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Targeting Blood Pressure Targeting Blood Pressure for Cardiovascular Risk for Cardiovascular Risk
PreventionPrevention
Dr. Aulia Sani, SpJP (K), FJCC, FIHA, FAsCCDepartemen Kardiologi dan Kedokteran Vaskuler FKUI / Pusat Jantung Nasional Harapan Kita, Jakarta
Dr. Aulia Sani, SpJP (K), FJCC, FIHA, FAsCCDepartemen Kardiologi dan Kedokteran Vaskuler FKUI / Pusat Jantung Nasional Harapan Kita, Jakarta
NAMANAMA : Dr AULIA SANI SPJP ( K ),FJCC,FIHA : Dr AULIA SANI SPJP ( K ),FJCC,FIHA
USIAUSIA : 65 TAHUN : 65 TAHUN
ISTRIISTRI : NY NERRY A SANI : NY NERRY A SANI
ANAKANAK : 2 PUTRI: 2 PUTRI
PEKERJAAN :PEKERJAAN :
STAFF PENGAJAR BAGIAN KARDIOLOGI & KEDOKTERAN STAFF PENGAJAR BAGIAN KARDIOLOGI & KEDOKTERAN VASKULER FKUI / PUSAT JANTUNG NASIONAL HARAPAN VASKULER FKUI / PUSAT JANTUNG NASIONAL HARAPAN KITAKITA
DIREKTUR PENUNJANG MEDIK & REHABILITASI PJNHK DIREKTUR PENUNJANG MEDIK & REHABILITASI PJNHK 1994-19981994-1998
DIRUT PJNHK TAHUN 1998 – 2005DIRUT PJNHK TAHUN 1998 – 2005
CURICULUM VITAE
ORGANISASI :ORGANISASI :
KETUA PERKUMPULAN VASKULER INDONESIAKETUA PERKUMPULAN VASKULER INDONESIA DEWAN PEMBINA YAYASAN JANTUNG INDONESIA PUSAT SEJAK 2003DEWAN PEMBINA YAYASAN JANTUNG INDONESIA PUSAT SEJAK 2003 ANGGOTA PERKIANGGOTA PERKI ANGGOTA IDIANGGOTA IDI ANGGOTA DEWAN PAKAR PDUIANGGOTA DEWAN PAKAR PDUI
PENDIDIKAN :PENDIDIKAN :
RESEARCH CARDIOLOGY ON HEART RESEARCH CENTER MELBOURNE RESEARCH CARDIOLOGY ON HEART RESEARCH CENTER MELBOURNE AUSTRALIA 1998AUSTRALIA 1998
TRAINING HOSPITAL ON HOSPITAL FOR MEDICAL TRAINING ( JCNI, TOKYO TRAINING HOSPITAL ON HOSPITAL FOR MEDICAL TRAINING ( JCNI, TOKYO JPN )JPN )
SPAMEN / LAN RI 1998SPAMEN / LAN RI 1998 ADVANCE CARDIOLOGY TRAINING IN TORANOMON HOSPITAL TOKYO ADVANCE CARDIOLOGY TRAINING IN TORANOMON HOSPITAL TOKYO
JAPAN 1994 – 1995.JAPAN 1994 – 1995. CARDIAC REHABILITATION TRAINING IN HOEHENRIED HOSPITAL, BENRIED CARDIAC REHABILITATION TRAINING IN HOEHENRIED HOSPITAL, BENRIED
GERMAN 1991.GERMAN 1991. PROGRAM STUDI ILMU PENYAKIT JANTUNG DAN PEMBULUH DARAH 1981-PROGRAM STUDI ILMU PENYAKIT JANTUNG DAN PEMBULUH DARAH 1981-
19841984 TRAINING ON ADVANCE MULTISLISH CITY / SCAI ( SOCIETY CARDILOGY TRAINING ON ADVANCE MULTISLISH CITY / SCAI ( SOCIETY CARDILOGY
ASSOSIATION ON INTERVENTION ) PHOENIC USA, FEEBRUARY 2006ASSOSIATION ON INTERVENTION ) PHOENIC USA, FEEBRUARY 2006
Clinical history:Clinical history:
““Hypertension is, very largely, an Hypertension is, very largely, an asymptomatic condition until and asymptomatic condition until and
unless it is very severe”unless it is very severe”
Contribution of CV Risk Factors to Contribution of CV Risk Factors to Burden of Disease Mortality*Burden of Disease Mortality*
0 5 10 15 20
Percentage of Mortality Attributable to Risk Factors
*Based on The World Health Report 2003. Yach et al. JAMA. 2004;291:2616-2622.
Developing
countries Developed countries
Blood pressure
Tobacco
Underweight
Alcohol
Cholesterol
Unsafe sex
OverweightUnsafe water, sanitation,
hygieneLow fruit and vegetable intake
Indoor smoke from solid fuels
Physical inactivity
Hypertension With Other CV Risk Hypertension With Other CV Risk Factors Increases Risk of MIFactors Increases Risk of MI
Od
ds
Rat
io (
95%
CI)
Od
ds
Rat
io (
95%
CI)
512512
256256
128128
6464
3232
1616
88
44
22
11Smk(1)
DM(2)
HTN(3)
ApoB/A1(4)
1+2+3 All 4 +Obes +PS All RFs
2.92.9(2.6-3.2)(2.6-3.2)
2.42.4(2.1-2.7)(2.1-2.7)
1.91.9(1.7-2.1)(1.7-2.1)
3.33.3(2.8-3.8)(2.8-3.8)
13.013.0(10.7-15.9)(10.7-15.9)
42.342.3(33.2-54.0)(33.2-54.0)
68.568.5(53.0-88.6)(53.0-88.6)
1182.982.9(132.6-252.2)(132.6-252.2)
333.7333.7(230.2-483.9)(230.2-483.9)
Smk=smoking; DM=diabetes mellitus; HTN=Hypertension; Obes=abdominal obesity; PS=psychosocial; RF=risk factor; MI=myocardial infarction.Yusuf S et al. Lancet. 2004; 364:937-952.
Economic Burden of Economic Burden of Cardiovascular Disease in the US Cardiovascular Disease in the US
Estimated for 2005Estimated for 2005
American Heart Association. Heart Disease and Stroke Statistics—2005 Update.
Heart disease
Coronary heart
disease
Stroke Hypertensive disease
Congestive heart failure
Total CVD*
Bil
lio
ns
of
Do
llar
sB
illi
on
s o
f D
oll
ars
254.8
142.1
56.8 59.727.9
393.5
0
100
200
300
400
Benefit of Blood Benefit of Blood pressurepressureLoweringLowering
Meta-analysis of 10 randomized trials. He and Whelton, J
Hypertens, 1999.
12 to 13 mm Hg Drop in Systolic BP 12 to 13 mm Hg Drop in Systolic BP Reduces Reduces
4-Year Risk of CAD, Stroke, Mortality4-Year Risk of CAD, Stroke, Mortality
Red
uct
ion
in
ri
sk
(%)
0%
-20%
-30%
-10%
-40%
CHD Stroke CVD mortalityAll-causemortality
PP<0.0001<0.0001
PP=0.005=0.005
PP<0.001<0.001
-21%-21%
-37%-37%
-25%-25%
-13%-13%
PP<0.001<0.001
Effect of Long-Term Modest Effect of Long-Term Modest Reductions in CV Risk FactorsReductions in CV Risk Factors
Emberson et al. Emberson et al. Eur Heart J.Eur Heart J. 2004;25:484-491. 2004;25:484-491.
10% 10% ReductionReduction
in BPin BP
10% Reduction
in TC+45% 45%
ReductionReductionin CVDin CVD
=
Management of Management of Hypertension Hypertension
The main objective in lowering The main objective in lowering BP is toBP is to reduce the patient’s reduce the patient’s absolute risk of premature absolute risk of premature deathdeath and disease, primarily and disease, primarily by reducing their risk of by reducing their risk of cardiovascular diseases.cardiovascular diseases.
Ogden LG,et al.Ogden LG,et al. Hypertension Hypertension. 2000. 2000
Algorithm for Treatment of Algorithm for Treatment of Hypertension from JNC-7Hypertension from JNC-7
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.
Classification and Classification and Management Management
of BP from JNC-7of BP from JNC-7BP BP
classificatioclassificationn
SBP* SBP* mmHgmmHg
DBP* DBP* mmHgmmHg
Lifestyle Lifestyle modificatimodificati
onon
Initial drug therapyInitial drug therapy
Without compelling Without compelling indication indication
With compelling With compelling indicationsindications
NormalNormal <120<120 and and <80<80
EncourageEncourage
PrehypertensiPrehypertensionon
120120––139139
or 80or 80––8989
YesYes No antihypertensive No antihypertensive drug indicated.drug indicated.
Drug(s) for Drug(s) for compelling compelling indications. indications. ‡‡
Stage 1 Stage 1 HypertensionHypertension
140140––159159
or 90or 90––9999
YesYes Thiazide-type diuretics Thiazide-type diuretics for most. May consider for most. May consider ACEI, ARB, BB, CCB, or ACEI, ARB, BB, CCB, or combination.combination.
Drug(s) for the Drug(s) for the compelling compelling indications.indications.‡‡
Other Other antihypertensive antihypertensive drugs (diuretics, drugs (diuretics, ACEI, ARB, BB, ACEI, ARB, BB, CCB) as needed. CCB) as needed.
Stage 2 Stage 2 HypertensionHypertension
>>160160 or or >>100100
YesYes Two-drug combination Two-drug combination for mostfor most†† (usually (usually thiazide-type diuretic thiazide-type diuretic and ACEI or ARB or BB and ACEI or ARB or BB or CCB).or CCB).
*Treatment determined by highest BP category.†Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension.‡Treat patients with chronic kidney disease or diabetes to BP goal of <130/80 mmHg.
Definitions & classification of BP levels Definitions & classification of BP levels (mmHg)(mmHg)
(2007 ESC/ESH guidelines)(2007 ESC/ESH guidelines)
Category Category Systolic Systolic DiastolicDiastolicOptimal Optimal <120 <120 and and < 80 < 80Normal Normal 120–129 and/or 120–129 and/or 80–8480–84High normal High normal 130–139 and/or 130–139 and/or 85–8985–89Grade 1 Grade 1 140–159 and/or 140–159 and/or 90–9990–99Grade 2 Grade 2 160–179 and/or 160–179 and/or 100–109100–109Grade 3 ≥180 and/or Grade 3 ≥180 and/or ≥ 110≥ 110Isolated systolic Isolated systolic ≥ 140 and ≥ 140 and <90<90
hypertensionhypertension
Isolated systolic hypertension should be graded (1, 2,3) according to systolic blood pressure values in the ranges indicated, provided that diastolicvalues are ,90 mmHg. Grades 1, 2 and 3 correspond to classificationin mild, moderate and severe hypertension, respectively. These termshave been now omitted to avoid confusion with quantification of total cardiovascular risk.
Blood Pressure mmHgBlood Pressure mmHgOther risk factors,
OD
Or disease
Established CV or renal disease
No other risk factors
1-2 risk factors
≥3 risk factors, MS, or OD
Diabetes
Normal
SBP 120-129
or DBP 80-84
High Normal
SBP 130-139
or DBP 85-89
Grade 1 HT
SBP 140-159
or DBP 90-99
Grade 2 HT
SBP 160-179
or DBP 100-199
Grade 3 HT
SBP ≥180
or DBP ≥110
No BP
intervention
Lifestyle changes for several months then drug
treatment if BP uncontrolled
Lifestyle changes +
Immediate drug treatment
Low added risk
Low added risk
No BP
intervention
Lifestyle changes for several months then drug
treatment if BP uncontrolled
Lifestyle changes for several months then drug
treatment if BP uncontrolled
Lifestyle changes for several months then drug
treatment if BP uncontrolled
Lifestyle changes +
Immediate drug treatment
Lifestyle changes +
Immediate drug treatment
Lifestyle changes +
Immediate drug treatment
Lifestyle changes +
Immediate drug treatment
Lifestyle changes +
Immediate drug treatment
Lifestyle changes +
Immediate drug treatment
Lifestyle changes +
Immediate drug treatment
Lifestyle changes
Lifestyle changes
Lifestyle changes & consider drug
treatmentLifestyle changes
+
drug treatment
Lifestyle changes +
drug treatment
ESH/ESC Guidelines 2007 Eur Heart Journal 2007
Lifestyle changes + drug treatment
Initiation of Antihypertensive Initiation of Antihypertensive TreatmentTreatment
Majority of Hypertensive Patients Need Majority of Hypertensive Patients Need Multiple Medications for Effective Multiple Medications for Effective
ManagementManagement
Bakris et al. Am J Kidney Dis. 2000;36:646-661; Brenner et al. N Engl J Med. 2001;345: 861-869; Lewis et al. N Engl J Med. 2001;345:851-860; Cushman et al. J Clin Hypertens. 2002;4:393-404.
More Than 1 Agent Is Usually Required to Get to BP GoalMore Than 1 Agent Is Usually Required to Get to BP GoalMore Than 1 Agent Is Usually Required to Get to BP GoalMore Than 1 Agent Is Usually Required to Get to BP Goal
2,00
3,25
3,70
2,75
2,70
3,80
0 1 2 3 4
ALLHAT (<140/90 mm Hg)ALLHAT (<140/90 mm Hg)
HOT (<80 mm Hg–diastolic)HOT (<80 mm Hg–diastolic)
MDRD (<92 mm Hg–mean arterial pressure)MDRD (<92 mm Hg–mean arterial pressure)
ABCD (<75 mm Hg–diastolic)ABCD (<75 mm Hg–diastolic)
UUKKPDS 83 (< 85 mm Hg–diastolic)PDS 83 (< 85 mm Hg–diastolic)
IDNT (135/85 mm Hg)IDNT (135/85 mm Hg)
Number of Agents
Multiple medications can increase the complexity of treatmentMultiple medications can increase the complexity of treatmentMultiple medications can increase the complexity of treatmentMultiple medications can increase the complexity of treatment
Anti Hypertension Combination (2007 ESC/ESH
guidelines)Diuretic
ACE inhibitors
ARBs
CCBs=CA Antagonist
-blockers
-blockers
Unmet NeedsUnmet Needs
Trends in awareness,treatment, Trends in awareness,treatment, and control of High BP in adults and control of High BP in adults
ages 18-74ages 18-74National Health Ans Nutrition Examination National Health Ans Nutrition Examination Survey, PercentSurvey, Percent
IIII
(1976-(1976-1980)1980)
III(Phase III(Phase 11
1988-91)1988-91)
III(Phase III(Phase 22
1991-94)1991-94)1999-1999-20002000
AwarenesAwarenesss
5151 7373 6868 7070
TreatmentTreatment 3131 5555 5454 5959
ControlControl 1010 2929 2727 3434
Sources: Unpublished data for 1999-2000 computed by M.Wolz,NHLBI
Hypertension control rates around the Hypertension control rates around the worldworld
<140/90 mmHg (%)<140/90 mmHg (%)
United StatesUnited States 27 27
FranceFrance 24 24
CanadaCanada 2222
ItalyItaly 99
EgyptEgypt 88
EnglandEngland 66
KoreaKorea 55
ChinaChina 33
PolandPoland 2 2
<160/95 mmHg (%)
Germany 23
Finland 21
Spain 20
Australia 19
Scotland 18
India 9
Zaire 3
JNC VI. Arch Intern Med 1997;157:2413-2446; Joffres MR, et al. Am J Hypertens 1997;10:1097-1102; Colhoun HM, et al. J Hypertens 1998;16:747-752; Chamotin B, et al. Am J Hypertens 1998;11:759-762; Marques-Vidal P, et al. J Hum Hypertens 1997;11:213-220
Indonesia?
What’s the Importance in What’s the Importance in Hypertension Hypertension management:management:
REACH THE TARGET REACH THE TARGET IMMEDIATELYIMMEDIATELY
How to initiate pharmacological How to initiate pharmacological therapy : Which monotherapy therapy : Which monotherapy
andandWhen to use combination When to use combination
therapytherapy The mono therapy :The mono therapy :
– Inadequate, because the percentage of patient Inadequate, because the percentage of patient requiring combination therapy to obtain requiring combination therapy to obtain adequate BP control is elevated (only 22-24% adequate BP control is elevated (only 22-24% actually achieve BP goals with mono therapy in actually achieve BP goals with mono therapy in clinical trials) clinical trials)
– In fact, unwanted metabolic effects of some In fact, unwanted metabolic effects of some AHDs are attenuated when used in combination, AHDs are attenuated when used in combination, in particular with drugs that suppress the RASin particular with drugs that suppress the RAS
Rationale of combination Rationale of combination therapytherapy
There is a value to the use of drug There is a value to the use of drug combination, not only to improve overall combination, not only to improve overall efficacy within and between individuals but efficacy within and between individuals but also to reduce dose-dependent side effectsalso to reduce dose-dependent side effects
Multiple physiologic system contribute to BP Multiple physiologic system contribute to BP elevation, multiple drugs will be needed to elevation, multiple drugs will be needed to maintain BP controlmaintain BP control
Fixed-dose combinations are more acceptable Fixed-dose combinations are more acceptable because the efficacy and tolerability because the efficacy and tolerability
fixed-dose products should be considered fixed-dose products should be considered for first-line therapyfor first-line therapy
How to initiate pharmacological therapy : How to initiate pharmacological therapy : Which monotherapy andWhich monotherapy and
When to use combination therapyWhen to use combination therapy
The conclusion :The conclusion :– Using combination, either free or fixed, from Using combination, either free or fixed, from
the beginning of pharmacological therapy is the beginning of pharmacological therapy is contemplated in both guidelinescontemplated in both guidelines
– Implementing this possibility will probably Implementing this possibility will probably contribute to improvements in BP control contribute to improvements in BP control due to the ability of a combination therapy due to the ability of a combination therapy to lower BP to lower BP
Drug combinationDrug combination
In clinical trialsIn clinical trials The major challenge in the contemporary The major challenge in the contemporary
treatment of hypertension is the prompt treatment of hypertension is the prompt achievement and long-term maintenance of BP achievement and long-term maintenance of BP levels that are low enough to reduce the incidence levels that are low enough to reduce the incidence of major CV endpointsof major CV endpoints
Multidrug therapy has been necessary in Multidrug therapy has been necessary in approximately 75% of hypertensive individualsapproximately 75% of hypertensive individuals– LIFE : >90% required more than one AHDLIFE : >90% required more than one AHD– ALLHAT : only 26% of subjects were at goal with ALLHAT : only 26% of subjects were at goal with
a single agenta single agent
The goals of combinationThe goals of combination
To improve the long-term To improve the long-term efficacy and tolerability of drug efficacy and tolerability of drug treatmenttreatment
To facilitate the prompt To facilitate the prompt achievement of target BPachievement of target BP
To increase predictability of To increase predictability of responses in heterogeneous responses in heterogeneous populationpopulation
Tolerability Tolerability
Uncontrolled BPUncontrolled BP
Increased Increased dosedose
Poor Poor compliancecompliance
Increase incidence Increase incidence of adverse effectsof adverse effects
The particularly efficacious two-The particularly efficacious two-drug combinationsdrug combinations
A thiazide diuretic A thiazide diuretic oror CCB CCB
++ACEI ACEI oror ARB ARB oror Beta-blocker Beta-blocker
Fixed-dose combinationsFixed-dose combinations
The rationale :The rationale :Traditional teaching based on Traditional teaching based on
maximum flexibility of dose maximum flexibility of dose titration and that combination titration and that combination make it difficult to ascertain the make it difficult to ascertain the cause of any side effect is of little cause of any side effect is of little importanceimportance
Fixed-dose combinationsFixed-dose combinations
The rationale :The rationale : In contrast, the advantages of the In contrast, the advantages of the
combination are significant :combination are significant :– Nonadherence to multidose-multidrug, fixed-Nonadherence to multidose-multidrug, fixed-
dose simplify the treatment regimen and dose simplify the treatment regimen and promote adherencepromote adherence
– Cost lessCost less– Have been carefully studied and approved to Have been carefully studied and approved to
produce greater long-term BP reduction produce greater long-term BP reduction than monotherpythan monotherpy
Clinical use:Clinical use: Most often as the “second step”Most often as the “second step” ““Low-dose combination” is Low-dose combination” is
– an alternative strategy to the an alternative strategy to the traditional approach of increasing traditional approach of increasing the dose the dose
– Now likely that many fixed-dose Now likely that many fixed-dose combination will receive indication combination will receive indication for initial treatment of hypertension for initial treatment of hypertension
Fixed-dose combinationsFixed-dose combinations
Beta-blocker and thiazide :Beta-blocker and thiazide : 2.5 mg and 6.25 mg is a low-dose 2.5 mg and 6.25 mg is a low-dose
combinationcombination BB are effective antihypertensive BB are effective antihypertensive
agent and are preferred therapy in agent and are preferred therapy in ischemic heart diseaseischemic heart disease
BB attenuate the RAAS activation BB attenuate the RAAS activation that accompanies the use of thiazide that accompanies the use of thiazide diureticsdiuretics
Thiazide also improves the Thiazide also improves the effectiveness of BB in blacks and effectiveness of BB in blacks and others with low-renin hypertension others with low-renin hypertension
Fixed-dose combinationsFixed-dose combinations