Improving the Care of the Improving the Care of the Hypertensive Patient:Hypertensive Patient:

US PerspectiveUS Perspective

William Cushman, MDWilliam Cushman, MDProfessor, Preventive Medicine and MedicineProfessor, Preventive Medicine and MedicineUniversity of Tennessee College of MedicineUniversity of Tennessee College of Medicine

Chief, Preventive MedicineChief, Preventive MedicineMemphis VA Medical CenterMemphis VA Medical Center

DISCLOSURE OF RELATIONSHIPS

For William C. Cushman, MD Over the Past 12 Months

Grant/Research support: Astra-Zeneca, Sanofi-

Aventis, King, GlaxoSmithKline, Novartis

Consultant: Sanofi-Aventis, BMS, Novartis, Pfizer,

Daiichi Sankyo, Forest, King Pharmaceuticals,

Boehringer-Ingelheim, Roche

Speakers Bureau: none

Major stock shareholder: none

Other Support, Tangible or intangible: none

25 2529 28

30

0

10

20

30

40

50

1988-91 1991-94 1999-2000 2001-02 2003-04

Prevalence of Hypertension in U.S.: Prevalence of Hypertension in U.S.: 1988-20041988-2004

70 million Americans70 million Americans

Prevalence of Hypertension in U.S.: Prevalence of Hypertension in U.S.: 1988-20041988-2004

70 million Americans70 million Americans

Po

pu

lati

on

Wit

h

Hyp

erte

nsi

on

(%

)

From Bernard CheungFrom Bernard CheungOng, et al, Hypertension 2007Ong, et al, Hypertension 2007

Increase in prevalence of HTN from 1988 to 1999;Increase in prevalence of HTN from 1988 to 1999;No significant increase between 1999 and 2004.No significant increase between 1999 and 2004.

25

5

27

58

30

7

33

66

0

20

40

60

80

All 18-39 40-59 60+

1988-91 1991-94 1999-2000 2001-02 2003-04

Prevalence of Hypertension in U.S.: Prevalence of Hypertension in U.S.:

1988-2004 1988-2004

Prevalence of Hypertension in U.S.: Prevalence of Hypertension in U.S.:

1988-2004 1988-2004

Po

pu

lati

on

Wit

h

Hyp

erte

nsi

on

(%

)

From Bernard CheungFrom Bernard CheungOng, et al, Hypertension 2007Ong, et al, Hypertension 2007

2629

17

29

39

28

0

10

20

30

40

50

Non-Hisp White Non-Hisp Black Mex Amer

1988-91 1991-94 1999-2000 2001-02 2003-04

Prevalence of Hypertension in U.S. Prevalence of Hypertension in U.S. by Race/Ethnicity: by Race/Ethnicity:

1988-2004 1988-2004

Prevalence of Hypertension in U.S. Prevalence of Hypertension in U.S. by Race/Ethnicity: by Race/Ethnicity:

1988-2004 1988-2004

Po

pu

lati

on

Wit

h

Hyp

erte

nsi

on

(%

)

From Bernard CheungFrom Bernard CheungOng, et al, Hypertension 2007Ong, et al, Hypertension 2007

51

7368 70

31

55 5459

10

29 2734

0

20

40

60

80

100

1976-80 1988-91 1991-94 1999-2000

Per

cen

t o

f H

TN

Po

pu

lati

on

Awareness Treatment Control

Awareness, Treatment and Control in Adults Awareness, Treatment and Control in Adults Ages Ages 18-74 Yrs18-74 Yrs with Hypertension in US with Hypertension in US

NHANES NHANES 1976-20001976-2000

Chobanian et al. Chobanian et al. JAMAJAMA. 2003;289:2560-2572.. 2003;289:2560-2572.

69 7176

58 6065

29 33 37

0

20

40

60

80

100

1999-2000 2001-2002 2003-2004

Per

cen

t o

f H

TN

Po

pu

lati

on

Awareness Treatment Control

Awareness, Treatment and Control in (Awareness, Treatment and Control in (AllAll) ) Adults with Hypertension in US NHANES Adults with Hypertension in US NHANES

1999-20041999-2004

Not adjusted for age.Not adjusted for age.*P<0.05 compared to 1999-2000.*P<0.05 compared to 1999-2000.

From Bernard CheungFrom Bernard CheungOng, et al, Hypertension 2007Ong, et al, Hypertension 2007

*

*

NHANES 1999-2004NHANES 1999-2004ConclusionsConclusions

• HTN prevalence HTN prevalence from 1988-1999, but no from 1988-1999, but no significant significant in the prevalence of HTN between in the prevalence of HTN between 1999 and 2004.1999 and 2004.

• From 1999 to 2004: BP control in HTN From 1999 to 2004: BP control in HTN (to 37%). (to 37%).

• Improvement in BP control observed in both Improvement in BP control observed in both sexes, in non-Hispanic black and Mexican sexes, in non-Hispanic black and Mexican Americans.Americans.

• In the young, awareness and treatment rates are In the young, awareness and treatment rates are low, but BP is easy to control.low, but BP is easy to control.

• In the elderly, awareness and treatment rates are In the elderly, awareness and treatment rates are high, but BP targets are less easily reached.high, but BP targets are less easily reached.

From Bernard CheungFrom Bernard CheungOng, et al, Hypertension 2007Ong, et al, Hypertension 2007

Lifestyle Modification for Lifestyle Modification for Prevention in PreHTN and Prevention in PreHTN and

Treatment in HTNTreatment in HTN

ModificationApproximate SBP reduction (range)

Weight reduction 5-20 mmHg / 10 kg weight loss

Adopt DASH eating plan 8-14 mmHg

Dietary sodium reduction 2-8 mmHg

Physical activity 4-9 mmHg

Moderation of alcohol consumption

2-4 mmHg

JNC 7. JAMA. 2003; 289:2560fJNC 7. JAMA. 2003; 289:2560f

90% previously treated90% previously treated10% untreated10% untreated

42,418 high-risk42,418 high-riskhypertensive patientshypertensive patients

ChlorthalidoneChlorthalidone12.5-25 mg12.5-25 mg

AmlodipineAmlodipine2.5-10 mg2.5-10 mg

LisinoprilLisinopril10-40 mg10-40 mg

DoxazosinDoxazosin1-8 mg1-8 mg

N=15,255N=15,255 N=9,048N=9,048 N=9,054N=9,054 N=9,061N=9,061

Hypertension TrialHypertension Trial

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

Blinded drugs titrated and atenolol, clonidine, reserpine, Blinded drugs titrated and atenolol, clonidine, reserpine, and/or hydralazine added as needed to achieve BP goal: and/or hydralazine added as needed to achieve BP goal: <140/90 mm Hg<140/90 mm Hg

ALLHAT

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

Blood Pressure ControlBlood Pressure Control

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

Percent

DBP<90 SBP<140 BP<140/90

1.41.41.61.6 1.71.7 1.81.8

2.02.0

2.0 = = mean number of drugs number of drugs

ALLHATALLHAT

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

26

49

66

0

20

40

60

80

1 1 or 2 Any

Number of Prescribed Drugs

Perc

ent

ALLHATALLHATCumulative Percent Controlled Cumulative Percent Controlled

(BP <140/90 mm Hg) at Five Years(BP <140/90 mm Hg) at Five Years

Derived from Cushman et al. J Clin Hypertens. 2002;Derived from Cushman et al. J Clin Hypertens. 2002;4:393-4044:393-404

Inadequate Management of BP in a Inadequate Management of BP in a VA Hypertensive PopulationVA Hypertensive Population

800 hypertensive men @ 5 VAs in New England over a 800 hypertensive men @ 5 VAs in New England over a 2 yr period in early 1990s.2 yr period in early 1990s.

>6 HTN-related MD visits/yr; ave age: 65.5 years.>6 HTN-related MD visits/yr; ave age: 65.5 years. BP control:BP control:

40% had BP 40% had BP >>160/90 mm Hg160/90 mm Hg <25% had BP <140/90 mm Hg<25% had BP <140/90 mm Hg Increases in therapy: only 6.7% of visits.Increases in therapy: only 6.7% of visits.

More intensive Tx lead to better control of BP (p<.01).More intensive Tx lead to better control of BP (p<.01). ““Many physicians are not aggressive enough in their Many physicians are not aggressive enough in their

approach to hypertension.”approach to hypertension.”

Berlowitz, et al: NEJM 1998;339:1957-63Berlowitz, et al: NEJM 1998;339:1957-63

Response to Berlowitz, et al, Response to Berlowitz, et al, Article and Other Changes in VAArticle and Other Changes in VA

• BP control rates were made a BP control rates were made a performance performance measuremeasure: audited by Office of Quality : audited by Office of Quality Performance (OQP) as part of the External Peer Performance (OQP) as part of the External Peer Review Program (EPRP).Review Program (EPRP).

• Electronic medical record systemElectronic medical record system VA-wide since VA-wide since 1997-98.1997-98.

• Clinical reminderClinical reminder in electronic medical record if in electronic medical record if BP above goal.BP above goal.

• VA HTN Field Advisory Committee conducted a VA HTN Field Advisory Committee conducted a series of national series of national teleconferencesteleconferences: ALLHAT, JNC : ALLHAT, JNC 7, VA-DoD HTN guidelines, BP and thiazide 7, VA-DoD HTN guidelines, BP and thiazide diuretic performance measures, et al.diuretic performance measures, et al.

Outpatient hypertension treatment, Outpatient hypertension treatment, treatment intensification, and control in treatment intensification, and control in

Western Europe and the United States Western Europe and the United States

4640

31

4036

63

15 1621 20

28

38

53 5559 59

44

64

0

10

20

30

40

50

60

70

France Germany Italy Spain UK US

HTN Control Med increase if uncontrolled 2+ AHT classes

Wang, et al. Arch Int Med 2007;176:141-7

Cross-sectional analyses of the nationally representative CardioMonitor 2004 Cross-sectional analyses of the nationally representative CardioMonitor 2004 survey: 291 cardiologist and 1284 PCPs (n=21,053 hypertensive patients)survey: 291 cardiologist and 1284 PCPs (n=21,053 hypertensive patients)

JNC 7 Algorithm for JNC 7 Algorithm for Treatment of Treatment of HypertensionHypertension

Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease)

Initial Drug Choices

Drug(s) for the compelling indications

Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB)

as needed.

With Compelling Indications

Lifestyle Modifications

Stage 2 Hypertension (SBP >160 or DBP >100 mmHg)

2-drug combination for most (usually thiazide-type diuretic and

ACEI, or ARB, or BB, or CCB)

Stage 1 Hypertension(SBP 140–159 or DBP 90–99

mmHg) Thiazide-type diuretics for most.

May consider ACEI, ARB, BB, CCB,

or combination.

Without Compelling Indications

Not at Goal Blood Pressure

Optimize dosages or add additional drugs until goal blood pressure is achieved.

Consider consultation with hypertension specialist.

JNC 7. JAMA. 2003; 289:2560fJNC 7. JAMA. 2003; 289:2560f

Recommendation for Initial Antihypertensive Drug Therapy in JNC 7

Thiazide-type diuretics should be used as initial therapy Thiazide-type diuretics should be used as initial therapy for most patients, either alone or in combination with one for most patients, either alone or in combination with one of the other classes (ACEIs, ARBs, BBs, CCBs) that have of the other classes (ACEIs, ARBs, BBs, CCBs) that have also been shown to reduce one or more hypertensive also been shown to reduce one or more hypertensive complications in randomized controlled outcome trials.complications in randomized controlled outcome trials.

Selection of one of these other agents as initial therapy is Selection of one of these other agents as initial therapy is recommended when a diuretic cannot be used or when a recommended when a diuretic cannot be used or when a compelling indication is present that requires the use of a compelling indication is present that requires the use of a specific drug ...specific drug ...

If the initial drug selected is not tolerated or is If the initial drug selected is not tolerated or is contraindicated, then a drug from one of the other classes contraindicated, then a drug from one of the other classes proven to reduce CV events should be substituted.proven to reduce CV events should be substituted.

JNC 7. Hypertension 2003;42:1206–1252.JNC 7. Hypertension 2003;42:1206–1252.

0.400.40 0.650.65 0.900.90 1.151.15

Diuretics Diuretics Diuretics Diuretics betterbetter worse worse

Meta-analysis of Low-dose Meta-analysis of Low-dose Diuretics versus PlaceboDiuretics versus Placebo

Psaty, et al. JAMA. 2003;289:2534-2544

CHDCHD 0.79 0.79 0.002 0.002

Heart failureHeart failure 0.51 0.51 <0.001 <0.001

StrokeStroke 0.71 0.71 <0.001 <0.001

CVD eventsCVD events 0.76 0.76 <0.001 <0.001

CVD mortalityCVD mortality 0.81 0.81 0.001 0.001

Total mortalityTotal mortality 0.90 0.90 0.002 0.002

OutcomeOutcome RR RR PP

Relative Risk and 95% Confidence IntervalsRelative Risk and 95% Confidence Intervals

Final Outcomes ResultsDoxazosin vs. Chlorthalidone

Favors Doxazosin Favors ChlorthalidoneFavors Doxazosin Favors Chlorthalidone0.500.50 11 22 33

CHD

All-Cause Mortality

Combined CHD

Stroke

Heart Failure

Combined CVD, p< 0.0001 1.20 (1.13 - 1.27)

1.80 (1.61 - 2.02)

1.26 (1.10 - 1.46)

1.07 (0.99 - 1.16)

1.03 (0.94 - 1.13)

1.03 (0.92 - 1.15)

Hypertension 2003;42:239-246Hypertension 2003;42:239-246

ALLHAT

Major Outcomes

Amlodipine/Chlorthalidone

0.50 1 2

ESRD 1.12 (0.89-1.40)

Heart Failure 1.38 (1.25-1.52)

Combined CVD 1.04 (0.99-1.09)

Stroke 0.93 (0.82-1.06)

All-Cause Mortality 0.96 (0.89-1.02)

CHD 0.98 (0.90-1.07)

Favors FavorsAmlodipine Chlorthalidone

Relative Risks and 95% Confidence IntervalsALLHAT

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

Lisinopril/ChlorthalidoneLisinopril/Chlorthalidone

0.500.50 11 22

1.11 (0.88-1.38)1.11 (0.88-1.38)

1.19 (1.07-1.31)1.19 (1.07-1.31)

1.10 (1.05-1.16)1.10 (1.05-1.16)

1.15 (1.02-1.30)1.15 (1.02-1.30)

1.00 (0.94-1.08)1.00 (0.94-1.08)

0.99 (0.91-1.08)0.99 (0.91-1.08)

Favors FavorsLisinopril Chlorthalidone

ESRD

Heart Failure

Combined CVD

Stroke

All-Cause Mortality

CHD

Major OutcomesRelative Risks and 95% Confidence Intervals

ALLHAT

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

Hypertension Treatment by Drug ClassHypertension Treatment by Drug Class

0

10

20

30

40

50

60

1978 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004

Year

% o

f T

reat

ed P

atie

nts

on

Med

icat

ion

Calcium Channel Blockers

Beta Blockers

Diuretics

ACE Inhibitors

ARBs

IMS Health NDTI, 1978-2004IMS Health NDTI, 1978-2004

0

100000

200000

300000

400000

500000

600000

700000

800000

900000

1000000

02Q1 02Q2 02Q3 02Q4 03Q1 03Q2 03Q3 03Q4 04Q1 04Q2 04Q3 04Q4

To

tal

Pre

scri

pti

on

s

Diuretics

ACE Ihhibitors

Calcium Channel Blockers

ARBs

IMS Health NDTI, 1978-2004IMS Health NDTI, 1978-2004

Hypertension Treatment by Drug ClassHypertension Treatment by Drug Class

Drug Utilization by DrugDrug Utilization by Drug

0

1000

2000

3000

4000

5000

6000

7000

8000

02Q1 02Q2 02Q3 02Q4 03Q1 03Q2 03Q3 03Q4 04Q1 04Q2 04Q3 04Q4

To

tal

Pre

scri

pti

on

s

Lisinopril

HCTZ

Amlodipine

IMS Health NDTI, 1978-2004IMS Health NDTI, 1978-2004

0%

5%

10%

15%

20%

25%

2001 2002 2003 2004 2005 2006 2007

Thiazide Diuretic Use for Hypertension, US, 2001-06Proportion of all compound uses, IMS Health NDTI

U.S. Hypertension Guidelines

• JNC 7: Thiazide-type diuretics should be initial drug

therapy for most, either alone or combined with

other drug classes.

• VA-DoD CPGs: Thiazide-type diuretics are preferred

in patients with uncomplicated hypertension; most

compelling indications should include a diuretic.

VA Pharmacy Benefits VA Pharmacy Benefits ManagementManagement

Antihypertensive Medications in VAPercent Patient Utilization

56

37

23

44

18

95 3

115

1720

3841

49

63

0

20

40

60

80

ACEI BB Thiazide CCB Alpha Loop Other ARB

2000

2001

2002

2003

2004

2005

Multi-Drug Therapy in VAMulti-Drug Therapy in VAPercent on ThiazidePercent on Thiazide

54

40

0

10

20

30

40

50

60

2 Meds 3 Meds

2000

2001

2002

2003

2004

2005

VA Pharmacy Benefits VA Pharmacy Benefits ManagementManagement

Antihypertensive Medications in VAPercent Monotherapy

41

20

14 15

52

0.54

0

10

20

30

40

50

ACEI BB Thiazide CCB Alpha Loop Other ARB

2000

2001

2002

2003

2004

2005

Achieving BP Goal With or Without Drug Achieving BP Goal With or Without Drug in 2-Drug Combinations:in 2-Drug Combinations:

VA Single-Drug Therapy StudyVA Single-Drug Therapy Study

Achieving BP Goal With or Without Drug Achieving BP Goal With or Without Drug in 2-Drug Combinations:in 2-Drug Combinations:

VA Single-Drug Therapy StudyVA Single-Drug Therapy Study

69

5856 56

54 5351

58 58 5961 60

40

50

60

70

80

HCTZ CLON DILT ATEN CAPT PRAZ

With Without

% D

BP

<90

mm

Hg

% D

BP

<90

mm

Hg

Materson, et al. J Human Hypertens 1995;9:791-796Materson, et al. J Human Hypertens 1995;9:791-796

VA Thiazide Diuretic Performance Measurement starting in FY 07

Universe: Outpatients with a diagnosis of hypertension AND Actively on antihypertensive therapy

Measure(s): Outpatients with a diagnosis of uncomplicated hypertension on: Antihypertensive mono-drug therapy

which consists of a thiazide diureticAntihypertensive multi-drug therapy

which includes a thiazide diuretic

VA Thiazide Diuretic Measure Uncomplicated Exclusions due to Compelling Indications

Patients with an outpatient diagnosis at any facility within the past twenty-four months prior to the end date of the rolling three month period being evaluated as follows: Diabetes Post AMI Supraventricular Tachycardia Angina

Initial Combinations of Medications*

DiureticsDiuretics

ACE inhibitorsACE inhibitorsoror

ARBsARBs

CalciumCalciumantagonistsantagonists

* Compelling indications may modify this.

Can add: reserpine, aldosterone antagonist or Can add: reserpine, aldosterone antagonist or amiloride, amiloride, -blocker, alternative CCB, vasodilator, -blocker, alternative CCB, vasodilator, -blocker, -blocker, -blocker, and/or central agonist-blocker, and/or central agonist

Hypertension in the U.S. increased in prevalence until 1999: 70 million.

Preventive efforts should be intensified on many fronts, especially lifestyle changes in prehypertensive individuals.

BP control rates have increased in the U.S. since 1999-2000, especially in minorities, but still remains less than the 50% “Healthy People 2010” goal.

Improving the Care of the Improving the Care of the Hypertensive Patient: US Hypertensive Patient: US

PerspectivePerspective Conclusions - 1 Conclusions - 1

BP control rates have increased even more in some practice settings such as the VA: audit and feedback appear central.

Better BP control is associated with increases in dosing and numbers of drugs.

Thiazide diuretic use should continue to increase both for better CV prevention and improved BP control.

We have an excellent armamentarium of lifestyle methods and AHT drugs – further education is needed on how to use them.

Improving the Care of the Improving the Care of the Hypertensive Patient: US Hypertensive Patient: US

PerspectivePerspective Conclusions - 2 Conclusions - 2