Managing ISOLATED Managing ISOLATED SYSTOLIC HYPERTENION in SYSTOLIC HYPERTENION in

the Elderlythe Elderly

Ass. Prof. Roland KASSABAss. Prof. Roland KASSABHead of Division of CardiologyHead of Division of CardiologyHotel-Dieu de France, BeirutHotel-Dieu de France, Beirut

12 April 200312 April 2003

ISHISH

DefinitionDefinition

PrevalencePrevalence

PathophysiologyPathophysiology

Risk StatificationRisk Statification

Outcomes StudiesOutcomes Studies

TherapyTherapy

DEFINITIONDEFINITION

According to JNC-VI and WHO/ISH:According to JNC-VI and WHO/ISH:

SBP SBP ≥ 140 mmHg, DBP < 90 mmHg≥ 140 mmHg, DBP < 90 mmHg

Grade 1Grade 1: SBP < 160 mmHg : SBP < 160 mmHg

Subgr. borderline SBP < 150 mmHgSubgr. borderline SBP < 150 mmHg

Grade 2Grade 2: SBP < 180 mmHg: SBP < 180 mmHg

Grade 3Grade 3: SBP ≥ 180 mmHg: SBP ≥ 180 mmHg

JNC VI Guidelines for Definition JNC VI Guidelines for Definition and Dg of HTAand Dg of HTA

Defined as Defined as SBP SBP ≥ 140≥ 140, , DBP ≥ 90mmHgDBP ≥ 90mmHg,, or taking any antihypertensive medication.or taking any antihypertensive medication.■ ■ When SBP and DBP fall into different categories, When SBP and DBP fall into different categories,

the the HigherHigher one is used to classify the BP. one is used to classify the BP.■ ■ Measurements are based on the average of Measurements are based on the average of 2 or2 or

more BP readingsmore BP readings at each of at each of 2 or more visits2 or more visits after the initial screening.after the initial screening.

■■ Measurements must be taken with equipment Measurements must be taken with equipment that meets that meets certification criteriacertification criteria, and in a , and in a standardized fashionstandardized fashion. .

Definition of HTA (JNC VI)Definition of HTA (JNC VI)

Hypertension is defined as consistent readings Hypertension is defined as consistent readings 140/90140/90 mm Hgmm Hg in in youngyoung and and olderolder adults adults

Classification of BP for adults age 18 and olderClassification of BP for adults age 18 and older

CategoryCategory Systolic(mmHgSystolic(mmHg Diastolic(mmHg)Diastolic(mmHg)

OptimalOptimal <120<120 andand <80<80

NormalNormal <130<130 andand <85<85

High-normalHigh-normal 130-139130-139 oror 85-8985-89

HypertensionHypertension

Stage Stage 11 140-159140-159 oror 90-9990-99

Stage Stage 22 160-179160-179 oror 100-109100-109

Stage Stage 33 180180 oror 110110

The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. November 1997. NIH publication 98-4080

PREVALENCEPREVALENCE

Latest Definition: Latest Definition: ≥140/<90 : ≥140/<90 : little datalittle data

Prevalence of ISH Prevalence of ISH with agewith age

Most common type of Most common type of HTA in the elderlyHTA in the elderly

Most preval. type of Most preval. type of untreated HTA ≥ 60 yuntreated HTA ≥ 60 y..

Age Age

( % )( % )

5050

6060

7070

80+80+

0,80,8

5,05,0

8-12,68-12,6

23 - 2523 - 25

Old Definition: ≥ 160 / < 90

Hypertension in the ElderlyHypertension in the Elderly(>60 Years) in Spain(>60 Years) in Spain

Prevalence of arterial Prevalence of arterial hypertension: hypertension: 68.3%68.3%

Prevalence of ISH in untreated Prevalence of ISH in untreated hypertensives: hypertensives: 71.6%71.6%

Banegas J et al. J Hypertens (submitted)

<40<40 40-49 40-49 50-59 50-59 60-69 60-69 70-79 80+ 70-79 80+Age (y)Age (y)

100100

%%

80%80%

60%60%

40%40%

20%20%

0%0%

Franklin et al, Hypertension 2001Franklin et al, Hypertension 2001

4%4% 10% 10% 18% 18% 28% 28% 27% 13% 27% 13%

NHANES IIINHANES IIIF

req

uen

cy o

f tr

eatm

ent

Fre

qu

ency

of

trea

tmen

t

Fai

lure

s b

y H

TN

su

bty

pe

(%)

Fai

lure

s b

y H

TN

su

bty

pe

(%)

ISHISH S/DH S/DH IDHIDH

Framingham: Prevalence of Isolated Framingham: Prevalence of Isolated Systolic Hypertension in the Elderly*Systolic Hypertension in the Elderly*

12.3%

30.3%57.4%

7.2%

27.7%

65.1%

Wilking SV et al. JAMA.1988;260:3451-3455.

Isolated Diastolic Hypertension

Isolated SystolicHypertension

Combined Hypertension

*Age range: 65-89 years

MenMen WomenWomen

PATHOPHYSIOLOGYPATHOPHYSIOLOGY

B.P. = Cardiac Output X Periph. ResistanceB.P. = Cardiac Output X Periph. Resistance ( Qc ) ( R )( Qc ) ( R )

↑ ↑ B.P. ↔ ↑ QcB.P. ↔ ↑ Qc oror

↑ ↑ RR

Characteristics of Hypertension Characteristics of Hypertension in the Elderlyin the Elderly

Increased arterial stiffnessIncreased arterial stiffness

Altered Altered renal functionrenal function

Frequent Frequent diabetesdiabetes and and hyperlipidemia hyperlipidemia

Frequent association with Frequent association with CV diseaseCV disease and and heart failureheart failure

Frequent occurrence with Frequent occurrence with other complicationsother complications and disease states (polypharmacy, and disease states (polypharmacy, noncompliance are common issues) noncompliance are common issues)

The Effects of Age on Blood The Effects of Age on Blood PressurePressure

Systolic BP rises continuously with ageSystolic BP rises continuously with age

Diastolic BPDiastolic BP rises continuously until age rises continuously until age 60-70 years60-70 years– It It fallsfalls thereafter as a consequence of thereafter as a consequence of

increased arterial stiffnessincreased arterial stiffness

Pulse pressure increasesPulse pressure increases continuously continuously with agewith age

PATHOPHYSIOLOGYPATHOPHYSIOLOGY

Stiffened aorta

Increased pulse-wave velocity

More stroke volume returned to aorta in systolerather than diastole

SBP augmented further, DBP reduced

Potential harm of reducing DBP (J curve)

Smulyan H, Safar ME. Ann Intern Med. 2000;132:233-237.

RISK STRATIFICATIONRISK STRATIFICATION

Components of Risk Stratification: JNC VI:Components of Risk Stratification: JNC VI:

MAJOR RISK FACTORSMAJOR RISK FACTORS

♥ ♥ SmokingSmoking

♥ ♥ DyslipidemiaDyslipidemia

♥ ♥ Diabetes MellitusDiabetes Mellitus

♥ ♥ Age ≥ 60 y.Age ≥ 60 y.

♥ ♥ Sex ( ♂, post-menopausal ♀ )Sex ( ♂, post-menopausal ♀ )

♥ ♥ Family history or Co-vx disease:♀< 65y, ♂< 55yFamily history or Co-vx disease:♀< 65y, ♂< 55y

RISK STRATIFICATIONRISK STRATIFICATION

TARGET ORGAN DAMAGE ( TOD )TARGET ORGAN DAMAGE ( TOD )

♥ ♥ Heart Disease: LVH, Angina or previousHeart Disease: LVH, Angina or previous

MI, prior CABG, HFMI, prior CABG, HF

♥ ♥ Stroke or TIAStroke or TIA

♥ ♥ NephropathyNephropathy

♥ ♥ PADPAD

♥ ♥ Retinopathy.Retinopathy.

Risk Stratification and TreatmentRisk Stratification and Treatment

StageStage Group AGroup A Group BGroup B Group CGroup C

No risk No risk factors; no factors; no TOD/CCDTOD/CCD

At least 1ris At least 1ris f, no DM or f, no DM or

TOD, CCDTOD, CCD

TOD/CCD TOD/CCD and/or DM, and/or DM, ±other risk f±other risk f

High-Norm.High-Norm. LMLM LMLM DrugDrug

Stage 1Stage 1 LM (up to 1 LM (up to 1 year)year)

LM ( up to LM ( up to 6 m.)6 m.)

DrugDrug

Stage 2Stage 2 DrugDrug DrugDrug DrugDrug

Systolic vs Diastolic Blood Pressure as Systolic vs Diastolic Blood Pressure as Predictors of Cardiovascular OutcomesPredictors of Cardiovascular Outcomes

Systolic blood pressure (Systolic blood pressure (SBPSBP) is a ) is a stronger predictorstronger predictor of of future cardiovascular events than diastolic blood pressure future cardiovascular events than diastolic blood pressure (DBP)(DBP)11

Patients with a combination of hypertension and Patients with a combination of hypertension and diabetesdiabetes and/or and/or older patientsolder patients benefit most from well-controlled benefit most from well-controlled systolic blood pressuresystolic blood pressure22

In addition, In addition, pulse pressure (PP = SBP minus DBP)pulse pressure (PP = SBP minus DBP) is is increasingly seen as an increasingly seen as an independent predictor of riskindependent predictor of risk for for coronary artery diseasecoronary artery disease33

1. Neaton JD, Wentworth D. Arch Intern Med. 1992;152:56-64. 2. Lee ML et al. Ann Epidemiol. 1999;9:101-107. 3. Franklin SS et al. Circulation.1999;100:354-360.

Adapted from Neaton JD, Wentworth D. Adapted from Neaton JD, Wentworth D. Arch Intern MedArch Intern Med. 1992;152:56-64. . 1992;152:56-64. 

Effect of Systolic Blood Pressure and Effect of Systolic Blood Pressure and Diastolic Blood Pressure on Coronary Heart Diastolic Blood Pressure on Coronary Heart

Disease Mortality: MRFITDisease Mortality: MRFIT

<120<120120-139120-139

140-159140-159160+160+

Systolic BP

Systolic BP

(mm Hg)

(mm Hg)

Diastolic BP

Diastolic BP(mm Hg)

(mm Hg)

CAD Death Rate per

CAD Death Rate per

10,000 Person-Years

10,000 Person-Years

100+100+

80-8980-89

70-7470-74<70<70

75-7975-79

90-9990-99

48.348.3

37.437.434.734.7 43.843.8

38.138.1

80.680.631.031.0

25.525.524.624.6

25.325.325.225.2

24.924.9

23.823.8

16.916.913.913.9

12.812.812.612.6

11.811.8

20.620.6

10.310.311.811.8

8.88.88.58.5

9.29.2

3.03.0

2.52.5

2.02.0

1.51.5

1.01.0

0.50.53030 4040 5050 6060 7070 8080 9090 100100 110110

SBP 170 mm HgSBP 170 mm Hg((P P = 0.0487)= 0.0487)

SBP 150 mm HgSBP 150 mm Hg((P P = 0.0194)= 0.0194)

SBP 130 mm HgSBP 130 mm Hg((P P = 0.0086)= 0.0086)

SBP 110 mm HgSBP 110 mm Hg((P P = 0.2076)= 0.2076)

Coronary Coronary Artery Artery

DiseaseDisease HazardHazard RatioRatio

Pulse Pressure (mm Hg)Pulse Pressure (mm Hg)

Franklin SS et al. Circulation. 1999;100:354-360.

*Pulse pressure = systolic blood pressure (SBP) minus diastolic blood pressure (DBP).*Pulse pressure = systolic blood pressure (SBP) minus diastolic blood pressure (DBP).

N = 1,924N = 1,924

Framingham Study: At Any Level of Systolic BP, Framingham Study: At Any Level of Systolic BP, Pulse Pressure* is a Strong Predictor of Pulse Pressure* is a Strong Predictor of

Cardiovascular EventsCardiovascular Events

OUTCOMES STUDIESOUTCOMES STUDIES

Major Studies of Pharmacologic Tt in Major Studies of Pharmacologic Tt in

ISHISH ►► ►► SHEPSHEP

►► ►► Syst-EURSyst-EUR

►► ►► Syst-ChinaSyst-China

►► ►► ARBs studies: ARBs studies: LIFELIFE sub-study sub-study

ChlorthalidoneChlorthalidone

12.5 mg (C12.5 mg (C11))

ChlorthalidoneChlorthalidone

25 mg (C25 mg (C22))

Atenolol 25 mgAtenolol 25 mg

C 25 mgC 25 mg

Atenolol 50 mgAtenolol 50 mg

C 25 mgC 25 mg

The Systolic Hypertension in the Elderly The Systolic Hypertension in the Elderly Program (SHEP) Trial DesignProgram (SHEP) Trial Design

SHEP Cooperative Research Group. J Clin Epidemiol. 1988;41:1197-1208. SHEP Cooperative Research Group. JAMA. 1991;265:3255-3264.

IC

RandomizationRandomization

- 4 0 8 16Week

- 2 24

PlaceboPlacebo

Placebo CPlacebo C22

Placebo CPlacebo C11

++

__

CC 25 mg25 mg++

__

++

__

++

__++

__++

__

Indicates those with BP not reduced to or below goal ++

__

Indicates those with BP reduced to or below goal

Placebo APlacebo A11

Placebo CPlacebo C22

Placebo APlacebo A22

Placebo CPlacebo C22

Placebo APlacebo A11

Placebo CPlacebo C22

Atenolol 25 mgAtenolol 25 mg

C 25 mgC 25 mg

BV1

IC = initial contact; BV1 = baseline visit 1.

Placebo CPlacebo C22

The Systolic Hypertension in Europe The Systolic Hypertension in Europe (Syst-Eur) Trial Design(Syst-Eur) Trial Design

Amery A et al. Aging. 1991;3:287-302.Staessen JA et al. Lancet. 1997;350:757-764.

Entry criteria

• Age: >60 years

• Sitting SBP 160 mm Hg Sitting DBP <95 mm Hg

• Standing SBP: 140 mm Hg

• Informed consent

Outcome Events

• Death

• Stroke

• Retinal changes

• Myocardial infarction

• Heart failure

• Dissecting aneurysm

• Serum creatinine 4mg %

Placebo

Placebo

Active Treatment

Nitrendipine 10-40 mg Enalapril 5-20 mg Hydrochlorothiazide 12.5-25 mg

Single blindSingle blind

• Visit monthly

• Duration: 3-4 months

Double BlindDouble Blind

• Visit every 3 months

• Duration: 5 years

N = 4,695N = 4,695

Landmark Trials in Isolated Landmark Trials in Isolated Systolic HypertensionSystolic Hypertension

CAD = coronary artery disease; CHF = congestive heart failure; CVD = cardiovascular disease.CAD = coronary artery disease; CHF = congestive heart failure; CVD = cardiovascular disease.

SHEP Cooperative Research Group. SHEP Cooperative Research Group. JAMA.JAMA. 1991;265:3255-3264. 1991;265:3255-3264.Staessen JA et al. Staessen JA et al. Lancet.Lancet. 1997;350:757-764. 1997;350:757-764.

Relative Risk Reduction (%)Relative Risk Reduction (%)

DiureticDiuretic ± ±beta-blockerbeta-blocker

Long-actingLong-actingDHP CCBDHP CCB(nitrendipine)(nitrendipine)

Syst-EurSyst-Eur

SHEPSHEP 4,7364,736 6060 171/77171/77 -36-36 -27-27 -55-55 -32-32

-31-31-29-29-26-26-42-42174/86174/8660604,6954,695

Agent NN AgeAgeEntryEntry

BPBP StrokeStroke CADCAD CHFCHFAllAll

CVDCVD

SHEP Cooperative Research Group. SHEP Cooperative Research Group. JAMA.JAMA. 1991;265:3255-3264. 1991;265:3255-3264. Staessen JA et al. Staessen JA et al. Lancet.Lancet. 1997;350:757-764. 1997;350:757-764.

Isolated Systolic Hypertension Isolated Systolic Hypertension and Stroke Risk Reductionand Stroke Risk Reduction

Cumulative Cumulative Stroke Stroke Rate Rate

per 100 per 100 ParticipantsParticipants

Placebo Placebo

36%36% Reduction at 5 Years Reduction at 5 Years ((P P <0.0003<0.0003))

Follow-up (months)Follow-up (months)

00 1212 2424 3636 4848

66

00

44

22

88

1010

6060

Diuretic Diuretic beta-blocker beta-blocker

42%42% Reduction in Events Reduction in Events ((P P = 0.003)= 0.003)

Follow-up (months)Follow-up (months)

00 1212 2424 3636 4848

66

00

11

33

55

44

22

NitrendipineNitrendipine

Placebo Placebo

Cumulative Rate of Fatal and Nonfatal Stroke Cumulative Rate of Fatal and Nonfatal Stroke

SHEP Syst-EurSHEP Syst-Eur

*Other antihypertensives excluding ACE-Is, ARBs, beta-blockers; T = titration; R = randomization.

LIFE: ISH Study Design and LIFE: ISH Study Design and DosingDosing

Day 14 Day 1 Month 2 Month 4 Month 6

Titration to target blood pressure: <140/<90 mm Hg

Losartan 50 mgLosartan 50 mgoror

Atenolol 50 mgAtenolol 50 mg

PlaceboPlacebo

Losartan 100 mgLosartan 100 mgoror

Atenolol 100 mgAtenolol 100 mg

Hydrochlorothiazide 12.5 mgHydrochlorothiazide 12.5 mg

Other Antihyper-Other Antihyper-tensive Medications*tensive Medications*

HCTZ 12.5 to 25 mgHCTZ 12.5 to 25 mg

TT TT TT

Kjeldsen SE et al. JAMA. 2002;288:1491-1498.

RR

N = 1326

LIFE Isolated Systolic Hypertension LIFE Isolated Systolic Hypertension Substudy: Combination or Monotherapy at Substudy: Combination or Monotherapy at

End of TitrationEnd of Titration

HCTZ = hydrochlorothiazide; D/C = discontinued.

Adapted from Kjeldsen SE et al. JAMA. 2002;288:1491-1498.

12.1%

3.6%

58.8%

25.5%

10.1%

2.6%

55.1%

32.3%

0

15

30

45

60

50 or 100 mg50 or 100 mgmonotherapymonotherapy

50 or 100 mg 50 or 100 mg + HCTZ + HCTZ add-on add-on

100 mg+ add-on

Losartan Losartan (n = 660)(n = 660) Atenolol Atenolol (n = 666)(n = 666)

D/C therapyD/C therapy

Percent

LIFE: Primary Composite End Point in LIFE: Primary Composite End Point in Patients With Isolated Systolic HypertensionPatients With Isolated Systolic Hypertension

Kjeldsen SE et al. JAMA. 2002;288:1491-1498.

Blood pressure reduction was virtually identical in losartan (28/9 mm Hg) and atenolol (28/9 mm Hg) arms.

Patients WithFirst Event

(%)

0

2

4

6

8

10

12

14

16

Study Month

0 6 12 18 24 30 36 42 48 54 60 66

18

LosartanLosartanAtenololAtenolol

Primary Composite End Point

0

2

4

6

8

10

12

14

16

Study Month

0 6 12 18 24 30 36 42 48 54 60 66

18

Total MortalityTotal Mortality

Relative Risk = 0.75Relative Risk = 0.75(95% Cl, 0.56-1.01 (95% Cl, 0.56-1.01 P P = 0.06= 0.06

Relative Risk = 0.72Relative Risk = 0.72(95% Cl, 0.53-1.00) (95% Cl, 0.53-1.00) P P = 0.046= 0.046

LIFE: Components of the Composite Primary LIFE: Components of the Composite Primary End Point in Patients With Isolated Systolic End Point in Patients With Isolated Systolic

HypertensionHypertension

AtenololAtenololLosartanLosartan

Kjeldsen SE et al. JAMA. 2002;288:1491-1498.

0 12 24 4836 60

Myocardial Infarction

Relative Risk = 0.89(95% Cl, 0.55-1.44) P = 0.64

Study MonthStudy Month

0

4

2

8

6

10

0 12 24 4836 60

Stroke

Relative Risk = 0.60(95% Cl, 0.38-0.92) P = 0.02

Study MonthStudy Month

0

4

2

8

6

10

PatientsPatients(%)(%)

PatientsPatients (%)(%)

Study Month

0 12 24 4836 600

4

2

8

6

10

Cardiovascular Mortality

Relative Risk = 0.54(95% Cl, 0.34-0.87) P = 0.01

Study MonthStudy Month

PatientsPatients(%)(%)

LIFE Isolated Systolic Hypertension LIFE Isolated Systolic Hypertension Substudy: ConclusionsSubstudy: Conclusions

Most patients with ISH received Most patients with ISH received combination treatment withcombination treatment with hydrochlorothiazidehydrochlorothiazide (58.8% in the losartan group and 55.1% in the atenolol (58.8% in the losartan group and 55.1% in the atenolol group) group)

>70%>70% of patients that finished the trial received combination therapy of patients that finished the trial received combination therapy

Reductions of 28 mm Hg in systolic blood pressure and 9 mm Hg in diastolic Reductions of 28 mm Hg in systolic blood pressure and 9 mm Hg in diastolic blood pressure were achieved in the losartan and the atenolol groupsblood pressure were achieved in the losartan and the atenolol groups

At the same levels of blood pressure control, losartan significantly At the same levels of blood pressure control, losartan significantly reduced reduced stroke risk and overall cardiovascular mortalitystroke risk and overall cardiovascular mortality but not the risk of suffering a but not the risk of suffering a myocardial infarction myocardial infarction

The impact of The impact of ARB + HCTZARB + HCTZ treatment on cardiac morbidity and mortality treatment on cardiac morbidity and mortality alone needs to be further evaluated in future trialsalone needs to be further evaluated in future trials

Kjeldsen SE et al. JAMA. 2002;288:1491-1498.

Reduction of BP in PatientsReduction of BP in Patients65 Years With Valsartan65 Years With Valsartan

-8.8

-1.2

-19.2*

-5.2*

-25

-20

-15

-10

-5

0SBP DBP

Placebo

Valsartan

*P <0.001, valsartan vs placebo.Neutel JM et al. Clin Ther. 2000;22:961-969.

Change from Baseline(mm Hg)

THERAPYTHERAPY

As with any therapy, the pragmatic As with any therapy, the pragmatic 4 W4 W questions must be answered:questions must be answered:

WWHY ?HY ?

WWHEN ?HEN ?

WWHO ?HO ?

WWHAT ?HAT ?

WHY ?WHY ?

According to the previous trials, in ISH:According to the previous trials, in ISH: ►► Treatment Treatment >> Placebo>> Placebo ► ► Significant Significant ↓ Cardio-vx Morbidity↓ Cardio-vx Morbidity and Mortalityand Mortality

■■ Benefits of Benefits of ↓ Systolic B.P.↓ Systolic B.P. and and PulsePulse PressurePressure

Tx = treatment; C = control (untreated); CAD = coronary artery disease; CV = cardiovascular. Tx = treatment; C = control (untreated); CAD = coronary artery disease; CV = cardiovascular.

Staessen JA et al. Staessen JA et al. LancetLancet. 2000;355:865-872.. 2000;355:865-872.

Meta-Analysis: Reduction of CV Events in Meta-Analysis: Reduction of CV Events in Treated vs Untreated Patients With Isolated Systolic Treated vs Untreated Patients With Isolated Systolic

HypertensionHypertension

0

200

400

600

800

1000

Individuals Individuals AffectedAffected

(N)(N)279279

100100

387387

136136

293293

193193

373373

244244

647647

329329

835835

392392

656656734734

327327 342342

Tx C Tx C Tx C Tx C Tx C

Nonfatal EventsNonfatal Events

DeathsDeaths

StrokeStroke CADCAD All CVAll CVEventsEvents

TotalTotalMortalityMortality

Non-CVNon-CV Mortality Mortality

N = 15,693N = 15,693

30% P <0.0001

26%P <0.0001

Reduction in Odds (%)

23%P <0.001

13% P <0.02

WHEN ?WHEN ?

Appropriate DiagnosisAppropriate Diagnosis of ISH of ISH

Institute Institute Lifestyle ModificationsLifestyle Modifications::

♥♥ Weight lossWeight loss

♥♥ Salt restrictionSalt restriction

♥♥ Exercise programExercise program

♥♥ Reduction of alcohol intakeReduction of alcohol intake

■■ If HT persists, institute If HT persists, institute Drug TreatmentDrug Treatment..

WHO ?WHO ?

All patients with ISHAll patients with ISH

Risks higher in Risks higher in smokerssmokers and and diabeticdiabetic pts pts

Tight Tight control of diabetes, cessation of control of diabetes, cessation of smoking +++smoking +++

In the previous trials, In the previous trials, ↓ in absolute risk ↓ in absolute risk from all major Co-vx events almost from all major Co-vx events almost twice twice in diabetic sub-group.in diabetic sub-group.

WHAT ?WHAT ?

Start with a Start with a Single AgentSingle Agent::

► ► DoseDose should be should be ↓↓ in elderly: ≈ ½ dose in elderly: ≈ ½ dose

► ► Long-actingLong-acting formulations preferred for formulations preferred for

better compliancebetter compliance

► ► Low-doseLow-dose combinations helpful: ↓ S.E. combinations helpful: ↓ S.E.

► ► Titrate ↑Titrate ↑ and/or and/or add 2add 2ndnd agent agent if goal not if goal not

reached reached after 1 to 2 monthsafter 1 to 2 months..

PHARMACOTHERAPYPHARMACOTHERAPY

Avoid agents Avoid agents ↔ profound ↓ in ↔ profound ↓ in Diastolic BP ( Pulse Pressure ++)Diastolic BP ( Pulse Pressure ++)

Avoid agents causing serious Side Avoid agents causing serious Side EffectsEffects

Theoretic advantage of Theoretic advantage of vaso-dilators vaso-dilators improving arterial complianceimproving arterial compliance

Recommendations of JNC VI :Recommendations of JNC VI :

DIURETICSDIURETICS

First-lineFirst-line Tt of ISH in elderly ( SHEP ) Tt of ISH in elderly ( SHEP )

Good control often seen at Good control often seen at low doseslow doses

ThiazidesThiazides: Diuretics of choice: Diuretics of choice

Thiazide diuretics seem to be Thiazide diuretics seem to be > to Beta-> to Beta-

blockers in pts with ISH.blockers in pts with ISH.

CA CHANNEL BLOCKERSCA CHANNEL BLOCKERS

Improve Improve arterial compliancearterial compliance

Well tolerated in Well tolerated in comorbid conditionscomorbid conditions

Low-dose, slow-release agentsLow-dose, slow-release agents

First-line TtFirst-line Tt in Syst-EUR and Syst-China in Syst-EUR and Syst-China

Significant Significant ↓↓ in key end points in key end points

Benefit over Diuretics: ↓ rate of dementia Benefit over Diuretics: ↓ rate of dementia

(by 50%) in treated pts.(by 50%) in treated pts.

BETA BLOCKERSBETA BLOCKERS

First-line Tt in combination with ThiazidesFirst-line Tt in combination with Thiazides

Starting agents Starting agents alonealone in some conditions: in some conditions:

♥ ♥ TachycardiaTachycardia

♥ ♥ CADCAD

♥ ♥ Prior MIPrior MI

N.B. BB with intrinsec N.B. BB with intrinsec ΣΣ activity or combined activity or combined

αα blocker activity may be more effective blocker activity may be more effective

ACEI and ARBsACEI and ARBs

► ► Numerous advantages:Numerous advantages: ♥ ↓ ♥ ↓ ProteinuriaProteinuria ♥ ♥ Slow renal diseaseSlow renal disease ♥ ♥ Improve systolic dysfunctionImprove systolic dysfunction ♥ ↓ ♥ ↓ SBP in pts with ISHSBP in pts with ISH► ► Indicated in ISH + Indicated in ISH + HF, Proteinuria, HF, Proteinuria, Diabetic Nephropathy..Diabetic Nephropathy..

→→ Before the Before the LIFE ISH sub-studyLIFE ISH sub-study

ARBsARBs

After the LIFE: ISHAfter the LIFE: ISH sub-study: sub-study:

♥ ♥ First trial demonstrating superiority ofFirst trial demonstrating superiority of

one anti-HT agent vs anotherone anti-HT agent vs another

♥ ♥ Losartan > AtenololLosartan > Atenolol in ↓ Stroke and in ↓ Stroke and

Cardio-vx MortalityCardio-vx Mortality

■■ New RecommendationsNew Recommendations of JNC including of JNC including

ARBs (Losartan) as First-line Tt??ARBs (Losartan) as First-line Tt??

NITRATESNITRATES

Vaso-dilatoryVaso-dilatory action on conduit vx action on conduit vx

May alter timing of reflected pr. wavesMay alter timing of reflected pr. waves

P.O.: P.O.: ↓ SBP↓ SBP without sign. changes in DBP without sign. changes in DBP

Well tolerated in elderlyWell tolerated in elderly

Advantageous in pts with Advantageous in pts with anginaangina

No large and randomised trials.No large and randomised trials.

αα ADRENERGIC BLOCKERS ADRENERGIC BLOCKERS

NOT recommendedNOT recommended as first-line agents by as first-line agents by

JNC VI:JNC VI:

↑ ↑ Co-vx eventsCo-vx events

↑ ↑ Congestive HFCongestive HF

Compared with other agents.Compared with other agents.

RECOMMENDATIONRECOMMENDATION

In all cases, decisions and regimens mustIn all cases, decisions and regimens must

be institued and tailored in accord with a be institued and tailored in accord with a

patient’s other comorbid conditions and patient’s other comorbid conditions and

responses to medication.responses to medication.

THANK YOU FOR YOUR ATTENTIONTHANK YOU FOR YOUR ATTENTION