11 rencontres biomédicale lLIR Tabassonme Simon

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2ND INTERNATIONAL RESEARCH MEETING
4 JUNE 2010- HÔTEL DE MARIGNY PARIS

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11 rencontres biomédicale lLIR Tabassonme Simon

  1. 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. 2. <ul><li>Exhaustive, accurate </li></ul><ul><li>Complete Characterisation </li></ul><ul><li>All Drugs </li></ul><ul><li>Comprehensive Follow-up </li></ul><ul><li>In site Monitoring of data </li></ul>Experiences from previous networks in AMI USIC (1995 ,2000) DNA Bank Serum Bank <ul><li>Management policies, </li></ul><ul><li>Pharmacoepidemiology </li></ul><ul><li>Biomarkers </li></ul>
  3. 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. 4. Fast-MI 2005 : Nationwide Survey in AMI <ul><li>223 Intensive care Units (> 65% all ICUs) </li></ul><ul><ul><li>University, General hospitals, Private clinics </li></ul></ul><ul><ul><li>Consecutive AMI patients (Oct.-Nov. 2005) </li></ul></ul>DNA = 2430 pts Serum = 1065 pts <ul><li>3670 pts (1316 diabetic pts) </li></ul><ul><li>> 400 phenotype variables </li></ul><ul><li>All drugs (Type,dose, before, during, after Hospital. </li></ul><ul><li>Follow-up (5 yrs): 99.2% at 1yr, 97.8% at 2yrs. </li></ul>
  5. 5. Absorption : ABCB1 Metabolism: CYP2C19
  6. 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. 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. 8. sPLA2 activity and PLA2 G2A haplotypes sPLA2 Genetic Variant Serum levels of sPLA2 activity YES
  9. 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. 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. 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. 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.

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