coveram-symcard-dr-yerizal.pdf

47 

Loading.... (view fulltext now)

Loading....

Loading....

Loading....

Loading....

Full text

(1)

Yerizal Karani

Yerizal Karani

The Rationale of Fixed Combination in

The Rationale of Fixed Combination in

the Management of Hypertension

the Management of Hypertension

(2)

Current Status of

Hypertension

(3)

Measure

n (95% CI)

Total number worldwide in 2000

972 million (957-987)

Total number in economically

developed countries in 2000

333 million (329-336)

Total number in economically

developing countries in 2000

639 million (625-654)

Total number worldwide in 2025

1.56 billion (1.54-1.58)

Kearney PM et al.

(4)

31.3 5.8 6.1 31.9 8.6 9 0 5 10 15 20 25 30 35 D D/O U Men Women

P

r

e

v

a

l

e

n

c

e

%

Dasar Diagnosis Dasar Diagnosis

Prevalence of HT based on gender

Prevalence of HT based on gender

(5)

Kannel WB. Kannel WB.JAMA. 1996;275:1571-1576. 1996;275:1571-1576.

0

0

10

10

20 20 30 30 40 40 50 50 Men Men 2.0 2.0 Women Women 2.2 2.2 Men Men 3.8 3.8 Women Women 2.6 2.6 Men Men 2.0 2.0 Women Women 3.7 3.7 Men Men 4.0 4.0 Women Women 3.0 3.0 Normotensie Normotensie Hypertensive Hypertensive Coronary Coronary disease disease Stroke

Stroke Peripheral arteryPeripheral artery disease disease Heart Heart failure failure Risk ratio: Risk ratio: Biennial Biennial age-adjusted rate adjusted rate per 1000 per 1000 patients patients

(6)

Cardiovascular mortality risk Cardiovascular mortality risk

0 0 2 2 4 4 8 8 115/75 135/85 155/95 175/105 115/75 135/85 155/95 175/105 6 6 Systolic BP/Diastolic BP (mmHg) Systolic BP/Diastolic BP (mmHg) 2X 2X risk risk 4X 4X risk risk 8X 8X risk risk 1X risk 1X risk

(7)

Takeda Chemical Industries, 1998 Takeda Chemical Industries, 1998

Treating hypertension reduces

Treating hypertension reduces cardiovascular

cardiovascular

Treating hypertension reduces

Treating hypertension reduces cardiovascular

cardiovascular

morbidity and mortality

morbidity and mortality

morbidity and mortality

morbidity and mortality

‘‘

‘‘Older’ patients (mean >65 years)Older’ patients (mean >65 years)Older’ patients (mean >65 years)Older’ patients (mean >65 years) ‘‘

‘‘

Younger’ patients (<65 years) Younger’ patients (<65 years) Younger’ patients (<65 years) Younger’ patients (<65 years)

* p<0.05; ** p<0.01; *** p<0.001 * p<0.05; ** p<0.01; *** p<0.001 * p<0.05; ** p<0.01; *** p<0.001 * p<0.05; ** p<0.01; *** p<0.001 Gueyffier Gueyffier Gueyffier Gueyffier et al (1996)et al (1996)et al (1996)et al (1996) –– ––80808080 –– ––60606060 –– ––40404040 –– ––20202020 0 0 0

0 CHFCHFCHFCHF StrokeStrokeStrokeStroke

CV CV CV CV mortality mortality mortality mortality Major Major Major Major coronary coronary coronary coronary event event event

event All deathsAll deathsAll deathsAll deaths

***

***

***

***

***

***

***

***

***

***

***

***

***

***

***

***

**

**

**

**

**

**

Relative risk (%)

Relative risk (%)

Relative risk (%)

Relative risk (%)

7

7

(8)

HT treatment

HT treatment

Treatment of CV risk factors / TOD Treatment of CV risk factors / TOD

Management associated clinical conditions Management associated clinical conditions

(9)

-

Awareness

70 %

11 % aware, but not treated

-

Treatment

59 %

25 % treated, but not controlled

-

Control

34 %

}

}

}

}

AS 2011 AS 2011

(10)

-Adequately treated -Adequately treated 79,4 79,4 85,3 85,3 50,9 50,9 -Treated cases -Treated cases 12,0 12,0 11,3 11,3 43,9 43,9 -Newly discovered -Newly discovered 88,0 88,0 88,7 88,7 56,1 56,1 -Awareness of -Awareness of responders responders 2,5 2,5 3,2 3,2 -Borderline hypertension -Borderline hypertension 17,9 17,9 16,9 16,9 14,9 14,9 -Prevalence of -Prevalence of hypertension hypertension Survey 2000 Survey 2000 (%) (%) Survey 1993 Survey 1993 (%) (%) Survey1988 Survey1988 (%) (%)

(11)

AS 2011 AS 2011

(12)

BP GOAL

BP GOAL

Monotherapy

Monotherapy

42-59%

42-59%

Combined therapy

Combined therapy

54-70%

54-70%

ALLHAT

ALLHAT

>50%

(13)

Lifestyle modifications Lifestyle modifications

Not at goal blood pressure (<140/90 mmHg) Not at goal blood pressure (<140/90 mmHg)

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

Initial drug choices Initial drug choices

Without compelling Without compelling indications indications With compelling With compelling indications indications Stage 1 hypertension Stage 1 hypertension (SBP 140-159 or DBP (SBP 140-159 or DBP 90-99 mmHg) 90-99 mmHg) Thiazide-ty

Thiazide-type pe diureticsdiuretics for most. May consider for most. May consider ACE-I

ACE-I, ARB, BB,, ARB, BB,CCBCCB or combination or combination Stage 2 hypertension Stage 2 hypertension (SBP (SBP 160 or DBP160 or DBP 100 mmHg)100 mmHg) Two-drug combination for Two-drug combination for most (usually thiazide-type most (usually thiazide-type diuretic and

diuretic andACE-IACE-I or or ARB, or BB, or ARB, or BB, orCCBCCB))

Drug(s) for the Drug(s) for the

compelling indications compelling indications Other antihypertensive Other antihypertensive Drugs (diuretics, Drugs (diuretics,ACE-IACE-I,, ARB, BB,

ARB, BB,CCBCCB) as needed) as needed

Not at blood pressure goal Not at blood pressure goal Optimize dosages or add additional drugs until

Optimize dosages or add additional drugs until goal blood pressure is achieved.goal blood pressure is achieved. Consider consultation with hypertension specialist.

Consider consultation with hypertension specialist.

SBP

SBP, systolic , systolic blood blood pressure; DBPpressure; DBP, diastolic , diastolic blood blood pressure; ACE-I,pressure; ACE-I, angiotensin-converting enzyme inhibitor; AR

angiotensin-converting enzyme inhibitor; ARB, angiotensin II reB, angiotensin II receptorceptor blocker; BB, beta-blocker; CCB, calcium-channel blocker

(14)

HYPERTENSION

HYPERTENSION

- COMPLEX

- COMPLEX DISORDERS

DISORDERS

- MULTIPLE PATHOGENETIC FACTORS

- MULTIPLE PATHOGENETIC FACTORS

( INCREASED BLOOD VOLUME,

( INCREASED BLOOD VOLUME,

VASOCONSTRICTION,

VASOCONSTRICTION,

OVERACTIVITY SNS AND RAAS )

OVERACTIVITY SNS AND RAAS )

(15)

ADDITIVE

COMPLIMENTARY

ADDITIVE

COMPLIMENTARY

EFFECT

PROPERTIES

EFFECT

PROPERTIES

ADVERSE EFFECTS

ADVERSE EFFECTS

LOWER DOSAGE

LOWER DOSAGE

OF EACH DRUGS

OF EACH DRUGS

OF EACH DRUG

OF EACH DRUG

NEUTRALIZED

NEUTRALIZED

-

- SIDE

SIDE EFFECTS

EFFECTS

QUALITY OF LIFE

QUALITY OF LIFE

COMPLIANCE

-COMPLIANCE -

Better BP controll

Better BP controll

2

2

AS 2011 AS 2011

(16)

RESPONSE

RESPONSE RATE

RATE TO

TO THERAPY

THERAPY

FROM

FROM 40

40 %-50

%-50 %

% TO

TO 70%-80%

70%-80%

RACIAL

RACIAL AND

AND AGE

AGE DIFFERENCES

DIFFERENCES

IN RESPONSE TO INDIVIDUAL

IN RESPONSE TO INDIVIDUAL

THERAPY

ELIMINATED

THERAPY

ELIMINATED

OFFICE

OFFICE VISITS

VISITS

COST

COST

SIDE

SIDE EFFECTS

EFFECTS

(17)

Can we improve BP control rates ?

Can we improve BP control rates ?

Gupta A, et al. Hypertension 2010; 55:399-407

(18)

Can we improve compliance rates ?

Can we improve compliance rates ?

Gupta A, et al. Hypertension 2010; 55:399-407

(19)

Primary Target RAAS

Primary Target RAAS

((

A

A

CEI/

CEI/

A

A

RB,

RB,

ß

ß

B

B

lockers

lockers

))

Low Renin States

Low Renin States

((

C

C

CB,

CB,

D

D

iuretic )

iuretic )

AS 2011 AS 2011

(20)

COMBINATION THERAPY

COMBINATION THERAPY

SHOULD BE

SHOULD BE

EFFECTIVE

EFFECTIVE

WELL

WELL TOLERA

TOLERATED

TED

POSITIVE

POSITIVE /

/ NEUTRAL

NEUTRAL EFFECTS

EFFECTS

on metabolic parameters

on metabolic parameters

and concomitant

and concomitant

diseases / risk factors

diseases / risk factors

(21)

The synergistic action of

(22)

CCB CCB

Vasodilatation

Vasodilatation

ACEI ACEI Increased secretion of Increased secretion of

ACEI-CCB

ACEI-CCB Combinatio

Combination:

n: Synergy

Synergy for

for BP

BP Lowering

Lowering

VSMC VSMC Ca++

X

X

Renin 

SNS

Ang II

Ang I

BP

BP

Activation of a

1R

(VSMC) Vasoconstriction Vasoconstriction Reduced Na+ Reduced Na+ sécrétion sécrétion CCB CCB

X

X

X

X

X

X

(23)

Ferrari R. Optimizing the treatment of hypertension and stable coronary artery disease:

clinical evidence for fixed-combination perindopril/amlodipine. Curr Med Res Opin. 2008;24:3543-3557.

A Synergy

(24)

Reduces ankle edema in

Reduces ankle edema in

comparison with CCB

comparison with CCB

Amlodipine alone Amlodipine alone Precapillary vasodilation Precapillary vasodilation => oedema => oedema

Venous dilation hence normalising Venous dilation hence normalising

intracapillary pressure intracapillary pressure Perindopril-Amlodipine Perindopril-Amlodipine

(25)

Less peripheral oedema with a CCB/RAS combination

Less peripheral oedema with a CCB/RAS combination

than with a CCB

than with a CCB monotherapy

monotherapy

Makani H, Bangalore S, Romero J et al.

Am J Med.

(26)

ACE inhibitor/CCB combination reduces cough in

ACE inhibitor/CCB combination reduces cough in

comparison with

comparison with ACE inhibitor alone

ACE inhibitor alone

Elimination of cough

(27)

Perindopril + Amlodipine decreases cough

Perindopril + Amlodipine decreases cough

ACEI ACEI CCBCCB inhibit kininase II inhibit kininase II bradykinin bradykinin stim. PLA

stim. PLAzz inhibitinhibit

stim. pulm. sensory C fibers stim. pulm. sensory C fibers

coughing inhibit coughing inhibit

arachidonic acid

arachidonic acid

PGE

PGE

zz

Ca

Ca

++++

- dep. releas

- dep. releas

of glutamate at

of glutamate at

solitary tract

solitary tract

nucleus

nucleus

Perindopril in EUROPA study

Perindopril in EUROPA study

cough in 2.7%

cough in 2.7%

Perind + amlo in STRONG Study

(28)

n= 1 250 n= 1 250 > 160mmHg > 160mmHg n= 161 n= 161 > 180mmHg > 180mmHg

(29)

Whatever the profile of

Whatever the profile of

hypertensive patients

hypertensive patients

Bahl VK et al. Am J Cardiovasc Drugs. 2009;9:135-142.

BP Reduction

BP Reduction

Perindopril

(30)

Comparison with landmark trial

Comparison with landmark trial

-44 -44 -25 -25 -50 -40 -30 -20 -10 0 S SBBP P DDDDPP -41 -41 -23 -23 -50 -40 -30 -20 -10 0 S SBBP P DDDDPP BP decrease (mmHg) n= 1 250 n= 19 342

(31)

24h BP: nocturnal 24h BP: nocturnal BP control BP control BP variability BP variability Brachial Brachial (clinic) BP (clinic) BP Central BP Central BP

Antihypertensive

efficacy

Components of antihypertensive efficacy…

Components of antihypertensive efficacy…

… have independent predictive value

… have independent predictive value

1. Ohkubo DT, et al. The Ohasama study. J Hypertens. 2000;18:847 –854. 2. Yamamoto Y, et al.Stroke. 1998; 29:570 –576.

3. Ohkubo T et al. J Hypertens. 2002;20:2183 –2189. 4. Stanton A, et al.Blood Press. 1993;2:289 –295. 5. Pedersen OL, et al. VALUE trial group. J Hypertens. 2007; 25:707 –712.

(32)

European Society of Cardiology:

European Society of Cardiology:

“ Drugs which exert

“ Drugs which exert their antihypertensive

their antihypertensive effect over 24 hours

effect over 24 hours

with a once-a-day administration should be

with a once-a-day administration should be preferred

preferred ”

Perindopril Perindopril11

(33)

Stabilizes blood pressure to avoid

Stabilizes blood pressure to avoid

excessive BP variability

excessive BP variability

1,21,2

BP variability: main cause of CV events

BP variability: main cause of CV events

..

33

1.Rothwell PM et al. Lancet Neurol. 2010;9(5):469-480 2. Rothwell PM et al. Lancet. 2010;375:938-948. 3. Rothwell PM et al. Lancet. 2010;375:895 –905.

/Perindopril /Perindopril

(34)

A central aortic

SBP difference

of 4.3 mmHg

4.3 mmHg

Similar brachial BP

reductions

Central Aortic BP reduction is linked to a

Central Aortic BP reduction is linked to a

reduction in CV events

reduction in CV events

Effective in reducing central aortic BP C

(35)

ASCOT insights: recent sub studies

ASCOT insights: recent sub studies

(36)

Fixed dose combinations:

Fixed dose combinations:

where is the evidence?

where is the evidence?

Among available fixed-dose combinations, which

combinations

- have been evaluated in morbidity-mortality trials?

- have been compared with other combinations?

- have proved clear superiority over comparators for

preventing CV events and mortality?

(37)

Only ASCOT shows life saving evidence

Only ASCOT shows life saving evidence

No: Nonsignificant

1. Dahlöf B et al. Lancet. 2005:366;895-906. 2. Pepite CJ. JAMA. 2003;290:2805-2816. 3. Jamerson K et al. N Engl J Med. 2008;359:2417-2428.

No No

No No

No No

No No

Among ACEi +

(38)

Valsartan/amlodipine

Telmisartan/amlodipine

Olmesartan/amlodipine

International Guidelin

(39)

ASCOT-BPLA

ASCOT-BPLA

www.ascotstudy.org

atenolol ±

bendroflumethiazide

amlodipine ±

perindopril

19,342

hypertensive

patients

PROBE

design

ASCOT-BPLA

ASCOT-BPLA

placebo

atorvastatin

10 mg

Double-blind

ASCOT-LLA

ASCOT-LLA

10,305 patients

TC ≤ 6.5 mmol/L (250 mg/dL)

Investigator-led, multinational

Investigator-led, multinational

randomised controlled trial

randomised controlled trial

(40)

ASCOT-BPLA: su

ASCOT-BPLA: summary of all end points

mmary of all end points

Primary

Primary

Non-fatal MI (incl silent) + fatal CHD

Secondary Secondary

Non-fatal MI (exc. Silent) + fatal CHD Total coronary end point

Total CV event and procedures All-cause mortality

Cardiovascular mortality Fatal and non-fatal stroke Fatal and non-fatal heart failure

Tertiary Tertiary

Silent MI Unstable angina Chronic stable angina Peripheral arterial disease Life-threatening arrhythmias New-onset diabetes mellitus New-onset renal impairment

Post hoc Post hoc

Primary end point + coronary revasc procs CV death + MI + stroke Unadjusted HR (95% CI) Unadjusted HR (95% CI) 0.90 (0.79-1.02) 0.87 (0.76-1.00) 0.87 (0.79-0.96) 0.84 (0.78-0.90) 0.89 (0.81-0.99) 0.76 (0.65-0.90) 0.77 (0.66-0.89) 0.84 (0.66-1.05) 1.27 (0.80-2.00) 0.68 (0.51-0.92) 0.98 (0.81-1.19) 0.65 (0.52-0.81) 1.07 (0.62-1.85) 0.70 (0.63-.078) 0.85 (0.75-0.97) 0.86 (0.77-0.96) 0.84 (0.76-0.92)

(41)

Cardiovascular protection and mortality

Cardiovascular protection and mortality

reduction stronger than classical regimen

reduction stronger than classical regimen

Dahlöf B et al. Lancet. 2005:366;895-906.

/Perindopril

(42)

Cardiovascular protection and

Cardiovascular protection and

mortality

(43)

Greatest synergy of Coversyl/CCB in CAD patients

Greatest synergy of Coversyl/CCB in CAD patients

(44)

A synergistic mode of action

A synergistic mode of action

Perindopril

(45)

Only 3 clinical trials in hypertension

Only 3 clinical trials in hypertension

decrease mortality

decrease mortality

11

1.RR: relative risk. NS: not significant. HCTZ: hydrochlorothiazide. ARB: angiotensin receptor blocker. ACEi: angiotensin-converting enzyme inhibitors. BFTZ: bendroflumethiazide Mourad JJ et al. J Hypertens. 2010;28:e98-e99. 2. Lithell H et al. J Hypertens. 2003;21:875-886. 3. Yui Y et al. Hypertens Res. 2004;27:181-191.

4. Schrader J et al. Stroke. 2005;36:1218-1226. 5. Kasanuki H et al. Eur Heart J. 2009;30:1203-1212. Principal reports of the morbidity-mortality trials using ARB or ACE-inhibitor as active treatment or as a comparison, since 01.01.2000. More than 66% of hypertensive patients identified in those trials. All-cause mortality: a prespecified end point (EP) or a composite of the primary or secondary EP, or reported in the principal study publication; and heart failure trials were excluded.

(46)

TAKE HOME MESSAGE

Provides strong BP reduction (40-63 mmHg)

o

Controls BP over 24 h

o

Decreases central BP

o

Decreases blood pressure variability

Saves life (ASCOT)

Offers excellent safety

(47)

Figure

Updating...

References

Updating...

Related subjects :