Managing ISOLATED SYSTOLIC HYPERTENION in the Elderly
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Transcript of Managing ISOLATED SYSTOLIC HYPERTENION in the Elderly
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
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TN
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(%)
Fai
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s b
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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