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The Basic Science of Heart Failure: Dual-Action Molecules in Perspective

The Basic Science of Heart Failure: Dual-Action Molecules in Perspective. Adverse Neurohormonal Activation in HF Has Formed the Basis for Evidence-Based Pharmacologic Therapy. Renin-Angiotensin-Aldosterone System. RAAS Inhibition in CHF.

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The Basic Science of Heart Failure: Dual-Action Molecules in Perspective

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  1. The Basic Science of Heart Failure: Dual-Action Molecules in Perspective

  2. Adverse Neurohormonal Activation in HF Has Formed the Basis for Evidence-Based Pharmacologic Therapy

  3. Renin-Angiotensin-Aldosterone System

  4. RAAS Inhibition in CHF

  5. Effect of ACE Inhibition in Patients With CHF: CONSENSUS Trial

  6. Effect of ACE Inhibition in Patients With CHF: SOLVD Trial

  7. ARBs: Another Way to Inhibit the RAS

  8. ARBs: No Better Than ACE Inhibitors But Probably AS GOOD AS

  9. ATMOSPHERE: Would Dual Blockade of the RAS With Evidence-Based Background Therapy Be Superior to Single-Agent RAS Inhibition?

  10. ATMOSPHERE: Direct Renin Inhibition and ACE Inhibition Similar: DUAL Inhibition NO BETTER and Produced More Side Effects

  11. Have we pushed inhibiting the RAAS as far as we could go?

  12. NP System: Endogenous Compensatory Mechanisms in HF Counteract Some Deleterious Effects of RAAS Activation

  13. Action and Clearance of NPs

  14. Sacubitril/Valsartan: ARNI—Simultaneously Inhibits RAS and Augments Vasoactive Peptides

  15. PARADIGM-HF: Study Design

  16. PARADIGM-HF Primary Results: Significant Reduction in Primary Endpoints, CV Death, andAll-Cause Mortality

  17. PARADIGM-HF: Sacubitril/Valsartan (LCZ696) vs Enalapril on Primary Endpoint and on CV Death, by Subgroups

  18. PARADIGM-HF: Early Benefit of Sacubitril/Valsartan

  19. PARADIGM-HF: Sacubitril/Valsartan Effective Across a Spectrum of Risk: The MAGGIC Risk Score

  20. The PARADIGM-HF Trial

  21. Influence of Sacubitril/Valsartan on 30-Day Readmission After HF Hospitalization

  22. Estimated Long-term Benefit of 1.5-2 Years Using Actuarial Methods: Based on PARADIGM-HF

  23. Potential Mortality Reduction With Optimal Implementation of ARNI Therapy in HF

  24. Sacubitril/Valsartan Was Effective Across the Spectrum of EF: PARADIGM-HF Enrolled >2000 Patients With EF Between 35% and 40%

  25. PARADIGM-HF: Baseline MRA (Aldosterone) Use

  26. PARADIGM-HF: Comparison of Sacubitril/Valsartan vs Enalapril in Dose-Reduced Patients

  27. NT-proBNP and BNP

  28. PARADIGM-HF: Measurement of NT-proBNP and BNP

  29. No Heterogeneity in Treatment Effect by NT-proBNP at Baseline

  30. PARADIGM-HF: Influence of Sacubitril/Valsartan on NT-proBNP Reduction and Influence on Outcomes

  31. ARNI Use in HF: Guideline Recommendations

  32. PARAMOUNT: Designed in Parallel With PARADIGM-HF to Provide Pilot Data for Sacubitril/Valsartan in HFpEF

  33. PARAMOUNT: Significant Reduction in NT-proBNP With Sacubitril/Valsartan at 12 Weeks

  34. PARAMOUNT: Improvement in Left Atrial Size and NYHA Class With Sacubitril/Valsartan at 36 Weeks

  35. PARAGON-HF: Trial Design

  36. PARADISE-MI: Trial Design

  37. Summary

  38. Abbreviations

  39. Abbreviations (cont)

  40. Abbreviations (cont)

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