{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T15:49:50Z","timestamp":1786549790489,"version":"build-2736575974"},"reference-count":13,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"\n Importance<\/jats:title>\n Contemporary guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF), which includes angiotensin receptor\u2013neprilysin inhibitors (ARNI), \u03b2-blockers, mineralocorticoid receptor antagonists (MRAs), and sodium\u2013glucose cotransporter 2 inhibitors (SGLT2i), reduces hospitalizations in randomized clinical trials (RCTs), but the combined economic impact of implementing full quadruple therapy after hospitalization is not well quantified.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To estimate the 1-year health care cost offset and net cost associated with implementation of quadruple GDMT after hospitalization for HFrEF.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This economic evaluation used Medicare-linked data from the American Heart Association\u2019s Get With The Guidelines\u2013Heart Failure (GWTG-HF) registry to identify adults 65 years or older hospitalized with HFrEF from 2016 to 2020 with up to 1-year postdischarge follow-up. Data were analyzed from November 2025 to February 2026.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Receipt of quadruple GDMT, defined as concurrent use of an ARNI, \u03b2-blocker, MRA, and SGLT2i, at hospital discharge and modeled according to class-specific eligibility and treatment effect estimates from pivotal RCTs.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Mean per-patient total health care costs through 1 year after discharge were calculated using Medicare Parts A and B payments. Treatment effect estimates for ARNI, \u03b2-blockers, MRAs, and SGLT2i were derived from pivotal RCTs and combined multiplicatively on the log scale, incorporating class-specific eligibility, to estimate projected reductions in hospitalization-associated expenditures. Net annual cost was calculated by integrating drug acquisition costs across multiple pricing sources with predicted hospitalization cost reductions.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n The cohort included 50\u202f598 older adults hospitalized with HFrEF (median [IQR] age, 78 [72-85] years; 31\u202f268 men [61.8%] and 19\u202f330 women [38.2%]). Mean 1-year total health care costs were $41\u202f802 per patient, with $25\u202f172 attributable to all-cause hospitalizations. Modeled quadruple GDMT was associated with an 87% (95% CI, 81%-91%) relative reduction in HF hospitalizations and a 61% (95% CI, 51%-68%) reduction in all-cause hospitalizations. Full quadruple therapy implementation vs partial GDMT was projected to reduce hospitalization-associated expenditures by $9780 (95% CI, $7900-$11\u202f660) per patient annually. With annual drug costs ranging from $1223 to $16\u202f136, the resulting net annual cost ranged from $8556 in savings to $6347 in net cost, with most regimens yielding net savings.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n Among US adults hospitalized with HFrEF, 1-year health care costs are substantial and driven predominantly by hospitalizations. Using combined trial effects and real-world Medicare data, this study found that implementation of quadruple GDMT would meaningfully reduce hospitalization-associated costs and often yield net savings after accounting for medication expenses.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamacardio.2026.1552","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:30:40Z","timestamp":1781105440000},"page":"767","source":"Crossref","is-referenced-by-count":0,"title":["Cost Offset With Quadruple Therapy for Heart Failure"],"prefix":"10.1001","volume":"11","author":[{"given":"Mohammad","family":"Keykhaei","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Geffen School of Medicine at University of California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sina","family":"Rashedi","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Greene","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Duke University School of Medicine, Durham, North Carolina"},{"name":"Duke Clinical Research Institute, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clyde","family":"Yancy","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boback","family":"Ziaeian","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Geffen School of Medicine at University of California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander T.","family":"Sandhu","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Geffen School of Medicine at University of California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Kittleson","sequence":"additional","affiliation":[{"name":"Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregg C.","family":"Fonarow","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Geffen School of Medicine at University of California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"12 pt 2","key":"hbr260016r1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacadv.2025.102303","article-title":"Rising trends in obesity and heart failure: related mortality in the United States, 1999-2024.","volume":"4","author":"Sajid","year":"2025","journal-title":"JACC Adv"},{"issue":"11","key":"hbr260016r2","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1056\/NEJMoa1409077","article-title":"Angiotensin-neprilysin inhibition versus enalapril in heart failure.","volume":"371","author":"McMurray","year":"2014","journal-title":"N Engl J Med"},{"issue":"9146","key":"hbr260016r3","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/S0140-6736(98)11181-9","article-title":"The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial.","volume":"353","year":"1999","journal-title":"Lancet"},{"issue":"1","key":"hbr260016r4","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1056\/NEJMoa1009492","article-title":"Eplerenone in patients with systolic heart failure and mild symptoms.","volume":"364","author":"Zannad","year":"2011","journal-title":"N Engl J Med"},{"issue":"21","key":"hbr260016r5","doi-asserted-by":"publisher","first-page":"1995","DOI":"10.1056\/NEJMoa1911303","article-title":"Dapagliflozin in patients with heart failure and reduced ejection fraction.","volume":"381","author":"McMurray","year":"2019","journal-title":"N Engl J Med"},{"issue":"15","key":"hbr260016r6","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1056\/NEJMoa2022190","article-title":"Cardiovascular and renal outcomes with empagliflozin in heart failure.","volume":"383","author":"Packer","year":"2020","journal-title":"N Engl J Med"},{"issue":"2","key":"hbr260016r7","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1007\/BF02915250","article-title":"Cost-effectiveness of spironolactone in patients with severe heart failure.","volume":"172","author":"Tilson","year":"2003","journal-title":"Ir J Med Sci"},{"issue":"9","key":"hbr260016r8","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1161\/01.CIR.0000157146.86758.BC","article-title":"Cost-effectiveness of eplerenone compared with placebo in patients with myocardial infarction complicated by left ventricular dysfunction and heart failure.","volume":"111","author":"Weintraub","year":"2005","journal-title":"Circulation"},{"issue":"8","key":"hbr260016r9","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1002\/ejhf.2940","article-title":"The cost-effectiveness of dapagliflozin in heart failure with preserved or mildly reduced ejection fraction: a European health-economic analysis of the DELIVER trial.","volume":"25","author":"Booth","year":"2023","journal-title":"Eur J Heart Fail"},{"issue":"10","key":"hbr260016r10","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.125.012936","article-title":"Get With The Guidelines-Heart Failure: twenty years in review, lessons learned, and the road ahead.","volume":"18","author":"Tang","year":"2025","journal-title":"Circ Heart Fail"},{"issue":"1","key":"hbr260016r11","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1161\/CIRCOUTCOMES.110.957225","article-title":"Lifetime costs of medical care after heart failure diagnosis.","volume":"4","author":"Dunlay","year":"2011","journal-title":"Circ Cardiovasc Qual Outcomes"},{"issue":"1","key":"hbr260016r12","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.cardfail.2025.01.029","article-title":"Impact of embedded interdisciplinary heart failure teams on achieving guideline-directed medical therapy within community-based cardiology practices.","volume":"32","author":"Bregier","year":"2026","journal-title":"J Card Fail"},{"issue":"2","key":"hbr260016r13","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.123.030952","article-title":"Challenge of Optimizing Medical Therapy in Heart Failure: Unlocking the Potential of Digital Health and Patient Engagement.","volume":"13","author":"Azizi","year":"2024","journal-title":"J Am Heart Assoc"}],"container-title":["JAMA Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamacardiology\/articlepdf\/2850258\/jamacardiology_keykhaei_2026_br_260016_1786123793.12233.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T15:00:41Z","timestamp":1786546841000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamacardiology\/fullarticle\/2850258"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,1]]},"references-count":13,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamacardio.2026.1552","relation":{},"ISSN":["2380-6583"],"issn-type":[{"value":"2380-6583","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8,1]]}}}