{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T20:27:41Z","timestamp":1780864061364,"version":"3.54.1"},"reference-count":23,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2023,11,1]]},"abstract":"Importance<\/jats:title>The US Food and Drug Administration expanded labeling of sacubitril-valsartan from the treatment of patients with chronic heart failure (HF) with reduced ejection fraction (EF) to all patients with HF, noting the greatest benefits in those with below-normal EF. However, the upper bound of below normal is not clearly defined, and value determinations across a broader EF range are unknown.<\/jats:p><\/jats:sec>Objective<\/jats:title>To estimate the cost-effectiveness of sacubitril-valsartan vs renin-angiotensin system inhibitors (RASis) across various upper-level cutoffs of EF.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This economic evaluation included participant-level data from the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and the PARAGON-HF (Prospective Comparison of ARNi with ARB Global Outcomes in HF With Preserved Ejection Fraction) trials. PARADIGM-HF was conducted between 2009 and 2014, PARAGON-HF was conducted between 2014 and 2019, and this analysis was conducted between 2021 and 2023.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>A 5-state Markov model used risk reductions for all-cause mortality and HF hospitalization from PARADIGM-HF and PARAGON-HF. Quality-of-life differences were estimated from EuroQol-5D scores. Hospitalization and medication costs were obtained from published national sources; the wholesale acquisition cost of sacubitril-valsartan was $7092 per year. Risk estimates and treatment effects were generated in consecutive 5% EF increments up to 60% and applied to an EF distribution of US patients with HF from the Get With the Guidelines\u2013Heart Failure registry. The base case included a lifetime horizon from a health care sector perspective. Incremental cost-effectiveness ratios (ICERs) were estimated at EFs of 60% or less (base case) and at various upper-level EF cutoffs.<\/jats:p><\/jats:sec>Results<\/jats:title>Among 13 264 total patients whose data were analyzed, for those with EFs of 60% or less, sacubitril-valsartan was projected to add 0.53 quality-adjusted life-years (QALYs) at an incremental lifetime cost of $40\u202f892 compared with RASi, yielding an ICER of $76\u202f852 per QALY. In a probabilistic sensitivity analysis, 95% of the values of the ICER occurred between $71\u202f516 and $82\u202f970 per QALY. Among patients with chronic HF and an EF of 60% or less, treatment with sacubitril-valsartan vs RASis would be at least of economic intermediate value (ICER &amp;lt;$180\u202f000 per QALY) at a sacubitril-valsartan cost of $10\u202f242 or less per year, of high economic value (ICER &amp;lt;$60\u202f000 per QALY) at a cost of $3673 or less per year, and cost-saving at a cost of $338 or less per year. The ICERs were $67\u202f331 per QALY, $59\u202f614 per QALY, and $56\u202f786 per QALY at EFs of 55% or less, 50% or less, and 45% or less, respectively. Treatment with sacubitril-valsartan in only those with EFs of 45% or greater (up to \u226460%) yielded an ICER of $127\u202f172 per QALY gained; treatment was more cost-effective in those at the lower end of this range (ICER of $100\u202f388 per QALY gained for those with EFs of 45%-55%; ICER of $84\u202f291 per QALY gained for those with EFs of 45%-50%).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>Cost-effectiveness modeling provided an ICER for treatment with sacubitril-valsartan vs RASis consistent with high economic value for patients with reduced and mildly reduced EFs (\u226450%) and at least intermediate value at the current undiscounted wholesale acquisition cost price at an EF of 60% or less. Treatment was more cost-effective at lower EF ranges. These findings may have implications for coverage decisions and value assessments in contemporary clinical practice guidelines.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamacardio.2023.3216","type":"journal-article","created":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T15:33:40Z","timestamp":1695828820000},"page":"1041","source":"Crossref","is-referenced-by-count":18,"title":["Health and Economic Evaluation of Sacubitril-Valsartan for Heart Failure Management"],"prefix":"10.1001","volume":"8","author":[{"given":"Ankeet S.","family":"Bhatt","sequence":"first","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"},{"name":"Kaiser Permanente San Francisco Medical Center and Division of Research, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muthiah","family":"Vaduganathan","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Claggett","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregg C.","family":"Fonarow","sequence":"additional","affiliation":[{"name":"Ahmanson-UCLA Cardiomyopathy Center, University of California, Los Angeles"},{"name":"Associate Section Editor, JAMA Cardiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milton","family":"Packer","sequence":"additional","affiliation":[{"name":"Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc A.","family":"Pfeffer","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjiv J.","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Shen","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation, East Hanover, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquim","family":"Cristino","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation, East Hanover, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J. 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