This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure

Summary

The study will evaluate the efficacy and safety of LCZ696 compared to enalapril on morbidity and mortality in patients with chronic heart failure (NYHA Class II - IV and EF =\< 35%).

Timeline

Start

2009-12

Primary completion

2014-05

Completion

2014-05

Outcome

Met primary endpoint

Stopped: “Early termination was approved due to compelling efficacy of LCZ696 in patients with HF \& reduced EF after final pre-specified interim analysis 28-Mar-2014.”

paper LCZ696 was superior to enalapril in reducing the risks of death and of hospitalization for heart failure. PMID 25176015 ↗

paper hazard ratio in the LCZ696 group, 0.80; 95% confidence interval [CI], 0.73 to 0.87; P<0.001 PMID 25176015 ↗

release “Overall there was a 20% risk reduction on the primary endpoint, a composite measure of CV death or time to first heart failure hospitalization.” novartis.com ↗

release “New analyses from the PARADIGM-HF trial showed Entresto (sacubitril/valsartan) reduces cardiovascular death and heart failure hospitalizations by 20% compared to ACE inhibitor enalapril” novartis.com ↗

release “These findings are consistent with the benefit Entresto showed in reducing the risk of a first event, which was the primary endpoint of the PARADIGM-HF” novartis.com ↗

release “Primary data from PARADIGM-HF, the largest clinical trial ever conducted in heart failure, showed that treatment with Entresto reduced the risk” novartis.com ↗

Publications

• Yang M, Henderson AD, Anand IS, Desai AS, Lam CSP, Maggioni AP, Martinez FA, Rouleau JL, Swedberg K, Vaduganathan M, van Veldhuisen DJ, Zannad F, Zile MR, Packer M, Rizkala A, Lewis EF, Jhund PS, Solomon SD, McMurray JJV. Sacubitril/valsartan and quality of life assessed using the EuroQol Five-dimension Three-level questionnaire level sum score (EQ-5D-3L-LSS) in patients with HFrEF and HFmrEF/HFpEF. Eur Heart J Cardiovasc Pharmacother. 2025 Nov 4;11(7):574-589. doi: 10.1093/ehjcvp/pvaf064.
• Chimura M, Butt JH, Matsumoto S, McMurray EGM, Henderson AD, Talebi A, Desai AS, Lefkowitz MP, Rizkala AR, Rouleau JL, Solomon SD, Swedberg K, Zile MR, Packer M, Jhund PS, McMurray JJV. Comprehensive Analysis of the Effects of Sacubitril/Valsartan According to Sex Among Patients With Heart Failure and Reduced Ejection Fraction in PARADIGM-HF. J Am Heart Assoc. 2025 May 6;14(9):e038249. doi: 10.1161/JAHA.124.038249. Epub 2025 Apr 23.
• Gupta SD, Butt JH, McMurray EGM, Talebi A, Matsumoto S, Rizkala AR, Henderson AD, Desai AS, Lefkowitz M, Packer M, Rouleau JL, Solomon SD, Swedberg K, Zile MR, Jhund PS, McMurray JJV; PARADIGM-HF Investigators and Committees. Effects of sacubitril/valsartan according to background beta-blocker therapy in patients with heart failure and reduced ejection fraction: Insights from PARADIGM-HF. Eur J Heart Fail. 2025 May;27(5):779-787. doi: 10.1002/ejhf.3515. Epub 2024 Nov 19.
• Lu H, Claggett BL, Packer M, Pfeffer MA, Swedberg K, Rouleau J, Zile MR, Lefkowitz M, Desai AS, Jhund PS, McMurray JJV, Solomon SD, Vaduganathan M. Visit-to-visit changes in heart rate in heart failure: A pooled participant-level analysis of the PARADIGM-HF and PARAGON-HF trials. Eur J Heart Fail. 2025 Jan;27(1):60-68. doi: 10.1002/ejhf.3487. Epub 2024 Oct 22.
• Lu H, Claggett BL, Packer M, Lam CSP, Swedberg K, Rouleau J, Zile MR, Lefkowitz M, Desai AS, Jhund P, McMurray JJV, Solomon SD, Vaduganathan M. Effects of Sacubitril/Valsartan on All-Cause Hospitalizations in Heart Failure: Post Hoc Analysis of the PARADIGM-HF and PARAGON-HF Randomized Clinical Trials. JAMA Cardiol. 2024 Nov 1;9(11):1047-1052. doi: 10.1001/jamacardio.2024.2566.
• Patel-Murray NL, Zhang L, Claggett BL, Xu D, Serrano-Fernandez P, Healey M, Wandel S, Chen CW, Jacob J, Xu H, Turner GM, Chutkow W, Yates DP, O'Donnell CJ, Prescott MF, Lefkowitz M, Gimpelewicz CR, Beste MT, Zhao F, Gou L, Desai AS, Jhund PS, Packer M, Pfeffer MA, Redfield MM, Rouleau JL, Zannad F, Zile MR, McMurray JJV, Mendelson MM, Solomon SD, Cunningham JW. Aptamer Proteomics for Biomarker Discovery in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Proteomic Substudy. J Am Heart Assoc. 2024 Jul 2;13(13):e033544. doi: 10.1161/JAHA.123.033544. Epub 2024 Jun 21.
• Chatur S, Neuen BL, Claggett BL, Beldhuis IE, Mc Causland FR, Desai AS, Rouleau JL, Zile MR, Lefkowitz MP, Packer M, McMurray JJV, Solomon SD, Vaduganathan M. Effects of Sacubitril/Valsartan Across the Spectrum of Renal Impairment in Patients With Heart Failure. J Am Coll Cardiol. 2024 Jun 4;83(22):2148-2159. doi: 10.1016/j.jacc.2024.03.392. Epub 2024 Apr 6.
• Bhatt AS, Vaduganathan M, Claggett BL, Kulac IJ, Anand IS, Desai AS, Fang JC, Hernandez AF, Jhund PS, Kosiborod MN, Sabatine MS, Shah SJ, Vardeny O, McMurray JJV, Solomon SD, Gaziano TA. Cost Effectiveness of Dapagliflozin for Heart Failure Across the Spectrum of Ejection Fraction: An Economic Evaluation Based on Pooled, Individual Participant Data From the DELIVER and DAPA-HF Trials. J Am Heart Assoc. 2024 Mar 5;13(5):e032279. doi: 10.1161/JAHA.123.032279. Epub 2024 Feb 23.
• Curtain JP, Adamson C, Docherty KF, Jhund PS, Desai AS, Lefkowitz MP, Rizkala AR, Rouleau JL, Swedberg K, Zile MR, Solomon SD, Packer M, McMurray JJV. Prevalent and Incident Anemia in PARADIGM-HF and the Effect of Sacubitril/Valsartan. JACC Heart Fail. 2023 Jul;11(7):749-759. doi: 10.1016/j.jchf.2022.12.012. Epub 2023 Apr 12.
• Kondo T, Dewan P, Anand IS, Desai AS, Packer M, Zile MR, Pfeffer MA, Solomon SD, Abraham WT, Shah SJ, Lam CSP, Jhund PS, McMurray JJV. Clinical Characteristics and Outcomes in Patients With Heart Failure: Are There Thresholds and Inflection Points in Left Ventricular Ejection Fraction and Thresholds Justifying a Clinical Classification? Circulation. 2023 Aug 29;148(9):732-749. doi: 10.1161/CIRCULATIONAHA.122.063642. Epub 2023 Jun 27.
• Tolomeo P, Butt JH, Kondo T, Campo G, Desai AS, Jhund PS, Kober L, Lefkowitz MP, Rouleau JL, Solomon SD, Swedberg K, Vaduganathan M, Zile MR, Packer M, McMurray JJV. Importance of cystatin C in estimating glomerular filtration rate: the PARADIGM-HF trial. Eur Heart J. 2023 Jun 25;44(24):2202-2212. doi: 10.1093/eurheartj/ehad210.
• Butt JH, Ibrahim W, Dewan P, Desai AS, Kober L, Prescott MF, Lefkowitz MP, Rouleau JL, Solomon SD, Zile MR, Packer M, Jhund PS, McMurray JJV. Urinary cGMP (Cyclic Guanosine Monophosphate)/BNP (B-Type Natriuretic Peptide) Ratio, Sacubitril/Valsartan, and Outcomes in Heart Failure With Reduced Ejection Fraction: An Analysis of the PARADIGM-HF Trial. Circ Heart Fail. 2023 Mar;16(3):e010111. doi: 10.1161/CIRCHEARTFAILURE.122.010111. Epub 2023 Jan 25.
• Rohde LE, Zimerman A, Vaduganathan M, Claggett BL, Packer M, Desai AS, Zile M, Rouleau J, Swedberg K, Lefkowitz M, Shi V, McMurray JJV, Solomon SD. Associations Between New York Heart Association Classification, Objective Measures, and Long-term Prognosis in Mild Heart Failure: A Secondary Analysis of the PARADIGM-HF Trial. JAMA Cardiol. 2023 Feb 1;8(2):150-158. doi: 10.1001/jamacardio.2022.4427.
• Vaduganathan M, Claggett BL, McMurray JJV, Solomon SD. Health Status Trajectories Before and After Hospitalization for Heart Failure. Circulation. 2022 Jun 21;145(25):1872-1874. doi: 10.1161/CIRCULATIONAHA.122.059282. Epub 2022 May 21. No abstract available.
• Toenges G, Mutze T, Jahn-Eimermacher A. A comparison of semiparametric approaches to evaluate composite endpoints in heart failure trials. Stat Med. 2021 Nov 20;40(26):5702-5724. doi: 10.1002/sim.9149. Epub 2021 Jul 30.
• Shen L, Claggett BL, Jhund PS, Abraham WT, Desai AS, Dickstein K, Gong J, Kober LV, Lefkowitz MP, Rouleau JL, Shi VC, Swedberg K, Zile MR, Solomon SD, McMurray JJV. Development and external validation of prognostic models to predict sudden and pump-failure death in patients with HFrEF from PARADIGM-HF and ATMOSPHERE. Clin Res Cardiol. 2021 Aug;110(8):1334-1349. doi: 10.1007/s00392-021-01888-x. Epub 2021 Jun 8.
• Shen L, Jhund PS, Anand IS, Bhatt AS, Desai AS, Maggioni AP, Martinez FA, Pfeffer MA, Rizkala AR, Rouleau JL, Swedberg K, Vaduganathan M, Vardeny O, van Veldhuisen DJ, Zannad F, Zile MR, Packer M, Solomon SD, McMurray JJV. Incidence and Outcomes of Pneumonia in Patients With Heart Failure. J Am Coll Cardiol. 2021 Apr 27;77(16):1961-1973. doi: 10.1016/j.jacc.2021.03.001.
• Ehteshami-Afshar S, Mooney L, Dewan P, Desai AS, Lang NN, Lefkowitz MP, Petrie MC, Rizkala AR, Rouleau JL, Solomon SD, Swedberg K, Shi VC, Zile MR, Packer M, McMurray JJV, Jhund PS, Hawkins NM. Clinical Characteristics and Outcomes of Patients With Heart Failure With Reduced Ejection Fraction and Chronic Obstructive Pulmonary Disease: Insights From PARADIGM-HF. J Am Heart Assoc. 2021 Feb 16;10(4):e019238. doi: 10.1161/JAHA.120.019238. Epub 2021 Jan 30.
• Kristensen SL, Castagno D, Shen L, Jhund PS, Docherty KF, Rorth R, Abraham WT, Desai AS, Dickstein K, Rouleau JL, Zile MR, Swedberg K, Packer M, Solomon SD, Kober L, McMurray JJV; PARADIGM-HF and ATMOSPHERE Committees and Investigators.. Prevalence and incidence of intra-ventricular conduction delays and outcomes in patients with heart failure and reduced ejection fraction: insights from PARADIGM-HF and ATMOSPHERE. Eur J Heart Fail. 2020 Dec;22(12):2370-2379. doi: 10.1002/ejhf.1972. Epub 2020 Sep 14.
• Docherty KF, Shen L, Castagno D, Petrie MC, Abraham WT, Bohm M, Desai AS, Dickstein K, Kober LV, Packer M, Rouleau JL, Solomon SD, Swedberg K, Vazir A, Zile MR, Jhund PS, McMurray JJV. Relationship between heart rate and outcomes in patients in sinus rhythm or atrial fibrillation with heart failure and reduced ejection fraction. Eur J Heart Fail. 2020 Mar;22(3):528-538. doi: 10.1002/ejhf.1682. Epub 2019 Dec 17.
• Dewan P, Rorth R, Raparelli V, Campbell RT, Shen L, Jhund PS, Petrie MC, Anand IS, Carson PE, Desai AS, Granger CB, Kober L, Komajda M, McKelvie RS, O'Meara E, Pfeffer MA, Pitt B, Solomon SD, Swedberg K, Zile MR, McMurray JJV. Sex-Related Differences in Heart Failure With Preserved Ejection Fraction. Circ Heart Fail. 2019 Dec;12(12):e006539. doi: 10.1161/CIRCHEARTFAILURE.119.006539. Epub 2019 Dec 9.
• Solomon SD, Vaduganathan M, L Claggett B, Packer M, Zile M, Swedberg K, Rouleau J, A Pfeffer M, Desai A, Lund LH, Kober L, Anand I, Sweitzer N, Linssen G, Merkely B, Luis Arango J, Vinereanu D, Chen CH, Senni M, Sibulo A, Boytsov S, Shi V, Rizkala A, Lefkowitz M, McMurray JJV. Sacubitril/Valsartan Across the Spectrum of Ejection Fraction in Heart Failure. Circulation. 2020 Feb 4;141(5):352-361. doi: 10.1161/CIRCULATIONAHA.119.044586. Epub 2019 Nov 17.
• Selvaraj S, Claggett B, Pozzi A, McMurray JJV, Jhund PS, Packer M, Desai AS, Lewis EF, Vaduganathan M, Lefkowitz MP, Rouleau JL, Shi VC, Zile MR, Swedberg K, Solomon SD. Prognostic Implications of Congestion on Physical Examination Among Contemporary Patients With Heart Failure and Reduced Ejection Fraction: PARADIGM-HF. Circulation. 2019 Oct 22;140(17):1369-1379. doi: 10.1161/CIRCULATIONAHA.119.039920. Epub 2019 Sep 12.
• Chandra A, Vaduganathan M, Lewis EF, Claggett BL, Rizkala AR, Wang W, Lefkowitz MP, Shi VC, Anand IS, Ge J, Lam CSP, Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B, Redfield MM, Rouleau JL, Van Veldhuisen DJ, Zannad F, Zile MR, McMurray JJV, Solomon SD; PARAGON-HF Investigators. Health-Related Quality of Life in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Trial. JACC Heart Fail. 2019 Oct;7(10):862-874. doi: 10.1016/j.jchf.2019.05.015. Epub 2019 Jul 10.
• Balmforth C, Simpson J, Shen L, Jhund PS, Lefkowitz M, Rizkala AR, Rouleau JL, Shi V, Solomon SD, Swedberg K, Zile MR, Packer M, McMurray JJV. Outcomes and Effect of Treatment According to Etiology in HFrEF: An Analysis of PARADIGM-HF. JACC Heart Fail. 2019 Jun;7(6):457-465. doi: 10.1016/j.jchf.2019.02.015. Epub 2019 May 8.
• Myhre PL, Vaduganathan M, Claggett B, Packer M, Desai AS, Rouleau JL, Zile MR, Swedberg K, Lefkowitz M, Shi V, McMurray JJV, Solomon SD. B-Type Natriuretic Peptide During Treatment With Sacubitril/Valsartan: The PARADIGM-HF Trial. J Am Coll Cardiol. 2019 Mar 26;73(11):1264-1272. doi: 10.1016/j.jacc.2019.01.018. Epub 2019 Mar 4.
• Zile MR, O'Meara E, Claggett B, Prescott MF, Solomon SD, Swedberg K, Packer M, McMurray JJV, Shi V, Lefkowitz M, Rouleau J. Effects of Sacubitril/Valsartan on Biomarkers of Extracellular Matrix Regulation in Patients With HFrEF. J Am Coll Cardiol. 2019 Feb 26;73(7):795-806. doi: 10.1016/j.jacc.2018.11.042.
• Bouabdallaoui N, Claggett B, Zile MR, McMurray JJV, O'Meara E, Packer M, Prescott MF, Swedberg K, Solomon SD, Rouleau JL; PARADIGM-HF Investigators and Committees. Growth differentiation factor-15 is not modified by sacubitril/valsartan and is an independent marker of risk in patients with heart failure and reduced ejection fraction: the PARADIGM-HF trial. Eur J Heart Fail. 2018 Dec;20(12):1701-1709. doi: 10.1002/ejhf.1301. Epub 2018 Sep 11.
• O'Meara E, Prescott MF, Claggett B, Rouleau JL, Chiang LM, Solomon SD, Packer M, McMurray JJV, Zile MR. Independent Prognostic Value of Serum Soluble ST2 Measurements in Patients With Heart Failure and a Reduced Ejection Fraction in the PARADIGM-HF Trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure). Circ Heart Fail. 2018 May;11(5):e004446. doi: 10.1161/CIRCHEARTFAILURE.117.004446.
• Packer M, Claggett B, Lefkowitz MP, McMurray JJV, Rouleau JL, Solomon SD, Zile MR. Effect of neprilysin inhibition on renal function in patients with type 2 diabetes and chronic heart failure who are receiving target doses of inhibitors of the renin-angiotensin system: a secondary analysis of the PARADIGM-HF trial. Lancet Diabetes Endocrinol. 2018 Jul;6(7):547-554. doi: 10.1016/S2213-8587(18)30100-1. Epub 2018 Apr 13.
• Chandra A, Lewis EF, Claggett BL, Desai AS, Packer M, Zile MR, Swedberg K, Rouleau JL, Shi VC, Lefkowitz MP, Katova T, McMurray JJV, Solomon SD. Effects of Sacubitril/Valsartan on Physical and Social Activity Limitations in Patients With Heart Failure: A Secondary Analysis of the PARADIGM-HF Trial. JAMA Cardiol. 2018 Jun 1;3(6):498-505. doi: 10.1001/jamacardio.2018.0398.
• Shen L, Ramires F, Martinez F, Bodanese LC, Echeverria LE, Gomez EA, Abraham WT, Dickstein K, Kober L, Packer M, Rouleau JL, Solomon SD, Swedberg K, Zile MR, Jhund PS, Gimpelewicz CR, McMurray JJV; PARADIGM-HF and ATMOSPHERE Investigators and Committees. Contemporary Characteristics and Outcomes in Chagasic Heart Failure Compared With Other Nonischemic and Ischemic Cardiomyopathy. Circ Heart Fail. 2017 Nov;10(11):e004361. doi: 10.1161/CIRCHEARTFAILURE.117.004361.
• Kristensen SL, Jhund PS, Mogensen UM, Rorth R, Abraham WT, Desai A, Dickstein K, Rouleau JL, Zile MR, Swedberg K, Packer M, Solomon SD, Kober L, McMurray JJV; PARADIGM-HF and ATMOSPHERE Committees and Investigators. Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide Levels in Heart Failure Patients With and Without Atrial Fibrillation. Circ Heart Fail. 2017 Oct;10(10):e004409. doi: 10.1161/CIRCHEARTFAILURE.117.004409.
• Lewis EF, Claggett BL, McMurray JJV, Packer M, Lefkowitz MP, Rouleau JL, Liu J, Shi VC, Zile MR, Desai AS, Solomon SD, Swedberg K. Health-Related Quality of Life Outcomes in PARADIGM-HF. Circ Heart Fail. 2017 Aug;10(8):e003430. doi: 10.1161/CIRCHEARTFAILURE.116.003430.
• Zile MR, Claggett BL, Prescott MF, McMurray JJ, Packer M, Rouleau JL, Swedberg K, Desai AS, Gong J, Shi VC, Solomon SD. Prognostic Implications of Changes in N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Heart Failure. J Am Coll Cardiol. 2016 Dec 6;68(22):2425-2436. doi: 10.1016/j.jacc.2016.09.931.
• Nadruz W Jr, Claggett BL, McMurray JJ, Packer M, Zile MR, Rouleau JL, Desai AS, Swedberg K, Lefkowitz M, Shi VC, Prescott MF, Solomon SD. Impact of Body Mass Index on the Accuracy of N-Terminal Pro-Brain Natriuretic Peptide and Brain Natriuretic Peptide for Predicting Outcomes in Patients With Chronic Heart Failure and Reduced Ejection Fraction: Insights From the PARADIGM-HF Study (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial). Circulation. 2016 Nov 29;134(22):1785-1787. doi: 10.1161/CIRCULATIONAHA.116.024976. No abstract available.
• Desai AS, Vardeny O, Claggett B, McMurray JJ, Packer M, Swedberg K, Rouleau JL, Zile MR, Lefkowitz M, Shi V, Solomon SD. Reduced Risk of Hyperkalemia During Treatment of Heart Failure With Mineralocorticoid Receptor Antagonists by Use of Sacubitril/Valsartan Compared With Enalapril: A Secondary Analysis of the PARADIGM-HF Trial. JAMA Cardiol. 2017 Jan 1;2(1):79-85. doi: 10.1001/jamacardio.2016.4733.
• Okumura N, Jhund PS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Swedberg K, Zile MR, Solomon SD, Packer M, McMurray JJ; PARADIGM-HF Investigators and Committees*. Effects of Sacubitril/Valsartan in the PARADIGM-HF Trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) According to Background Therapy. Circ Heart Fail. 2016 Sep;9(9):e003212. doi: 10.1161/CIRCHEARTFAILURE.116.003212.
• Solomon SD, Claggett B, Packer M, Desai A, Zile MR, Swedberg K, Rouleau J, Shi V, Lefkowitz M, McMurray JJV. Efficacy of Sacubitril/Valsartan Relative to a Prior Decompensation: The PARADIGM-HF Trial. JACC Heart Fail. 2016 Oct;4(10):816-822. doi: 10.1016/j.jchf.2016.05.002. Epub 2016 Jul 6.
• Kristensen SL, Martinez F, Jhund PS, Arango JL, Belohlavek J, Boytsov S, Cabrera W, Gomez E, Hagege AA, Huang J, Kiatchoosakun S, Kim KS, Mendoza I, Senni M, Squire IB, Vinereanu D, Wong RC, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR, Packer M, McMurray JJ. Geographic variations in the PARADIGM-HF heart failure trial. Eur Heart J. 2016 Nov 1;37(41):3167-3174. doi: 10.1093/eurheartj/ehw226. Epub 2016 Jun 28.
• Desai AS, Solomon S, Claggett B, McMurray JJ, Rouleau J, Swedberg K, Zile M, Lefkowitz M, Shi V, Packer M. Factors Associated With Noncompletion During the Run-In Period Before Randomization and Influence on the Estimated Benefit of LCZ696 in the PARADIGM-HF Trial. Circ Heart Fail. 2016 Jun;9(6):e002735. doi: 10.1161/CIRCHEARTFAILURE.115.002735.
• Okumura N, Jhund PS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Swedberg K, Zile MR, Solomon SD, Packer M, McMurray JJ; PARADIGM-HF Investigators and Committees*. Importance of Clinical Worsening of Heart Failure Treated in the Outpatient Setting: Evidence From the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial (PARADIGM-HF). Circulation. 2016 Jun 7;133(23):2254-62. doi: 10.1161/CIRCULATIONAHA.115.020729. Epub 2016 Apr 20.
• Solomon SD, Claggett B, Desai AS, Packer M, Zile M, Swedberg K, Rouleau JL, Shi VC, Starling RC, Kozan O, Dukat A, Lefkowitz MP, McMurray JJ. Influence of Ejection Fraction on Outcomes and Efficacy of Sacubitril/Valsartan (LCZ696) in Heart Failure with Reduced Ejection Fraction: The Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) Trial. Circ Heart Fail. 2016 Mar;9(3):e002744. doi: 10.1161/CIRCHEARTFAILURE.115.002744.
• Kristensen SL, Preiss D, Jhund PS, Squire I, Cardoso JS, Merkely B, Martinez F, Starling RC, Desai AS, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR, McMurray JJ, Packer M; PARADIGM-HF Investigators and Committees. Risk Related to Pre-Diabetes Mellitus and Diabetes Mellitus in Heart Failure With Reduced Ejection Fraction: Insights From Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial. Circ Heart Fail. 2016 Jan;9(1):e002560. doi: 10.1161/CIRCHEARTFAILURE.115.002560.
• Simpson J, Jhund PS, Silva Cardoso J, Martinez F, Mosterd A, Ramires F, Rizkala AR, Senni M, Squire I, Gong J, Lefkowitz MP, Shi VC, Desai AS, Rouleau JL, Swedberg K, Zile MR, McMurray JJV, Packer M, Solomon SD; PARADIGM-HF Investigators and Committees. Comparing LCZ696 with enalapril according to baseline risk using the MAGGIC and EMPHASIS-HF risk scores: an analysis of mortality and morbidity in PARADIGM-HF. J Am Coll Cardiol. 2015 Nov 10;66(19):2059-2071. doi: 10.1016/j.jacc.2015.08.878.
• Andersen MB, Simonsen U, Wehland M, Pietsch J, Grimm D. LCZ696 (Valsartan/Sacubitril)--A Possible New Treatment for Hypertension and Heart Failure. Basic Clin Pharmacol Toxicol. 2016 Jan;118(1):14-22. doi: 10.1111/bcpt.12453. Epub 2015 Sep 4.
• Jhund PS, Fu M, Bayram E, Chen CH, Negrusz-Kawecka M, Rosenthal A, Desai AS, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR, McMurray JJ, Packer M; PARADIGM-HF Investigators and Committees. Efficacy and safety of LCZ696 (sacubitril-valsartan) according to age: insights from PARADIGM-HF. Eur Heart J. 2015 Oct 7;36(38):2576-84. doi: 10.1093/eurheartj/ehv330. Epub 2015 Jul 31.
• Desai AS, McMurray JJ, Packer M, Swedberg K, Rouleau JL, Chen F, Gong J, Rizkala AR, Brahimi A, Claggett B, Finn PV, Hartley LH, Liu J, Lefkowitz M, Shi V, Zile MR, Solomon SD. Effect of the angiotensin-receptor-neprilysin inhibitor LCZ696 compared with enalapril on mode of death in heart failure patients. Eur Heart J. 2015 Aug 7;36(30):1990-7. doi: 10.1093/eurheartj/ehv186. Epub 2015 May 28.
• McMurray J, Packer M, Desai A, Gong J, Greenlaw N, Lefkowitz M, Rizkala A, Shi V, Rouleau J, Solomon S, Swedberg K, Zile MR, Andersen K, Arango JL, Arnold M, Belohlavek J, Bohm M, Boytsov S, Burgess L, Cabrera W, Chen CH, Erglis A, Fu M, Gomez E, Gonzalez A, Hagege AA, Katova T, Kiatchoosakun S, Kim KS, Bayram E, Martinez F, Merkely B, Mendoza I, Mosterd A, Negrusz-Kawecka M, Peuhkurinen K, Ramires F, Refsgaard J, Senni M, Sibulo AS Jr, Silva-Cardoso J, Squire I, Starling RC, Vinereanu D, Teerlink JR, Wong R; PARADIGM-HF Committees and Investigators. A putative placebo analysis of the effects of LCZ696 on clinical outcomes in heart failure. Eur Heart J. 2015 Feb 14;36(7):434-9. doi: 10.1093/eurheartj/ehu455.
• Packer M, McMurray JJ, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile M, Andersen K, Arango JL, Arnold JM, Belohlavek J, Bohm M, Boytsov S, Burgess LJ, Cabrera W, Calvo C, Chen CH, Dukat A, Duarte YC, Erglis A, Fu M, Gomez E, Gonzalez-Medina A, Hagege AA, Huang J, Katova T, Kiatchoosakun S, Kim KS, Kozan O, Llamas EB, Martinez F, Merkely B, Mendoza I, Mosterd A, Negrusz-Kawecka M, Peuhkurinen K, Ramires FJ, Refsgaard J, Rosenthal A, Senni M, Sibulo AS Jr, Silva-Cardoso J, Squire IB, Starling RC, Teerlink JR, Vanhaecke J, Vinereanu D, Wong RC; PARADIGM-HF Investigators and Coordinators. Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure. Circulation. 2015 Jan 6;131(1):54-61. doi: 10.1161/CIRCULATIONAHA.114.013748. Epub 2014 Nov 17.
• McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004. doi: 10.1056/NEJMoa1409077. Epub 2014 Aug 30.
• McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau J, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Committees and Investigators. Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF). Eur J Heart Fail. 2013 Sep;15(9):1062-73. doi: 10.1093/eurjhf/hft052. Epub 2013 Apr 5.

Drugs

Evaluation	Drug	Modality	Dose	Route
Comparator	Enalapril	Other / unclassified	10 mg	—
Subject	LCZ696	Unknown	200 mg	—

Indications