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1. RNA en cardiologie: l’âge du silence
2. Aucun conflit d’intérêt
3. Maladies cardiovasculaires
4. Athérosclérose
5. Caracteristiques des lipoprotéines
6. Time-Exposure to LDL-C
7. Lowering cholesterol lowers CV events: first evidence
8. Time-Exposure to low LDL-C
9. Time-Exposure to low LDL-C
10. Evidence for efficacy of LDL-lowering therapies down to below 1.4 mmol/L (55 mg/dL)
11. PCSK9 mAb: Efficacy and safety
12. ESC/EAS 2019 Lipid Guidelines
13. Despite efficacious LDL-C lowering therapies: High and very high-risk patients are failing to achieve LDL-C goals
14. DA VINCI study demonstrates current gaps in reaching 2016 and 2019 ESC/EAS LDL-C goals
15. Perceived side effects are the leading cause of statin discontinuation
16. Therapy interruptions are observed with monoclonal antibodies directed against PCSK9
17. Fully human monoclonal antibody against PCSK9 inhibits PCSK9/LDL-R interaction
18. Approaches to reduce LDL-C levels
19. Gene-Protein Synthesis Non-coding RNAs
20. RNA Therapeutics Synthetic small RNA
21. RNA interference enables a cell to specifically shut down protein production
22. What is inclisiran ? Small interfering RNA
23. Mechanism of action GalNAc conjugation enables rapid uptake of inclisiran into hepatocytes via asialoglycoprotein receptor (ASGPR)
24. Inclisiran treatment Dose & administration
25. Inclisiran clinical studies ORION development program
26. Lowering PCSK9 with siPCSK9
27. Lowering PCSK9 with siPCSK9
28. ORION-11: Study design Eighteen months treatment and observation
29. ORION-11: Efficacy Durable, potent and consistent effect over 18 months
30. ORION-11: Efficacy Durable, potent and consistent effect over 18 months
31. ORION-11: Efficacy Potent, consistent response to inclisiran
32. ORION Phase III pooled analysis: Efficacy
33. ORION-11: Safety and tolerability Adverse event profile similar to placebo
34. ORION-11: Safety and tolerability Injection site AEs localized, mostly mild and transient
35. ORION-11: Safety and tolerability No evidence of liver, kidney, muscle or platelet toxicity
36. ORION-11: Safety and tolerability No difference in serious adverse events
37. ORION-11: Exploratory endpoint Adverse cardiovascular events
38. ORION-11: Summary Twice-a-year inclisiran lowered LDL-C by ≥50% safely
39. ORION-11: Conclusions and implications Inclisiran is the first cholesterol lowering siRNA
40. ORION-17: Renal impairment study Dose adjustments unnecessary for impaired renal function
41. Opportunities and challenges for the futur
42. Inclisiran / Leqvio® Indications cliniques
43. Inclisiran clinical studies
44. The modern concept of lipid-lowering strategies to reduce cardiovascular diseases
45. The modern concept of lipid-lowering strategies to reduce cardiovascular diseases
46. Novel lipid lowering drugs: PCSK9 and beyond
47. Consultation “Lipides” aux HUG
48. CV Risk factors & lifestyle
49. Merci pour votre attention
RNA en cardiologie, Pr François Mach, 18.05.2021
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