COVERAM BP Decrease, Central Aortic and Synergy
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Transcript of COVERAM BP Decrease, Central Aortic and Synergy
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Fixed Combination in
Hypertension,
any radical change?
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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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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
Perindopril+Amlodipine
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In patients uncontrolled on monotherapy
Bahl VK et al. J hypertens. 2010;28():e98
BP Reduction
Perindopril+Amlodipine
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In patients uncontrolled on combinations
Bahl VK et al. J hypertens. 2010;28():e98
BP Reduction
Perindopril+Amlodipine
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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
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-50
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-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
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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