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

Effect of ACE Inhibition in Patients With CHF: CONSENSUS Trial

Effect of ACE Inhibition in Patients With CHF: SOLVD Trial

ARBs: Another Way to Inhibit the RAS

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

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

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

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

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

Action and Clearance of NPs

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

PARADIGM-HF: Study Design

PARADIGM-HF Primary Results: Significant Reduction in Primary Endpoints, CV Death, and All-Cause Mortality

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

PARADIGM-HF: Early Benefit of Sacubitril/Valsartan

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

The PARADIGM-HF Trial

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

Estimated Long-term Benefit of 1 Estimated Long-term Benefit of 1.5-2 Years Using Actuarial Methods: Based on PARADIGM-HF

Potential Mortality Reduction With Optimal Implementation of ARNI Therapy in HF

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

PARADIGM-HF: Baseline MRA (Aldosterone) Use

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

NT-proBNP and BNP

PARADIGM-HF: Measurement of NT-proBNP and BNP

No Heterogeneity in Treatment Effect by NT-proBNP at Baseline

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

ARNI Use in HF: Guideline Recommendations

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

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

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

PARAGON-HF: Trial Design

PARADISE-MI: Trial Design

Summary

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Abbreviations (cont)

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