coveram bp decrease, central aortic and synergy

7/22/2019 COVERAM BP Decrease, Central Aortic and Synergy

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1

Fixed Combination in

Hypertension,

any radical change?


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2

2007 Guidelines for the management of hypertension J Hypertens 2007;25:1105 87

2007 ESHESC Recommendationsfor combining BP-lowering drugs

ASCOT


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3

CCB

Vasodilatation

ACEI

Increased secretion of

Na+ and water

ACEI-CCB Combination: Synergy for BP Lowering

VSMC

Ca++

X

ReninSNS

Ang II

Ang I

BP

Activation of

a1R

(VSMC)

Vasoconstriction

Reduced Na+scrtion

CCB X X

X


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Blood pressure evidence

The example of Perindopril+Amlodipine


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Early & Strong BP Reduction

Bahl UK. Fixed dose perindopril and amlodipine in moderate-to-severe hypertension.14th World Congress of Heart Disease 2008, Toronto, Canada.

Perindopril+Amlodipine

n= 1 250

> 160mmHg

n= 161

> 180mmHg


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Whatever the profile of hypertensive

patients

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

BP Reduction



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In patients uncontrolled on monotherapy

Bahl VK et al. J hypertens. 2010;28():e98

BP Reduction



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In patients uncontrolled on combinations

Bahl VK et al. J hypertens. 2010;28():e98

BP Reduction



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Bahl UK. Fixed dose perindopril and amlodipine in moderate-to-severe hypertension.

14th World Congress of Heart Disease 2008, Toronto, Canada.Poulter NR, Chang CL, Dahlof B, Gupta AK, Sever PS, Wedel H, on behalf of the ASCOT investigators.Evaluating the efficacy of the stepped-care anti-hypertensive strategies used in the Anglo-Scandinavian Cardiac Outcomes Trial BP Lowering Arm (ASCOT-BPLA).

Hypertension. 2008. OS11/1.

Comparison with landmark trial

-44

-27

-50

-40

-30

-20

-10

0

SBP DDP

-42

-23

-50

-40

-30

-20

-10

0

SBP DDP

BP decrease(mmHg)

n= 1 250 n= 19 342

Amlodipine 5mg + Perindopril 5mg Amlodipine 5/10mg+Perindopril 5/10mg


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Comparison with other drugs

Mourad JJ, et al. Curr Med Res Opin. 2010;26:2263-2276


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Blood pressure quality

The example of Perindopril-Amlodipine


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European Society of Cardiology:

1.Hurst M el al. Drugs. 2001;61(6):867-896. 2. Hernandez RH et al. Blood Press Monit. 2001;6(1):47-57.

3. McClellan KJ et al. Drugs. 2000;60(5):1123-1140. 4. Diamant M et al. J Hum Hypertens. 1999;13(6):405-412.

5. Zannad F et al. Am J Hypertens. 1996;9(7):633-643. 6. Gradman AH, et al. Circulation. 2005;111:1012-1018.

7. Neutel JM et al. J Clin Hypertens. (Greenwich). 2002;4(5):325-331. 8. Hermida RC et al. Hypertens. 2003;42(3):283-290.

Drugs which exert their antihypertensive effect over 24 hours

with a once-a-day administration should be preferred

70

69

70

70

78

50

80

3860

55

63

75

100

100

0 20 40 60 80 100

Perindopril

Amlodipine

Enalapril

Quinilapril

Ramipril

Lisinopril

Captopril

Lercanidipine

Felodipine

Losartan

Irbesartan

Olmesartan

Valsartan

Aliskiren

% T/P Ratio


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Stabilizes blood pressure to avoidexcessive BP variability 1,2

BP variability: main cause of CV events.3

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;375:895905.

/Perindopril


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Blood pressure quality

Central Aortic Blood Pressure and Cafe study


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What is central aortic blood pressure?

BP measured at the aortic level which reflects the pressure at

key organ level

Central aortic blood

pressure

Brachial blood pressure


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Normal central aortic BP

Outgoing wave = blood exiting

the heart via aorta

Reflected wave = back wave

ofblood returning to the heart.

This is dependent on the

stiffness of the artery.

Aortic root = The sum of theoutgoing and reflected wave


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Figure 1

Elevated central aortic BP

Outgoing wave remains the

same

Reflected wavewill travel

back more quickly due to

arterial stiffness.

This means that it will arrive

back at the heart earlier.

Aortic root pressure

will be higher & thus the

pressure at the key organs too


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LVH

3. in blood volumereturning to the heartduring diastole

= risk of ischaemia

2. Increase LV load

= LV hypertrophy

1. Higher overall pressure

= risk of target organ damage

eg stroke

Consequences of high central aortic BP

l l i


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Pulse Wave Analysis

140

70

Radial

Transfer

function

Central Aortic

140

70

Brachial Blood

Pressure

T i l O i


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Trial Overview

To examine the

difference betweenrecommended betablocker/thiazide versus

newer Perindopril/Amlodipine BP regimen

on central aortic BP

2,070 ASCOT patients

Average BP = 160/92

4yr follow-up


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Effective in reducing central aortic BP control

A central aorticSBP difference

of4.3 mmHg

Similar brachial BP

reductions

Central Aortic BP reduction is linked to areduction in CV events

Perindopril


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Unique lifesaving benefits

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

/Perindopril /Perindopril

Cardiovascular protection andmortality reduction stronger than

recommended regimen


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Synergy of ACEI + CCB

The synergistic action of Perindopril-Amlodipine

A i ti d f ti


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A synergistic mode of action

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.

Perindopril Amlodipine

A l d i id ff t


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A synergy also decreasing side effects

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.

ACE Inhibitor

Perindopril

Induction of relaxation

= Vasodilation

CCB

Amlodipine

Prevention of constriction

= Vasodilation

Red e kle ede i o i o ith CCB


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Reduces ankle edema in comparison with CCB

Messerli FH, et al. Am J Cardiol. 2000;86(11):1182-1187Ferrari, R. Current Med. Research & Opinion, 2008, 24 (12), 3543-3557

Amlodipine alone

Precapillary vasodilation=> oedema

Venous dilation hence normalisingintracapillary pressure

Perindopril-Amlodipine

Reduces ankle oedema


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Reduces ankle oedema

116

144

247

70

90

110

130

150

170

190

210

230

250

270

M 0 M 1 M 3

Numberofpa

tients

- 52%

Hatala et al.. Submitted to ESH 2010

Perindopril-Amlodipine

Perindopril + Amlodipine decreases oedema


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Perindopril + Amlodipine decreases oedema

Amlodipine

o ankle edema in 22% of patients

CCB-related ankle edema cannot be relieved

by diuretics

o only fluid retention Amlodipine + perindopril fixed combination in

STRONG Study

o ankle edema in 0.7%

Perindopril + Amlodipine decreases cough


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Perindopril + Amlodipine decreases cough

ACEI CCB

inhibit kininase II

bradykinin

stim. PLAz inhibit

stim. pulm. sensory C fibers

coughing inhibit

arachidonic acid

PGEz

Ca++- dep. releas

of glutamate atsolitary tract

nucleus

Perindopril in EUROPA study

cough in 2.7%Perind + amlo in STRONG Study cough in 1.5%

Perindopril + Amlodipine


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Perindopril + Amlodipine

Provides stronger BP reduction (40-63 mmHg)o Controls BP over 24 h

o Decreases central BP

Provides stronger life saving benefitsASCOT

Offers excellent safety

o Oedema 0.7%

o Cough 1.5%

Perindopril + Amlodipine is


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Perindopril + Amlodipine is

High BP patients > 160mmHgUncontrolled BP on Amlodipine


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Thank you


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Radical changein hypertension

coveram bp decrease, central aortic and synergy

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