Download Echocardiographic indicators of ventricular asynchrony and patient

Remodelage et plaque d’athérome:
intérêt des IEC à forte dose
G. Derumeaux
Lyon
Conflit d'intérêt : Servier, Actelion, Sanofi-Aventis
ACE inhibitors are recommended for
secondary prevention in CAD
 In CAD patients with co-existing
indications for ACE inhibitors:
hypertension, heart failure, left
ventricular dysfunction, prior MI, or
diabetes (class I, level of evidence
A)
Remodelling
Ventricular dilation/
cognitive dysfunction
Myocardial
infarction &
stroke
Congestive heart failure/
secondary stroke
Microalbuminuria
Atherosclerosis
and LVH
Endothelial
dysfunction
Macroproteinuria
End-stage
heart disease,
Nephrotic
brain damage
proteinuria
and dementia
Cardio/
End-stage
renal cerebrovascular
death
disease
Hypertension risk factors
diabetes, obesity, elderly
 In all patients with angina and
proven coronary disease based on
benefits weighted against costs
and risks for side effects (class IIa,
level of evidence B)
CV death, MI, cardiac arrest
%
12
Placebo
8
 Agents and doses of proven
efficacy for secondary prevention
should be employed
Perindopril 8mg
RRR -20%
P = 0.0003
4
0
0
1
2
Guidelines on the management of stable angina. Eur Heart J 2006;27:1341-1381.
3
4
5
Years
Quelles sont les cibles ?
Circulation
coronaire
Athérosclérose
Ischémie
myocardique
Remodelage
ventriculaire
Major underlyingTASC
lesion of atherosclerosis :
plaque
Stroke
41%
50%
30%
Atherosclerosis = inflammatory
process characterized by the
formation of lipid-rich
atheromatous plaques in the
arterial wall
Arteriopathy
39%
Coronary
Events
68%
Pathophysiological continuum underlying the
cardiovascular continuum
Central wave
reflection
Large arteries
stiffening
Central aortic pressures
Pathophysiological
continuum
Pulse pressure
Endothelial damage
Mechanical fatigue
Atherosclerosis
From J Am Coll Cardiol 2001;37:975-84.
Remodelage vasculaire
IVUS accurately measures the
coronary lumen dimension
IVUS allows for assessment of
eccentric lesions, coronary
remodelling, and progression or
regression of atherosclerotic
plaque
With IVUS, more detailed
plaque characterization with
differentiation of fibrocellular,
lipid-rich, and calcified regions is
feasible
König A et al ; Heart 2007
PERSPECTIVE
New insights from PERSPECTIVE
To test the hypothesis that the degree of calcification in plaques affects
the outcome of longitudinal ICUS driven progression-regression studies.
ICUS
Sub-Segmentation
and Calcium Detection
Normal coronary
artery (distal
reference)
Bruining N et al. Coron Artery Dis. 2009; 20: 409-414.
Atherosclerotic
plaque in coronary
artery
PERSPECTIVE
ICUS Sub-Segmentation and
Calcium Detection
The amount of calcium per segment
(Calcium content level):
Positive Calcium frames
X 100%
CCL =
Total frames
3 cohorts detected:
Bruining N et al. Coron Artery Dis. 2009; 20: 409-414.
CCL
N segments (%)
0-25%
540 (76%)
25-50%
73 (10%)
50-100%
98 (13%)
Reduction of noncalcified coronary
plaques’ size with perindopril
PERSPECTIVE
Change in plaque area (mm2)
Perindopril
placebo
0
-0.03
-0,05
* P=0.04 for perindopril
vs placebo
-0,1
-0,15
-0,2
-0,25
-0,3
-0,35
Segments with CCL
0-25%
-0.33
*
N=242
Bruining N et al. Coron Artery Dis. 2009; 20: 409-414.
N=298
PERSPECTIVE
New insights from PERSPECTIVE
Non-calcified plaques are amenable
to regression, with treatment of the
ACE inhibitor Perindopril, while
heavily calcified plaques are subject
to progression.
Bruining N et al. Coron Artery Dis. 2009; 20: 409-414.
DAPHNET: dose-dependent effects of perindopril
on carotid artery function in diabetic patients
Carotid distensibility
Carotid PP
(kPa.10-3)
(mmHg)
20
NS
*
85
NS
*
15
75
10
65
5
55
0
4 mg
8 mg
ANOVA:
Interaction P=0.014
4 mg
8 mg
ANOVA:
Interaction P<0.05
…for a similar reduction in MBP (office and ABPM)
Tropeano AI et al. Hypertension 2006
Baseline
7 months
Mechanisms of coronary event prevention
with perindopril
Bradykinin mediated
effects
Vasodilation
Remodelling
impact
Antiinflammatory
effect
Tissue
ACE
Angiotensin II
mediated effects
Restoration of
endothelial function
Restoration of
fibrinolytic balance
Reduction in coronary events
Antiapoptotic
effect
Plaque
stabilization
Quelles sont les cibles ?
Circulation
coronaire
Athérosclérose
Ischémie et
fonction
myocardique
Remodelage
ventriculaire
La taille d’IDM est un puissant marqueur de risque CV
Solomon SD, Circulation 2005
Orn S, AJC 2007
Le remodelage ventriculaire gauche
Physiopathologie du remodelage myocardique
Remodelage VG : facteurs pronostiques
LVEDVI
120 vs >120 ml/m2
DT
150 vs <150 ms
Vena contracta
0.4 vs 0.4 cm
Fraction d’éjection
Amélioration du pronostic sous traitement
Cintrom, Circulation 1993
Effet du blocage du SRA sur le remodelage VG
FEVG (%)
60
PEACE
QUIET
EUROPA
CAPTIN
50
CAST
GISSI 3 HOPE
FAMIS
CONSENSUS 2
40
Mdie coronaire.
Ins Card
SAVE
30
SOLVD
55
60
IDM
AIRE
CONSENSUS 1
70
Age (ans)
Critère primaire
En faveur En faveur
RRR
de Perindopril du placebo (%)
P
38
<0,001
0
0,90
Hospitalisation pour IC
27
0,24
Remodelage
46
<0,001
Décès, IC ou Remodelage
Mortalité totale
0,0
1,0
2,0
PREAMI : Effet sur le remodelage VG
Conclusion
From vulnerable plaque to vulnerable patient…
 In the PERSPECTIVE substudy of
EUROPA, ACE inhibition with high
dose of perindopril promoted
regression of non-calcified plaques
 Together with previously shown
vascular properties of perindopril,
these effects may underpin the
differential results of ACE inhibitor
trials in CAD
 “The earlier, the better” initiation of
therapy should be considered in
hypertension and CAD patients for
the prevention of CV events.