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Contribution of the French clinical networks to the understanding of physiopathology and pharmacogenetics in cardiovascular diseases : The FAST-MI illustration June, 4th, 2010 T.SIMON, MD, PhD Professor of Clinical Pharmacology UPMC-Paris 06 University,  Coordinator of the Clinical Research Unit URC-EST (APHP, Saint Antoine  Hospital)
[object Object],[object Object],[object Object],[object Object],[object Object],Experiences from previous networks in AMI  USIC (1995 ,2000) DNA  Bank Serum  Bank ,[object Object],[object Object],[object Object]
F rench registry of  A cute coronary syndrome with or without  ST  elevation (FAST-MI 2005)  N. Danchin HEGP, Paris V T. Simon   St Antoine, Paris VI Supported by institutional and private grants  :  CNAM (French Caisse Nationale  d’Assurance Maladie);  Pfizer, Servier
Fast-MI 2005 :  Nationwide Survey  in AMI ,[object Object],[object Object],[object Object],DNA = 2430  pts Serum = 1065 pts ,[object Object],[object Object],[object Object],[object Object]
Absorption :  ABCB1  Metabolism:   CYP2C19
Variations of secretory PLA2-IIa gene on sPLA2 activity and CV outcome at one year sPLA2 Genetic Variant Serum levels of  sPLA2 activity Events  (Death or MI) ? ? ?
Tertiles of sPLA2 activity and Death or MI Serum levels of  sPLA2 activity Events  (Death or MI) YES HR= 1 HR= 1.66 ;95%CI = 0.99-2.80 HR= 2.00 ; 95%CI =1.21-3.32
sPLA2 activity and PLA2 G2A haplotypes sPLA2  Genetic Variant Serum levels of  sPLA2 activity YES
PLA2 G2A haplotypes  and Death/MI at 1 year Patent Causal role of sPLA2 sPLA2 inhibitors  (Phase II,  Lancet, 2009 ) sPLA2 Genetic Variant sPLA2 activity Events  (Death or MI)
Fast-MI 2005 : Ongoing studies Publications and Patents 2 patents 32 Abstracts (AHA, ESC) 10 papers  (New Engl J Med 2009 Circ.,  4 under review, 4 prep.)  Biomarker studies UPMC-Paris 06,  INSERM (U970,  U 698 ) Paris V, Paris VII University University of California Pharmacogenetic ( Diabetes, CV drugs) UPMC-Paris 06,  Paris XI University Harvard Medical School Genetic Biomarkers UPMC-Paris 06 Tuffts University (Boston) University College (London) Genetic Consortium (Netherlands) DNA Bank Phenotyping Serum Bank
FAST-MI 2010 starting in October 2010 N. Danchin HEGP, Paris V T. Simon   St Antoine, Paris VI Supported by institutional and private grants  :  CNAM , CODDIM-Cardiovasculaire Ile de France ,  CeNGEPS, Dedicated Biobank Platforms of UPMC-Paris 06  Merck,  Lilly, Sanofi-Aventis
French Society of Cardiology Pr Tabassome Simon Saint Antoine Hospital DOLORES  (Chest Pain-SAMU ) 1 799 patients  (6 centers) OFICA (CHF) 1 869 patients  (170 centers)  ODIN (HF) 2 560 patients  (145 centers) ONACI (PCI  ) 801 137 patients  (101 centers) STIDEFIX  ( Resynchronisation ) 59 211 patients  (238 centers)  Registries of the French Society of Cardiology Registry team :  G.Mulak, B. Pace, E. Drouet, CRAs of URCEST, T. Simon, N. Danchin.

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11 rencontres biomédicale lLIR Tabassonme Simon

  • 1. Contribution of the French clinical networks to the understanding of physiopathology and pharmacogenetics in cardiovascular diseases : The FAST-MI illustration June, 4th, 2010 T.SIMON, MD, PhD Professor of Clinical Pharmacology UPMC-Paris 06 University, Coordinator of the Clinical Research Unit URC-EST (APHP, Saint Antoine Hospital)
  • 2.
  • 3. F rench registry of A cute coronary syndrome with or without ST elevation (FAST-MI 2005) N. Danchin HEGP, Paris V T. Simon St Antoine, Paris VI Supported by institutional and private grants : CNAM (French Caisse Nationale d’Assurance Maladie); Pfizer, Servier
  • 4.
  • 5. Absorption : ABCB1 Metabolism: CYP2C19
  • 6. Variations of secretory PLA2-IIa gene on sPLA2 activity and CV outcome at one year sPLA2 Genetic Variant Serum levels of sPLA2 activity Events (Death or MI) ? ? ?
  • 7. Tertiles of sPLA2 activity and Death or MI Serum levels of sPLA2 activity Events (Death or MI) YES HR= 1 HR= 1.66 ;95%CI = 0.99-2.80 HR= 2.00 ; 95%CI =1.21-3.32
  • 8. sPLA2 activity and PLA2 G2A haplotypes sPLA2 Genetic Variant Serum levels of sPLA2 activity YES
  • 9. PLA2 G2A haplotypes and Death/MI at 1 year Patent Causal role of sPLA2 sPLA2 inhibitors (Phase II, Lancet, 2009 ) sPLA2 Genetic Variant sPLA2 activity Events (Death or MI)
  • 10. Fast-MI 2005 : Ongoing studies Publications and Patents 2 patents 32 Abstracts (AHA, ESC) 10 papers (New Engl J Med 2009 Circ., 4 under review, 4 prep.) Biomarker studies UPMC-Paris 06, INSERM (U970, U 698 ) Paris V, Paris VII University University of California Pharmacogenetic ( Diabetes, CV drugs) UPMC-Paris 06, Paris XI University Harvard Medical School Genetic Biomarkers UPMC-Paris 06 Tuffts University (Boston) University College (London) Genetic Consortium (Netherlands) DNA Bank Phenotyping Serum Bank
  • 11. FAST-MI 2010 starting in October 2010 N. Danchin HEGP, Paris V T. Simon St Antoine, Paris VI Supported by institutional and private grants : CNAM , CODDIM-Cardiovasculaire Ile de France , CeNGEPS, Dedicated Biobank Platforms of UPMC-Paris 06 Merck, Lilly, Sanofi-Aventis
  • 12. French Society of Cardiology Pr Tabassome Simon Saint Antoine Hospital DOLORES (Chest Pain-SAMU ) 1 799 patients (6 centers) OFICA (CHF) 1 869 patients (170 centers) ODIN (HF) 2 560 patients (145 centers) ONACI (PCI ) 801 137 patients (101 centers) STIDEFIX ( Resynchronisation ) 59 211 patients (238 centers) Registries of the French Society of Cardiology Registry team : G.Mulak, B. Pace, E. Drouet, CRAs of URCEST, T. Simon, N. Danchin.