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Remodelage et plaque d’athérome: intérêt des IEC à forte dose

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.

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Remodelage et plaque d’athérome: intérêt des IEC à forte dose

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  1. Remodelage et plaque d’athérome:intérêt des IEC à forte dose G. Derumeaux Lyon Conflit d'intérêt : Servier, Actelion, Sanofi-Aventis

  2. 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) • 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) • Agents and doses of proven efficacy for secondary prevention should be employed Guidelines on the management of stable angina. Eur Heart J 2006;27:1341-1381.

  3. Quelles sont les cibles ? Ischémie myocardique Remodelage ventriculaire Circulation coronaire Athérosclérose

  4. TASC Major underlying lesion of atherosclerosis : plaque 50% Coronary Events Stroke 30% 41% 68% Atherosclerosis = inflammatory process characterized by the formation of lipid-rich atheromatous plaques in the arterial wall Arteriopathy 39%

  5. Pathophysiological continuum underlying the cardiovascular continuum Central aortic pressures Pulse pressure Central wave reflection Pathophysiological continuum Large arteries stiffening Endothelial damage Mechanical fatigue Atherosclerosis From J Am Coll Cardiol 2001;37:975-84.

  6. 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

  7. New insights from PERSPECTIVE 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 Bruining N et al. Coron Artery Dis. 2009; 20: 409-414.

  8. ICUS Sub-Segmentation and Calcium Detection The amount of calcium per segment (Calcium content level): Positive Calcium frames X 100% CCL = Total frames PERSPECTIVE 3 cohorts detected: Bruining N et al. Coron Artery Dis. 2009; 20: 409-414.

  9. Perindopril placebo -0.03 -0.33 * Reduction of noncalcified coronary plaques’ size with perindopril PERSPECTIVE Change in plaque area (mm2) * P=0.04 for perindopril vs placebo Segments with CCL 0-25% N=242 N=298 Bruining N et al. Coron Artery Dis. 2009; 20: 409-414.

  10. New insights from PERSPECTIVE 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.

  11. Carotid distensibility (kPa.10-3) Carotid PP (mmHg) * NS NS 85 20 * 15 75 10 65 5 55 0 4 mg 8 mg 4 mg 8 mg ANOVA: Interaction P=0.014 ANOVA: Interaction P<0.05 DAPHNET: dose-dependent effects of perindopril on carotid artery function in diabetic patients …for a similar reduction in MBP (office and ABPM) Tropeano AI et al. Hypertension 2006 7 months Baseline

  12. Tissue ACE Mechanisms of coronary event prevention with perindopril Bradykinin mediated effects Angiotensin II mediated effects Vasodilation Remodelling impact Restoration of endothelial function Antiapoptotic effect Antiinflammatory effect Plaque stabilization Restoration of fibrinolytic balance Reduction in coronary events

  13. Quelles sont les cibles ? Ischémie et fonction myocardique Remodelage ventriculaire Circulation coronaire Athérosclérose

  14. La taille d’IDM est un puissant marqueur de risque CV Solomon SD, Circulation 2005

  15. Orn S, AJC 2007

  16. Le remodelage ventriculaire gauche

  17. Physiopathologie du remodelage myocardique

  18. Remodelage VG : facteurs pronostiques LVEDVI 120 vs >120 ml/m2 DT 150 vs <150 ms Vena contracta 0.4 vs 0.4 cm

  19. Fraction d’éjectionAmélioration du pronostic sous traitement Cintrom, Circulation 1993

  20. Effet du blocage du SRA sur le remodelage VG 60 PEACE QUIET EUROPA CAPTIN 50 CAST HOPE GISSI 3 FAMIS CONSENSUS 2 40 Mdie coronaire. Ins Card SAVE AIRE IDM 30 SOLVD CONSENSUS 1 55 60 70 Age (ans) FEVG (%)

  21. En faveur de Perindopril En faveur du placebo RRR(%) P 38 Décès, IC ou Remodelage <0,001 Mortalité totale 0 0,90 27 Hospitalisation pour IC 0,24 46 Remodelage <0,001 0,0 1,0 2,0 Critère primaire

  22. PREAMI : Effet sur le remodelage VG

  23. 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.

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