{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:37:06Z","timestamp":1791247026305,"version":"4.1.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Cardiovascular Quality and Outcomes"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The 2022 clinical guidelines for management of heart failure with reduced ejection fraction call for quadruple therapy. Quadruple therapy consists of an angiotensin receptor-neprilysin inhibitor (ARNi), sodium-glucose cotransporter-2 inhibitor (SGLT2i), mineralocorticoid receptor antagonist, and beta blocker. The ARNi and sodium-glucose cotransporter-2 inhibitor are newer additions to standard of care with the ARNi replacing ACE (angiotensin-converting enzyme) inhibitors and angiotensin II receptor blockers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We investigate the cost-effectiveness of sequentially adding the SGLT2i and ARNi to form quadruple therapy as compared with the previous standard of care with ACE inhibitor\/mineralocorticoid receptor antagonist\/beta blocker. Using a 2-stage Markov model, we projected the expected lifetime discounted costs and quality-adjusted life years (QALYs) of a simulated cohort of US patients who underwent each treatment option and calculated incremental cost-effectiveness ratios. We assessed incremental cost-effectiveness ratios using criteria for health care value (&lt;$50\u2009000\/quality-adjusted life year [QALY] indicating high-value, $50\u2009000\u2013150\u2009000\/QALY indicating intermediate value, and &gt;$150\u2009000\/QALY indicating low-value) and a standard $100\u2009000\/QALY cost-effectiveness threshold.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Compared with the previous standard of care, the SGLT2i addition had an incremental cost-effectiveness ratio of $73\u2009000\/QALY and weakly dominated the ARNi addition. The addition of both the ARNi and SGLT2i for quadruple therapy offered 0.68 additional discounted QALYs over the SGLT2i addition alone at a lifetime discounted cost of $66\u2009700, resulting in an incremental cost-effectiveness ratio of $98\u2009500\/QALY. In sensitivity analysis varying drug prices, the incremental cost-effectiveness ratio for quadruple therapy ranged from $73\u2009500\/QALY using prices available to the US Department of Veterans Affairs to $110\u2009000\/QALY using drug list prices.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>While quadruple therapy offers intermediate value, it is borderline cost effective compared with adding the SGLT2i alone to previous standard of care. Thus, its cost-effectiveness is sensitive to a payer\u2019s ability to negotiate discounts off the increasing list prices for ARNI and SGLT2is. The demonstrated benefits of ARNi and SGLT2is should be weighed against their high prices in payer and policy considerations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circoutcomes.122.009793","type":"journal-article","created":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T14:23:56Z","timestamp":1686061436000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Cost-Effectiveness of Quadruple Therapy in Management of Heart Failure With Reduced Ejection Fraction in the United States"],"prefix":"10.1161","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0286-5764","authenticated-orcid":true,"given":"Brandon W.","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Health Policy and Management (B.W.Y., A.P.), Harvard T. H. Chan School of Public Health, Boston, MA."},{"name":"School of Medicine, University of California San Francisco (B.W.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9157-5648","authenticated-orcid":true,"given":"Aferdita","family":"Spahillari","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston (A.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6130-2286","authenticated-orcid":true,"given":"Ankur","family":"Pandya","sequence":"additional","affiliation":[{"name":"Department of Health Policy and Management (B.W.Y., A.P.), Harvard T. H. Chan School of Public Health, Boston, MA."},{"name":"Center for Health Decision Science (A.P.), Harvard T. H. 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