertens 2002; 4:393-404Cushman, et al. J Clinical Hypertens 2002; 4:393-404

Proportion of Uncontrolled Proportion of Uncontrolled ALLHAT Participants ALLHAT Participants NotNot

Stepped Up at Annual VisitsStepped Up at Annual Visits

5968 69 72 72

0

20

40

60

80

1 2 3 4 5

Years

Pe

rce

nt


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


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


Relative Odds (95% CI) of Relative Odds (95% CI) of BP ControlBP Control or or Being Being On 2+ DrugsOn 2+ Drugs at 36 Months of Follow-Up, by at 36 Months of Follow-Up, by Geographic Region (Compared with Geographic Region (Compared with WestWest))

ALLHATALLHAT

0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2

More Likely To Be On 2+ Drugs

MidwestMidwestEastEast

SouthSouthCanadaCanada

Puerto Rico/VIPuerto Rico/VI

EastEast

SouthSouthCanadaCanada

Puerto Puerto Rico/VIRico/VI

MidwestMidwest

Less Likely To Be On 2+ Drugs

BP Control BetterBP Control Worse


Other Large Trials and BP Other Large Trials and BP ControlControl

LIFE (4.8 years of f/u):LIFE (4.8 years of f/u):46%: atenolol arm 46%: atenolol arm 49%: losartan arm49%: losartan arm

CONVINCE (30 and 36 months CONVINCE (30 and 36 months of f/u):of f/u):67% overall and similar in 67% overall and similar in

verapamil HS and standard verapamil HS and standard therapy armstherapy arms

Conclusions - 1Conclusions - 1The ALLHAT trial provides compelling The ALLHAT trial provides compelling

evidence that BP control rates can be evidence that BP control rates can be markedly increased to at least 2/3 of markedly increased to at least 2/3 of the treated hypertensive population. the treated hypertensive population.

These control rates were achieved in a These control rates were achieved in a multiethnic hypertensive population in multiethnic hypertensive population in diverse practice settings.diverse practice settings.

Most of the participants who did not Most of the participants who did not achieve goal had persistent elevation achieve goal had persistent elevation of SBP. of SBP.

ALLHATALLHAT

At least 2 antihypertensive At least 2 antihypertensive medications are required for most medications are required for most patients to achieve BP control.patients to achieve BP control.

Various factors that are associated Various factors that are associated with lower BP control rates were with lower BP control rates were identified. identified.

It is likely that the majority of people It is likely that the majority of people with hypertension could achieve BP < with hypertension could achieve BP < 140/90 mm Hg with the 140/90 mm Hg with the antihypertensive medications antihypertensive medications available today.available today.

ALLHATALLHAT Conclusions - 2Conclusions - 2

26

BP Inadequately ControlledBP Inadequately Controlled†† in Nearly 75% in Nearly 75%of Adult Hypertensivesof Adult Hypertensives** in the US in the US

68%68%

54%54%

27%27%

†† SBP <140 mm Hg and DBP <90 mm Hg.SBP <140 mm Hg and DBP <90 mm Hg.NHANES = National Health and Nutrition Examination Surveys.NHANES = National Health and Nutrition Examination Surveys.

•Age 18 to 74 years with SBP 140 mm Hg or DBP 90 mm Hg or taking antihypertensive medication.Age 18 to 74 years with SBP 140 mm Hg or DBP 90 mm Hg or taking antihypertensive medication.

JNC VI. JNC VI. Arch Intern MedArch Intern Med. 1997;157:2413-46.. 1997;157:2413-46.

NHANES IIINHANES III(Phase 2)(Phase 2)1991-19941991-1994

NHANES IIINHANES III(Phase 1)(Phase 1)1988-19911988-1991

73%73%

55%55%

29%29%

NHANES IINHANES II

1976-19801976-1980

51%51%

31%31%

10%10%

AwareAware

TreatedTreated

ControlledControlled††

• Participants were randomized to Participants were randomized to chlorthalidonechlorthalidone

(15,255), (15,255), amlodipineamlodipine (9,048), (9,048), lisinoprillisinopril (9,054), or (9,054), or

doxazosindoxazosin (9,061) between 2/94-1/98. [Sponsored (9,061) between 2/94-1/98. [Sponsored

by NHLBI]by NHLBI]

• Over 15,000 (>3000/drug group) of ALLHAT Over 15,000 (>3000/drug group) of ALLHAT

participants had DM at baseline and a similar # participants had DM at baseline and a similar #

were African Americans.were African Americans.

• The The doxazosindoxazosin arm was stopped in January 2000 arm was stopped in January 2000

due to higher CV events and virtually no chance to due to higher CV events and virtually no chance to

show a difference in CHD.show a difference in CHD.

• The remaining 3 arms continued to scheduled The remaining 3 arms continued to scheduled

completion and were reported in December 2002.completion and were reported in December 2002.

ALLHATALLHAT n=42,418n=42,418

ALLHATALLHAT

Inclusion Criteria - 2Inclusion Criteria - 2At least one of the following: At least one of the following:

• Myocardial infarction or stroke: age-Myocardial infarction or stroke: age-indeterminate or at least 6 months oldindeterminate or at least 6 months old

• History of revascularization procedureHistory of revascularization procedure

• Other documented ASCVDOther documented ASCVD

• Major ST segment depression or T-wave inversionMajor ST segment depression or T-wave inversion

• Type II diabetes mellitusType II diabetes mellitus

• HDL cholesterol < 35 mg/dl on any 2 or more HDL cholesterol < 35 mg/dl on any 2 or more determinations in past 5 yearsdeterminations in past 5 years

• Left ventricular hypertrophy (past 2 years) on ECG Left ventricular hypertrophy (past 2 years) on ECG or echoor echo

• Current cigarette smokingCurrent cigarette smoking

ALLHATALLHAT

Exclusion Criteria for Exclusion Criteria for Antihypertensive TrialAntihypertensive Trial

Angina pectoris or recent MI or Stroke (within past 6 Angina pectoris or recent MI or Stroke (within past 6 months)months)

Heart failure and/or LVEF < 35%, if knownHeart failure and/or LVEF < 35%, if known

Renal insufficiency (serum creatinine > 2.0 mg/dL)Renal insufficiency (serum creatinine > 2.0 mg/dL)

Requiring diuretics, calcium channel blockers, ACE Requiring diuretics, calcium channel blockers, ACE inhibitors, or alpha adrenergic blockers for reasons inhibitors, or alpha adrenergic blockers for reasons other than high other than high blood pressureblood pressure

Requiring more than two antihypertensive agents to Requiring more than two antihypertensive agents to achieve blood pressure controlachieve blood pressure control

Factors suggesting inability to comply with protocolFactors suggesting inability to comply with protocol

ALLHATALLHAT

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

1.3 1.41.6 1.7 1.8

2

0

20

40

60

80

100

0 6 12 24 36 48 60Months

% <

140/

90 m

m H

g

0

0.5

1

1.5

2

2.5

Nu

mb

er o

f D

rug

s

ALLHATALLHAT

66%66%

27%27%

50%50% 55%55% 58%58%62%62% 65%65%


success and predictors of blood pressure control in diverse north american settings: the...

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yearsseated blood pressure

blood pressure controlcushman

bp results

amlodipine group

months of followup baseline68

treatment groupcompared

older adults

lisinopril group