Daily Dilemmas in Daily Dilemmas in Hypertension ManagementHypertension Management

ObjectivesObjectives

Review the impact of hypertension on Review the impact of hypertension on societysociety

Review several current questions in Review several current questions in hypertension managementhypertension management

Joint National Committee (JNC7)Joint National Committee (JNC7)

BP Classification SBP DBPBP Classification SBP DBP

Normal <120 and <80Normal <120 and <80

Pre Hypertension 120-139 or 80-89Pre Hypertension 120-139 or 80-89

Stage I Hypertension 140 – 159 or 90 - 99Stage I Hypertension 140 – 159 or 90 - 99

Stage II Hypertension > 160 or > 100Stage II Hypertension > 160 or > 100

7.3

32.6

66.3

0

20

40

60

80

100

Pre

vale

nce

(%

)

18 - 39 40 - 59 > 59

Age

Prevalence of Hypertension in the US 1999-2004

Ong, et al. Hypertension, 2007

Healthy People 2010Healthy People 2010

Reduce prevalence of HTN to 16% (at Reduce prevalence of HTN to 16% (at 28% in 2000)28% in 2000)

Target 50% overall hypertension control Target 50% overall hypertension control raterate

Target 95% intervention rate (including life Target 95% intervention rate (including life style modification)style modification)

68 71 76

58 60 65

0

20

40

60

80

100

Per

cen

t (%

)

Awareness Treatment

Trends in Hypertension Awareness and Treatment

200020022004

Ong, et al. Hypertension, 2007

2933

37

5054

57

24

36 38

0

20

40

60

80

100

Pe

rce

nt

at

Go

al

(%)

Hypertension On Treament Diabetics

Treatment Group

Overall Hypertension Control

200020022004

Ong, et al. Hypertension, 2007

Treatment of HypertensionTreatment of Hypertension

Not at Goal Blood Pressure

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 2-drug combination for most

(usually thiazide-type diuretic and ACEI, or ARB, or BB, or CCB)

Stage 1 Hypertension Thiazide-type diuretics for most.

May consider ACEI, ARB, BB, CCB,

or combination.

Without Compelling Indications

Not at Goal

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

Adapted from JNC7

Treatment OptionsTreatment OptionsDiureticsDiuretics Adrenergic Adrenergic

BlockersBlockersVasodilatorsVasodilators

ThiazidesThiazidesChlorthalidoneChlorthalidone

IndapamideIndapamide

MetolazoneMetolazone

ThiazidesThiazides

LoopsLoopsBumetanideBumetanide

FurosimideFurosimide

ToremideToremide

Aldosterone Aldosterone blockersblockersSpironaldactoneSpironaldactone

EplerenoneEplerenone

Potassium Potassium sparerssparersAmilorideAmiloride

TriamtereneTriamterene

Peripheral Peripheral InhibitorsInhibitorsGuanadrelGuanadrel

GuanethidineGuanethidine

ReserpineReserpine

Central alpha-Central alpha-agonists agonists ClonidineClonidine

GuanzbenzGuanzbenz

GuanfacineGuanfacine

MethyldopaMethyldopa

Alpha-blockersAlpha-blockersDozazosinDozazosin

PrazosinPrazosin

TerazosinTerazosin

Beta-blockersBeta-blockersAcebutolAcebutol

AtenololAtenolol

BetaxololBetaxolol

BisoprololBisoprolol

CarteololCarteolol

MetoprololMetoprolol

NadololNadolol

PenutololPenutolol

PindololPindolol

PropranololPropranolol

TimololTimolol

CombinedCombinedCarvediolCarvediol

LabetololLabetolol

DirectDirectHydralazineHydralazine

MinoxidilMinoxidil

Calcium channel Calcium channel blockerblockerDihydropyridinesDihydropyridines

AmlodipineAmlodipine

FelodipineFelodipine

IsradipineIsradipine

NicardipineNicardipine

NifedipineNifedipine

NisoldipineNisoldipine

DiltiazemDiltiazem

VerapamilVerapamil

Direct renin Direct renin antagonistantagonistAliskirenAliskiren

ACE-IACE-IBenazeprilBenazepril

CaptoprilCaptopril

EnalaprilEnalapril

FosinoprilFosinopril

LisinoprilLisinopril

MoexiprilMoexipril

QuinaprilQuinapril

PerindoprilPerindopril

RamiprilRamipril

TrandolaprilTrandolapril

ARBARBCandesartanCandesartan

EprosartanEprosartan

IrbesartanIrbesartan

LosartanLosartan

TelmisartanTelmisartan

ValsartanValsartan

The Lancet, Volume 362, Issue 9395, 2003

Comparisons of TherapyComparisons of Therapy

Benefits of Lowering Blood Benefits of Lowering Blood PressurePressure

Average Percent Average Percent

ReductionReduction

Stroke incidence Stroke incidence 35–40%35–40%

Myocardial infarctionMyocardial infarction 20-25%20-25%

Heart failureHeart failure 50% 50%

Question #1Question #1

I have a 86 year-old Caucasian female I have a 86 year-old Caucasian female patient with osteoporosis and a history of patient with osteoporosis and a history of breast cancer. Here clinic blood pressure breast cancer. Here clinic blood pressure is always 190/80.is always 190/80.

What should be her target systolic blood What should be her target systolic blood pressure?pressure?

Scope of the ProblemScope of the Problem

18-29 30-39 40-49 50-59 60-69 70-79 80+0

70

80

110

130

150

18-29 30-39 40-49 50-59 60-69 70-79 80+0

70

80

110

130

150

0

70

80

110

130

150

0

70

80

110

130

150D

BP

(mm

Hg

)S

BP

(mm

Hg

)D

BP

(mm

Hg

)S

BP

(mm

Hg

)

DB

P(m

m H

g)

SB

P(m

m H

g)

DB

P(m

m H

g)

SB

P(m

m H

g)

Men, Age (y) Women, Age (y)

Non-Hispanic BlackNon-Hispanic WhiteMexican American

Pulse pressure Pulse pressure

Mean Systolic and Diastolic BP by Age and Race/Ethnicity for Men and Women (US Population ³Age 18 Years, NHANES III)

Burt VI, et al. Burt VI, et al. HypertensionHypertension. 1995;25:305-313. 1995;25:305-313..

Benefits of Lowering Blood Benefits of Lowering Blood PressurePressure

Average Percent Average Percent

ReductionReduction

Stroke incidence Stroke incidence 35–40%35–40%

Myocardial infarctionMyocardial infarction 20-25%20-25%

Heart failureHeart failure 50% 50%

0123456789

10

Cu

mu

lati

ve s

troke r

ate

p

er

10

0 p

ers

on

s

0 12 36 60Months of follow-up

SHEP Cumulative Stroke RateSHEP Cumulative Stroke Rate

24 48 72

P=0.0003

Placebo(n=2,371)

Active Rx (n=2,365)

SHEP=Systolic Hypertension in the Elderly Program

SHEP Research Group. JAMA. 1991;265:3255-3264.Copyright ©1991, American Medical Association. Hypertensiononline.org

36% reduction in stroke rate

0.20

0.40

0.60

0.80

1.00

1.20

1.40

1.60

Rela

tive r

isk (

95%

CI)

Stroke CHD

Active Therapy vs. Placebo

CHF Death

0.630.63

0.460.46

0.680.68

0.870.87

CVD

0.750.75

SHEP Cardiovascular Disease EndpointsSHEP Cardiovascular Disease Endpoints

SHEP Research Group. JAMA. 1991;265:3255-3264.

SHEP=Systolic Hypertension in the Elderly Program

CHD=coronary heart disease; CHF=congestive heart failure; CVD=cardiovascular disease

Hypertensiononline.org

70

80

90

100

Su

rviv

al fr

ee o

f even

t (%

)

Year of follow-up

EWPHE Cardiovascular Mortality EWPHE Cardiovascular Mortality On-Treatment AnalysisOn-Treatment Analysis

Active (n=416)

Placebo (n=424)

P=0.023

0 1 3 62 4 5 7

Amery A, et al. Lancet. 1985;1:1349-1354.Reprinted with permission from Elsevier Science.

EWPHE=European Working Party on High Blood Pressure in the Elderly

Hypertensiononline.org

Blood Pressure & The Very ElderlyBlood Pressure & The Very Elderly

Epidemiologic population studies suggest Epidemiologic population studies suggest better survival with higher levels of blood better survival with higher levels of blood pressurepressure

Worse survival reported in hypertensives Worse survival reported in hypertensives

with SBP levels below 140 mmHgwith SBP levels below 140 mmHg (Oates et al. (Oates et al. 2007)2007)

Meta-analysis (n=1670)Meta-analysis (n=1670) (Gueyffier et al. 1997)(Gueyffier et al. 1997) 36% reduction in the risk of stroke (BENEFIT)36% reduction in the risk of stroke (BENEFIT)14% (p=0.05) increase in total mortality (RISK)14% (p=0.05) increase in total mortality (RISK)

The Trial:International, multi-centre, randomised double-blind placebo controlled

Inclusion Criteria: Exclusion Criteria:Aged 80 or more, Standing SBP < 140mmHgSystolic BP; 160 -199mmHg Stroke in last 6 months+ diastolic BP; <110 mmHg, DementiaInformed consent Need daily nursing care

CHF or Cr more than 1.7Primary Endpoint: All strokes (fatal and non-fatal)

Target blood pressure

150/80 mmHg

All stroke(30% reduction)

PlaceboIndapamideSR ±perindopril

Heart Failure(64% reduction)

Total Mortality(21% reduction)

ConclusionsConclusions

Antihypertensive treatment based on indapamide ± Antihypertensive treatment based on indapamide ± perindopril reduced stroke mortality and total perindopril reduced stroke mortality and total mortality in a very elderly cohort.mortality in a very elderly cohort.

NNT (2 years) = 94 for stroke and 40 for mortalityNNT (2 years) = 94 for stroke and 40 for mortality

Large and significant benefit in reduction of heart Large and significant benefit in reduction of heart failure events and for combined endpoint of failure events and for combined endpoint of cardiovascular eventscardiovascular events

Goal blood pressure was 150/80Goal blood pressure was 150/80

INVEST Trial Secondary analysisINVEST Trial Secondary analysis

The risk for the The risk for the primary endpoint primary endpoint (death, myocardial (death, myocardial infarction, or stroke) infarction, or stroke) progressively progressively increased with low increased with low diastolic blood diastolic blood pressure.pressure.

AIM 144:884 (2006)

ConclusionsConclusions

Evidence supports moderate blood Evidence supports moderate blood pressure reduction in the very elderly to pressure reduction in the very elderly to goal of 150/80goal of 150/80

Excessive reduction of diastolic pressure Excessive reduction of diastolic pressure may have adverse consequences may have adverse consequences

My PatientMy Patient

Target blood pressure of 150/80Target blood pressure of 150/80Achieve goal with low dose thiazide diurecticAchieve goal with low dose thiazide diurectic

Consider ACE-I or CCB for combination Consider ACE-I or CCB for combination therapytherapy

Monitor home blood pressuresMonitor home blood pressuresConsider titrating to standing blood pressureConsider titrating to standing blood pressure

Question #2Question #2

Is combination therapy with an Is combination therapy with an angiotensin-converting enzyme inhibitor angiotensin-converting enzyme inhibitor (ACE) and an angiotensin receptor blocker (ACE) and an angiotensin receptor blocker (ARB) appropriate for my patient with (ARB) appropriate for my patient with essential hypertension requiring an essential hypertension requiring an additional agent to reach goal?additional agent to reach goal?

Renin-Angiotensin PathwayRenin-Angiotensin Pathway

www.kidney.org

Practice TrendsPractice Trends

Since 2000, several trials compared dual Since 2000, several trials compared dual ACE-ARB therapy in nephropathy and ACE-ARB therapy in nephropathy and coronary disease coronary disease COOPERATE, CHARM, VALLIANT, COOPERATE, CHARM, VALLIANT,

ONTAGERT ONTAGERT

General thought: More blockade must be General thought: More blockade must be betterbetter

COOPERATECOOPERATE

Evaluated combination of losartan and Evaluated combination of losartan and trandolapril in non-diabetic proteinuric trandolapril in non-diabetic proteinuric renal diseaserenal disease

Significant benefit from combination Significant benefit from combination therapy in slowing progression of diseasetherapy in slowing progression of disease

Publication retracted by the Lancet in Publication retracted by the Lancet in October 2009October 2009

Lancet 2003 Jan 11;361(9352):117-24 Lancet 2009 Oct 9;374(9697):1226

ACE and ARB medications equally reduce ACE and ARB medications equally reduce proteinuriaproteinuria

Combination therapy has greater effectCombination therapy has greater effect

Unable to assess outcomesUnable to assess outcomes

Ann Intern Med. 2008 Jan 1;148(1):30-48

Effects of telmisartan, ramipril, or both on Effects of telmisartan, ramipril, or both on death from cardiovascular causes, MI, death from cardiovascular causes, MI, stroke, or hospitalization for heart failurestroke, or hospitalization for heart failure

No No significant difference in primary significant difference in primary outcomes between any armsoutcomes between any arms

ONTARGETONTARGET

NEJM 2008; 358:1547-1559NEJM 2008; 358:1547-1559

ONTARGET Dual TherapyONTARGET Dual Therapy

Average BP reduction of 2-3 mmHg in Average BP reduction of 2-3 mmHg in combination armcombination armExpected 4-5% reduction in primary outcome Expected 4-5% reduction in primary outcome

not foundnot foundSignificant increases in:Significant increases in:

HypotensionHypotensionHyperkalemiaHyperkalemiaRenal dysfunctionRenal dysfunctionSyncope Syncope

NEJM 2008; 358: 1547-1559NEJM 2008; 358: 1547-1559

ONTARGET ConclusionsONTARGET Conclusions

Patients who have vascular disease or Patients who have vascular disease or high risk diabetes, telmisartan is not high risk diabetes, telmisartan is not inferior to ramiprilinferior to ramipril

No additional benefit from combination No additional benefit from combination therapytherapySignificantly more riskSignificantly more riskBP reduction not beneficialBP reduction not beneficial

NEJM 2008; 358: 1547-1559NEJM 2008; 358: 1547-1559

My PatientMy Patient

ACE or ARB is appropriateACE or ARB is appropriate

Combination therapy not routinely Combination therapy not routinely indicated for blood pressure reductionindicated for blood pressure reductionSpecific populations may have benefit from Specific populations may have benefit from

combination therapy combination therapy Consider other options for proteinuria Consider other options for proteinuria

reduction if indicatedreduction if indicated

Question #3Question #3

I have a 50 year-old male patient with I have a 50 year-old male patient with elevated systolic blood pressures over 160 elevated systolic blood pressures over 160 mmHg at every clinic visit. His home mmHg at every clinic visit. His home blood pressure is always less than 130 blood pressure is always less than 130 mmHg.mmHg.

What is his cardiovascular risk from his What is his cardiovascular risk from his elevated clinic readings?elevated clinic readings?

Blood Pressure Response to Physician or Nurse

0

5

10

15

20

25

Peak 5 Minutes 10 Minutes

Time

Sy

sto

lic

Ch

an

ge

fro

m B

as

eli

ne

(m

mH

g)

Physician

Nurse

Hypertension 1987;9:209

White Coat HypertensionWhite Coat Hypertension

Definition:Definition:DaytimeDaytime blood pressure average less than blood pressure average less than

130/80 mmHg130/80 mmHgClinic readings greater than 140/90 mmHgClinic readings greater than 140/90 mmHg

White Coat EffectWhite Coat EffectElevated pressure in the clinic superimposed Elevated pressure in the clinic superimposed

on essential hypertensionon essential hypertension

Scope of the ProblemScope of the Problem

Prevalence range 10 – 30% of patients Prevalence range 10 – 30% of patients with clinical hypertensionwith clinical hypertensionDiagnosis of hypertension usually made on Diagnosis of hypertension usually made on

clinic blood pressure recordingsclinic blood pressure recordings10% - 74% will progress to hypertension over 10% - 74% will progress to hypertension over

5 years5 years

Historically considered a benign conditionHistorically considered a benign condition

Outcomes in White Coat Outcomes in White Coat Hypertension (WCH)Hypertension (WCH)

3.2 3.7

0.8

3.7

7.9

15.3

02468

101214161820

% o

f P

atie

nts

Non CardiacDeath

CVA CoronaryEvent

WCH

SustainedHTN

P<0.001

P<0.001

NS

Khatter et al, Circulation. 1998;98:1892

Hypertension. 2005;45:203-208

Analysis of data from 4 cohort studies in 3 Analysis of data from 4 cohort studies in 3 countriescountries

Followed for a median 5.3 yearsFollowed for a median 5.3 years

Evaluated incidence of strokeEvaluated incidence of stroke

ResultsResults

Significant increased risk of stroke from:Significant increased risk of stroke from:Elevated office and sleep systolic pressureElevated office and sleep systolic pressureTobacco useTobacco useOlder ageOlder ageDiabetesDiabetes

No clear significant increased risk from No clear significant increased risk from white coat hypertensionwhite coat hypertension

Six-Year Risk-Factor Adjusted Six-Year Risk-Factor Adjusted Probability of StrokeProbability of Stroke

Hypertension. 2005;45:203-208

0

2

4

6

8

Pro

bab

ilit

y

Women Men Women Men

Normotensive

WCH

HTN

Non-Smokers Smokers

Cumulative Hazard for StrokeCumulative Hazard for Stroke

Hypertension. 2005;45:203-208

ConclusionsConclusions

Patients with white coat hypertension are Patients with white coat hypertension are at risk for progression to hypertension, at risk for progression to hypertension, likely greater than a normotensive cohortlikely greater than a normotensive cohort

While the cardiovascular risk from WCH is While the cardiovascular risk from WCH is less than with hypertension, it may still less than with hypertension, it may still carry some riskcarry some risk

My PatientMy Patient

Cardiac risk stratification from other risk Cardiac risk stratification from other risk factorsfactorsLifestyle modificationLifestyle modification

Low sodium dietLow sodium dietRegular exerciseRegular exercise

Occasional home blood pressure monitoringOccasional home blood pressure monitoringConsider 24 hour ambulatory blood pressure Consider 24 hour ambulatory blood pressure

monitormonitor

ConclusionsConclusions

To meet blood pressure goals we must:To meet blood pressure goals we must:Make the diagnosis more frequentlyMake the diagnosis more frequentlyEducate our patientsEducate our patientsTreat more aggressively, with simple Treat more aggressively, with simple

medication regimensmedication regimensReassess to reach goalsReassess to reach goals

Thank youThank you

ResourcesResources

Amery A, et al. Amery A, et al. LancetLancet. 1985;1:1349-1354.. 1985;1:1349-1354.

Ann Med 2006; 144:884Ann Med 2006; 144:884

Burt VI, et al. Burt VI, et al. HypertensionHypertension. 1995;25:305-313.. 1995;25:305-313.

Hypertension.Hypertension. 1987;9:209 1987;9:209

HypertensionHypertension. 2005;45:203-208. 2005;45:203-208

Khatter et al; Khatter et al; CirculationCirculation. 1998;98:1892. 1998;98:1892

LancetLancet 2003;361(9352):117-24 2003;361(9352):117-24

LancetLancet 2003; 362 (9395): 2003; 362 (9395):

Ong, et al. Ong, et al. Hypertension.Hypertension. 2007 2007

SHEP Research Group. SHEP Research Group. JAMAJAMA. 1991;265:3255-3264.. 1991;265:3255-3264.