1. The document discusses personalized medicine in cardiology, specifically focusing on treatment with clopidogrel in high-risk cardiovascular patients. It notes there is significant variability between individuals in treatment effectiveness and side effects. 2. Clopidogrel resistance is shown to affect 31-63% of patients within 2-24 hours depending on the time period studied. Certain high-risk groups like seniors, diabetics, and those with renal insufficiency are more likely to experience resistance. 3. Aldosterone levels are presented as a potential biomarker for outcomes in STEMI patients undergoing primary PCI. Studies show higher admission aldosterone levels correlate with reduced survival. Blocking aldosterone's lethal effects may improve outcomes

1. Médecine personnalisée en Cardiologie
« Personnalized medecine in cardiology »
Johanne Silvain, MD-PhD
Pitié-Salpêtrière Hospital
Paris – France
INSERM UMRS937
http://www.action-coeur.org/
3ème journée ARC et TEC , 25 Novembre 2011

2. « If it were not for the great variability among individuals,
medicine might as well be a science and not an art »
William Osler. The principles and pratice of Medicine, 1892
Effet indésirable Absence d’effet
Effet thérapeutique

3. 1- Traitement par clopidogrel chez les
patients à haut risque cardiovasculaire

4. Therapeutic in ACS ?
Mouse Models of In Vivo Thrombosis. Thrombus in STEMI patients.
1- Platelets antiplatelet agents CLOPIDOGREL
2- Thrombin anticoagulant
(PLAVIX™)
3- Fibrin fibers fibrinolytics
Weisel JW et al . Science 2009

5. The First Clopidogrel Resistance Study (300 mg)
A “Fingerprint” of Clopidogrel Response Variability
2 Hours 24 Hours
24 Resistance = 63% Resistance Resistance = 31%
Resistance 20
Patients (%)
Patients (%)
12 10
≤ -30 (-20,-10] (0,10] (20,30] (40,50] >60 ≤ -30 (-20,-10] (0,10] (20,30] (40,50] >60
(-30,-20] (-10,0] (10,20] (30,40] (50,60] (-30,-20] (-10,0] (10,20] (30,40] (50,60]
 Aggregation (%)  Aggregation (%)
5 Days 30 Days
22 28
Resistance Resistance = 31% Resistance = 15%
11
14
Patients (%)
Patients (%)
Resistance
≤ -10 (-10,0] (0,10] (10,20] (20,30] (30,40] (40,50] (50,60] >60 ≤ -30 (-20,-10] (0,10] (20,30] (40,50] >60
(-30,-20] (-10,0] (10,20] (30,40] (50,60]
 Aggregation (%)
 Aggregation (%)
Gurbel PA, et al. Circulation. 2003

6. Clopidogrel : Black-Box Warning
Collet et al. Lancet 2008
Mega et al. NEJM 2008 Simon et al. NEJM 2008

7. 1- Traitement par clopidogrel chez les
patients à haut risque cardiovasculaire
2- Les Syndromes Coronaires Aigus

8. ACS High Risk Patients
Seniors
>75 y/o
STEMI
Renal
Insufficiency
Diabetics
Genetic Resistant
(2C19)

9. Renal Insufficiency
Creatinin Clearance <60ml/min
- 2,1% absolute risk - 6,0% absolute risk reduction in
reduction (NNT=48) mortality (NNT=17)
Montalescot and Silvain et al. Circulation 2010

10. Seniors (>75 y/o) and Clopidogrel ?
HPR under clopidogrel 75mg = 38.2%
Traitement des
personnes âgés ?
n= 1027 patients
Silvain et al. Eur Heart Journal 2011

11. 1- Traitement par clopidogrel chez les
patients à haut risque cardiovasculaire
2- Les Syndromes Coronaires Aigus
3- Aldostérone un biomarqueur
réversible ?

12. Survival according to admission aldosterone level in
patients undergoing primary PCI for STEMI
Beygui et al. Circulation. 2006

13. From bench to clinical trial

14. Aldosterone Lethal Effects Blocked in Acute STEMI Treated with or without
Reperfusion to Improve Outcome and Survival at Six months follow-up

15. Médecine personnalisée en Cardiologie
« Personnalized medecine in cardiology »
Johanne Silvain, MD-PhD
Pitié-Salpêtrière Hospital
Paris – France
INSERM UMRS937
http://www.action-coeur.org/
3ème journée ARC et TEC , 25 Novembre 2011