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Published on: March 29, 2024
Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction
Scott D Solomon1, John J V McMurray1, Inder S Anand1
1From the Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston (S.D.S., M.A.P., A.S.D., B.C.); the British Heart Foundation Cardiovascular Research Centre (J.J.V.M., P.S.J.) and the Robertson Centre for Biostatistics and Clinical Trials, Institute of Health and Well-being (J.C.), University of Glasgow, Glasgow, and the National Heart and Lung Institute, Royal Brompton and Harefield Hospitals, Imperial College, London (J.C.) - all in the United Kingdom; University of Minnesota, Minneapolis (I.S.A), and Mayo Clinic, Rochester (M.M.R.) - both in Minnesota; Shanghai Institute of Cardiovascular Diseases (J. Ge) and the Department of Cardiology (J.Z.), Zhongshan Hospital, Fudan University, Shanghai, China; National Heart Center Singapore and Duke-National University of Singapore, Singapore (C.S.P.L); National Association of Hospital Cardiologists Research Center, Florence (A.P.M.), and the Cardiology Division, Cardiovascular Department, Hospital Papa Giovanni XXIII, Bergamo (M.S.) - both in Italy; National University of Cordoba, Cordoba, Argentina (F.M.); Baylor University Medical Center, Dallas (M.P.); the Department of Internal Medicine and Cardiology, German Center for Cardiovascular Research partner site Berlin (B.P.), and the Department of Cardiology, Charité Universitätsmedizin, Campus Virchow-Klinikum (H.-D.D.) - both in Berlin; Institut de Cardiologie de Montréal, Université de Montréal, Montreal (J.L.R.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (D.J.V.); INSERM Centre d'Investigation Clinic 1433 and Université de Lorraine, Centre Hospitalier Régional et Universitaire, Nancy, France (F.Z.); Medical University of South Carolina and the Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston (M.R.Z.); National Research Center for Cardiology of the Ministry of Health of the Russian Federation, Moscow (S.A.B.); Community Heart Failure Program, Department of Cardiology, Bellvitge University Hospital and Bellvitge Institute for Biomedical Research, University of Barcelona, Barcelona (J.C.-C.); Department of Heart Failure-Transplantation, National Cardiovascular Institute, Bratislava, Slovakia (E.G.); Clinic of Cardiology, National Cardiology Hospital, Sofia, Bulgaria (T.K.); Disciplina de Cardiologia Faculdade de Medicina Pontifícia Universidade Católica de Campinas, São Paulo (J.F.K.S.); the Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland (M.L.); Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (S.J.S); and Novartis Pharmaceuticals, East Hanover, NJ (A.R.R., J. Gong, V.C.S., M.P.L.).
Sacubitril-valsartan did not significantly reduce hospitalizations or cardiovascular death in patients with heart failure and preserved ejection fraction. However, it showed potential benefits in specific subgroups like women and those with lower ejection fractions.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Angiotensin receptor-neprilysin inhibitors (ARNI) like sacubitril-valsartan have shown efficacy in heart failure with reduced ejection fraction (HFrEF).
- The effectiveness of ARNIs in heart failure with preserved ejection fraction (HFpEF) remains unclear, necessitating further investigation.
Purpose of the Study:
- To evaluate the efficacy of sacubitril-valsartan compared to valsartan in patients with heart failure and preserved ejection fraction (HFpEF).
- To assess the primary outcome of composite hospitalizations for heart failure and cardiovascular death in this patient population.
Main Methods:
- A randomized trial involving 4822 patients with NYHA class II-IV HF, EF ≥45%, elevated natriuretic peptides, and structural heart disease.
- Patients received either sacubitril-valsartan or valsartan, with primary outcome assessment including total heart failure hospitalizations and cardiovascular death.
- Secondary outcomes included changes in NYHA class, renal function, Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, and safety assessments.
Main Results:
- The primary composite outcome occurred in 894 patients (sacubitril-valsartan) vs. 1009 patients (valsartan) (rate ratio, 0.87; P=0.06), not reaching statistical significance.
- Cardiovascular death incidence was 8.5% vs. 8.9%, and heart failure hospitalizations were 690 vs. 797, respectively.
- Improvements in NYHA class and KCCQ scores were observed with sacubitril-valsartan. Worsening renal function was lower, but hypotension and angioedema were higher. Heterogeneity suggested benefit in women and lower EF subgroups.
Conclusions:
- Sacubitril-valsartan did not achieve a statistically significant reduction in the primary composite outcome of heart failure hospitalizations or cardiovascular death in patients with HFpEF (EF ≥45%).
- Despite not meeting the primary endpoint, the study indicated potential benefits in specific patient subgroups and on certain secondary endpoints, warranting further research.
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