- Center on Health Equity & Access
- Clinical
- Health Care Cost
- Health Care Delivery
- Insurance
- Policy
- Technology
- Value-Based Care
Treatment of Heart Failure With ARNI Therapy
Panelists discuss how ARNIs like sacubitril-valsartan provide superior outcomes compared with ACE inhibitors in HFrEF (20% reduction in cardiovascular events, 16% mortality reduction), with broad FDA approval across the ejection fraction spectrum and recent generic availability improving cost-effectiveness, though ACE inhibitors and ARBs remain viable second-line options when ARNI is not accessible.
EP: 1.Economic Burden of Heart Failure Care
EP: 2.Heart Failure Prevalence and Screening
EP: 3.Quality Metrics in Heart Failure
EP: 4.Heart Failure Stages and Impact of Delayed Diagnosis
EP: 5.Collaboration in Heart Failure Treatment
EP: 6.Guideline-Directed Medical Therapies in Heart Failure
EP: 7.β-Blockers for Treatment of Heart Failure
EP: 8.Role of Diuretics in Heart Failure Management
EP: 9.Treatment of Heart Failure With ARNI Therapy
EP: 10.SGLT2 Inhibitors for Treatment of Heart Failure
Angiotensin receptor-neprilysin inhibitors (ARNIs) represent a significant advancement in heart failure therapy, combining an angiotensin receptor blocker (ARB) with neprilysin inhibition to enhance endogenous vasodilatory peptide systems. The landmark PARADIGM-HF trial demonstrated superiority of sacubitril-valsartan over the previous gold standard angiotensin-converting enzyme (ACE) inhibitor enalapril in patients with chronic heart failure with reduced ejection fraction (HFrEF), achieving a 20% reduction in composite cardiovascular outcomes and 16% reduction in overall mortality—representing an improvement over active comparator therapy, not placebo.
The evidence base extends across the heart failure spectrum, though with varying strength. While HFrEF benefits are unequivocal, PARAGON-HF in heart failure with preserved ejection fraction showed mixed results with directional signals of benefit, particularly in patients with ejection fractions below normal ranges. The FDA granted broad approval across the ejection fraction spectrum, with guidelines providing stronger recommendations for reduced ejection fraction and weaker recommendations for preserved ejection fraction populations.
Practical considerations include patient selection and economic factors. ARNIs are considered first-line therapy for HFrEF, with ACE inhibitors or ARBs serving as acceptable alternatives when ARNIs are not accessible due to cost or tolerability issues. Priority should be given to female patients with preserved ejection fraction (recognizing normal ejection fraction is slightly higher in women) and patients with recurrent hospitalizations. The recent availability of generic sacubitril-valsartan formulations may improve accessibility, potentially addressing cost barriers that previously limited optimal therapy implementation.
What It Takes to Improve Guideline-Based Heart Failure Care With Ty J. Gluckman, MD
August 5th 2025Explore innovative strategies to enhance heart failure treatment through guideline-directed medical therapy, remote monitoring, and artificial intelligence–driven solutions for better patient outcomes.
Listen
