Targeting Blood Pressure

for Cardiovascular Risk

Prevention
Dr. Aulia Sani, SpJP (K), FJCC, FIHA, FAsCC
Departemen Kardiologi dan Kedokteran Vaskuler
FKUI / Pusat Jantung Nasional Harapan Kita, Jakarta

CURICULUM
VITAE
NAMA
USIA
ISTRI
ANAK

:
:
:
:

Dr AULIA SANI SPJP ( K ),FJCC,FIHA

65 TAHUN
NY NERRY A SANI
2 PUTRI

PEKERJAAN :

STAFF PENGAJAR BAGIAN KARDIOLOGI & KEDOKTERAN

VASKULER FKUI / PUSAT JANTUNG NASIONAL HARAPAN
KITA
DIREKTUR PENUNJANG MEDIK & REHABILITASI PJNHK
1994-1998
DIRUT PJNHK TAHUN 1998 2005

ORGANISASI :

KETUA PERKUMPULAN VASKULER INDONESIA

DEWAN PEMBINA YAYASAN JANTUNG INDONESIA PUSAT SEJAK 2003
ANGGOTA PERKI
ANGGOTA IDI
ANGGOTA DEWAN PAKAR PDUI

PENDIDIKAN :

RESEARCH CARDIOLOGY ON HEART RESEARCH CENTER MELBOURNE

AUSTRALIA 1998
TRAINING HOSPITAL ON HOSPITAL FOR MEDICAL TRAINING ( JCNI, TOKYO
JPN )
SPAMEN / LAN RI 1998
ADVANCE CARDIOLOGY TRAINING IN TORANOMON HOSPITAL TOKYO
JAPAN 1994 1995.
CARDIAC REHABILITATION TRAINING IN HOEHENRIED HOSPITAL, BENRIED
GERMAN 1991.
PROGRAM STUDI ILMU PENYAKIT JANTUNG DAN PEMBULUH DARAH 19811984
TRAINING ON ADVANCE MULTISLISH CITY / SCAI ( SOCIETY CARDILOGY
ASSOSIATION ON INTERVENTION ) PHOENIC USA, FEEBRUARY 2006

Clinical history:
Hypertension is, very largely, an
asymptomatic condition until and
unless it is very severe

Contribution of CV Risk Factors to

Burden of Disease Mortality*
Blood pressure
Tobacco

Developing

Underweight
Alcohol
Cholesterol
Unsafe sex
Overweight
Unsafe water, sanitation,
hygiene
Low fruit and vegetable intake
Indoor smoke from solid fuels
Physical inactivity

Percentage of Mortality Attributable to Risk

Factors
*Based on The World Health Report 2003.
Yach et al. JAMA. 2004;291:2616-2622.

countries
Developed
countries

Hypertension With Other CV Risk

Factors Increases Risk of MI
2.9
(2.6-3.2)

2.4
(2.1-2.7)

1.9
(1.7-2.1)

Smk
(1)

DM
(2)

HTN
(3)

3.3
(2.8-3.8)

13.0
(10.7-15.9)

42.3
(33.2-54.0)

68.5
(53.0-88.6)

All 4

+Obes

182.9
333.7
(132.6-252.2) (230.2-483.9)

512
Odds Ratio (95% CI)

256
128
64
32
16
8
4
2
1
ApoB/A1 1+2+3
(4)

+PS

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.

All RFs

Billions of Dollars

Economic Burden of
Cardiovascular Disease in the US
Estimated for 2005
393.5
400
300

254.8

200
142.1
100

56.8

59.7
27.9

Heart
disease

Coronary
heart
disease

Stroke

Hypertensive Congestive
disease
heart
failure

American Heart Association. Heart Disease and Stroke Statistics2005 Update.

Total
CVD*

Benefit of Blood
pressure
Lowering

12 to 13 mm Hg Drop in Systolic BP
Reduces
4-Year Risk of CAD, Stroke, Mortality

Reduction in risk (%)

0%

-10%
-13%
P=0.005

-20%

-30%

-40%

-21%
P<0.0001

-25%
P<0.001

-37%
P<0.001

Meta-analysis of 10 randomized trials. He and Whelton, J

Hypertens, 1999.

Effect of Long-Term Modest

Reductions in CV Risk Factors
10%
Reduction
in BP

10%
Reduction
in TC

Emberson et al. Eur Heart J. 2004;25:484-491.

45%
Reduction
in CVD

Management of
Hypertension

The main objective in lowering

BP is to reduce the patients
absolute risk of premature
death and disease, primarily
by reducing their risk of
cardiovascular diseases.

Ogden LG,et al. Hypertension. 2000

Algorithm for Treatment of

Hypertension from JNC-7
Lifestyle Modifications

Not at Goal Blood Pressure (<140/90 mmHg)

(<130/80 mmHg for those with diabetes or chronic kidney disease)

Initial Drug Choices

Without Compelling
Indications

With Compelling
Indications

Stage 1 Hypertension

Stage 2 Hypertension

(SBP 140159 or DBP 9099

mmHg)
Thiazide-type diuretics for most.
May consider ACEI, ARB, BB, CCB,
or combination.

(SBP >160 or DBP >100 mmHg)

2-drug combination for most
(usually thiazide-type diuretic and
ACEI, or ARB, or BB, or CCB)

Not at Goal
Blood Pressure
Optimize dosages or add additional drugs
until goal blood pressure is achieved.
Consider consultation with hypertension
specialist.

Drug(s) for the compelling

indications
Other antihypertensive drugs
(diuretics, ACEI, ARB, BB, CCB)
as needed.

Classification and
Management
of BP from JNC-7
BP
Lifestyle
SBP*
DBP*
classificatio
modificati
mmHg mmHg
n
on
Normal

Initial drug therapy

Without compelling
indication

<120

and
<80

Encourage

Prehypertensi
on

120
139

or 80
89

Yes

No antihypertensive
drug indicated.

Stage 1
Hypertension

140
159

or 90
99

Yes

Thiazide-type diuretics
for most. May consider
ACEI, ARB, BB, CCB, or
combination.

Stage 2
Hypertension

>160

or
>100

Yes

Two-drug combination
for most (usually
thiazide-type diuretic
and ACEI or ARB or BB
*Treatment determined by highest BP category.
or CCB).

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.

With compelling
indications

Drug(s) for
compelling
indications.
Drug(s) for the
compelling
indications.
Other
antihypertensive
drugs (diuretics,
ACEI, ARB, BB,
CCB) as needed.

Definitions & classification of BP levels

(mmHg)
(2007 ESC/ESH guidelines)
Category
Systolic
Diastolic
Optimal
<120
and
< 80
Normal
120129 and/or
8084
High normal
130139 and/or
8589
Grade 1
140159 and/or
9099
Grade 2
160179 and/or
100109
Grade 3
180
and/or
110
Isolated systolic 140
and <90
hypertension
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.

Initiation of Antihypertensive
Treatment
Blood Pressure mmHg
Other risk factors,
OD
Or disease
No other risk
factors
1-2 risk factors
3 risk factors, MS,
or OD
Diabetes

Established CV
or renal disease

Normal

High Normal

Grade 1 HT

Grade 2 HT

Grade 3 HT

SBP 120-129

SBP 130-139

SBP 140-159

SBP 160-179

SBP 180

or DBP 80-84

or DBP 85-89

or DBP 90-99 or DBP 100-199 or DBP 110

No BP

No BP

intervention intervention
Low added
risk

Low added
risk

Lifestyle changes

Lifestyle changes &

consider drug
treatment

Lifestyle changes

Lifestyle changes
+ drug treatment

Lifestyle changes
+
Immediate drug
treatment

Lifestyle changes
+
Immediate drug
treatment

Lifestyle changes for

Lifestyle changes for
several months then drug several months then drug
treatment if BP
treatment if BP
uncontrolled
uncontrolled
Lifestyle changes for
several months then drug
treatment if BP
uncontrolled

Lifestyle changes
+
drug treatment
Lifestyle changes
+
Immediate drug
treatment

Lifestyle changes
+
Immediate drug
treatment

Lifestyle changes for

Lifestyle changes
several months then drug
+
treatment if BP
Immediate drug
uncontrolled
treatment

Lifestyle changes
+
drug treatment
Lifestyle changes
+
Immediate drug
treatment

Lifestyle changes
+
Immediate drug
treatment
Lifestyle changes
+
Immediate drug
treatment

ESH/ESC Guidelines 2007

Eur Heart Journal 2007

Majority of Hypertensive Patients Need

Multiple Medications for Effective
Management
More Than 1 Agent Is Usually Required to Get to BP Goal
More Than 1 Agent Is Usually Required to Get to BP Goal
IDNT (135/85 mm Hg)
UKPDS 83 (< 85 mm Hgdiastolic)
ABCD (<75 mm Hgdiastolic)
MDRD (<92 mm Hgmean arterial pressure)
HOT (<80 mm Hgdiastolic)
ALLHAT (<140/90 mm Hg)
Number of Agents

Multiple medications can increase the complexity of treatment

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.

Anti Hypertension
Combination (2007 ESC/ESH
Diuretic
guidelines)

-blockers

ARBs

-blockers

CCBs=CA
Antagonist

ACE inhibitors

Unmet Needs

Trends in awareness,treatment,
and control of High BP in adults
ages 18-74
National Health Ans Nutrition Examination
Survey, Percent

II
(19761980)

III(Phase
1
1988-91)

III(Phase
2
1991-94)

19992000

Awarenes
s

51

73

68

70

Treatment

31

55

54

59

Control

10

29

27

34

Sources: Unpublished data for 1999-2000 computed by M.Wolz,NHLBI

Hypertension control rates around the

world
<140/90 mmHg (%)
United States
27
France
24
Canada
22
Italy 9
Egypt 8
England
6
Korea 5
China 3
Poland
2

<160/95 mmHg (%)

Germany
23
Finland
21
Spain
20
Australia
19
Scotland
18
India
9
Zaire
3

Indonesia?

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

Whats the Importance in

Hypertension
management:
REACH THE TARGET
IMMEDIATELY

therapy : Which monotherapy

and
When to use combination
therapy

The mono therapy :

Inadequate, because the percentage of patient

requiring combination therapy to obtain
adequate BP control is elevated (only 22-24%
actually achieve BP goals with mono therapy in
clinical trials)
In fact, unwanted metabolic effects of some
AHDs are attenuated when used in combination,
in particular with drugs that suppress the RAS

Rationale of combination
therapy
There is a value to the use of drug combination,
not only to improve overall efficacy within and
between individuals but also to reduce dosedependent side effects
Multiple physiologic system contribute to BP
elevation, multiple drugs will be needed to
maintain BP control
Fixed-dose combinations are more acceptable
because the efficacy and tolerability

fixed-dose products should be considered for

first-line therapy

How to initiate pharmacological therapy :

Which monotherapy and
When to use combination therapy
The

conclusion :

Using combination, either free or fixed, from

the beginning of pharmacological therapy is
contemplated in both guidelines
Implementing this possibility will probably
contribute to improvements in BP control
due to the ability of a combination therapy
to lower BP

Drug combination
In clinical trials
The major challenge in the contemporary treatment
of hypertension is the prompt achievement and
long-term maintenance of BP levels that are low
enough to reduce the incidence of major CV
endpoints
Multidrug therapy has been necessary in
approximately 75% of hypertensive individuals
LIFE : >90% required more than one AHD
ALLHAT : only 26% of subjects were at goal with a
single agent

The goals of combination

To improve the long-term
efficacy and tolerability of drug
treatment
To facilitate the prompt
achievement of target BP
To increase predictability of
responses in heterogeneous
population

Tolerability
Uncontrolled BP

Poor
compliance

Increased
dose

Increase incidence
of adverse effects

The particularly efficacious twodrug combinations

A thiazide diuretic or CCB

+
ACEI or ARB or Beta-blocker

Fixed-dose combinations
The rationale :
Traditional teaching based on
maximum flexibility of dose
titration and that combination
make it difficult to ascertain the
cause of any side effect is of little
importance

Fixed-dose combinations
The rationale :
In contrast, the advantages of the
combination are significant :
Nonadherence to multidose-multidrug, fixeddose simplify the treatment regimen and
promote adherence
Cost less
Have been carefully studied and approved to
produce greater long-term BP reduction than
monotherpy

Fixed-dose combinations
Clinical use:
Most often as the second step
Low-dose combination is
an alternative strategy to the
traditional approach of increasing the
dose
Now likely that many fixed-dose
combination will receive indication
for initial treatment of hypertension

Fixed-dose combinations
Beta-blocker and thiazide :
2.5 mg and 6.25 mg is a low-dose
combination
BB are effective antihypertensive
agent and are preferred therapy in
ischemic heart disease
BB attenuate the RAAS activation
that accompanies the use of thiazide
diuretics
Thiazide also improves the
effectiveness of BB in blacks and
others with low-renin hypertension