{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:13:16Z","timestamp":1791313996887,"version":"4.3.1"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:00:00Z","timestamp":1768694400000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Guideline\u2010directed medical therapy (GDMT) implementation in heart failure with reduced ejection fraction (HFrEF) remains suboptimal. A computable algorithm was developed to generate a medication optimization score (MOS) and provide guideline\u2010based recommendations. This computable algorithm was previously validated using clinical trial data, and an updated version was developed in 2021 to include sodium\u2010glucose co\u2010transporter 2 inhibitors. This study evaluated the association between the medication optimization information generated by this version of the algorithm and clinical outcomes using real\u2010world data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective cohort study of 1352 ambulatory adult patients with chronic HFrEF who received care from the advanced heart failure service at the University of Michigan between July 1, 2021, and October 14, 2024. The algorithm\u2010generated MOS was calculated using electronic health record data. The primary outcome was a composite of all\u2010cause mortality or hospitalization. Cox proportional hazards models were used to evaluate the association between baseline MOS and the primary outcome. A time\u2010varying Cox model using the running cumulative MOS and a marginal structural model (MSM) was also conducted. A linear mixed\u2010effects model was used to assess improvement in MOS over time as the secondary outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the analysis adjusted for HF severity and comorbidities, baseline MOS was associated with a lower hazard of the composite outcome (hazard ratio (HR) 0.96, 95% confidence interval (95% CI): 0.92, 0.99,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.040). In the cumulative time\u2010varying Cox model and the marginal structural model, the association with time\u2010varying MOS became stronger, with HRs of 0.88 (95% CI 0.81\u20130.95;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0015) and 0.88 (95% CI 0.83\u20130.93;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), respectively. The event rates per 100 person\u2010years were 44.1 in MOS 0%\u201333%, 39.5 in MOS 34%\u201366%, and 31.8 in MOS 67%\u2013100%. Longitudinally, MOS improved over time.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Higher algorithm\u2010generated MOS values were significantly associated with lower all\u2010cause mortality or hospitalization, and the MOS values increased over the follow\u2010up period. This suggested that this algorithm effectively identifies opportunities for GDMT optimization in real\u2010world clinical settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/phar.70101","type":"journal-article","created":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T16:55:56Z","timestamp":1768755356000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Association of an Algorithm\u2010Generated Medication Optimization Score With Clinical Outcomes in Ambulatory Patients With Heart Failure"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5685-147X","authenticated-orcid":false,"given":"Mohamed S.","family":"Ali","sequence":"first","affiliation":[{"name":"College of Pharmac University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3921-7091","authenticated-orcid":false,"given":"Kaitlyn M.","family":"Greer","sequence":"additional","affiliation":[{"name":"College of Pharmac University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1338-8385","authenticated-orcid":false,"given":"Sabah","family":"Ganai","sequence":"additional","affiliation":[{"name":"College of Pharmac University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5988-2405","authenticated-orcid":false,"given":"Todd M.","family":"Koelling","sequence":"additional","affiliation":[{"name":"Medical School University of Michigan  Ann Arbor Michigan USA"},{"name":"Frankel Cardiovascular Center University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0924-3135","authenticated-orcid":false,"given":"Scott L.","family":"Hummel","sequence":"additional","affiliation":[{"name":"Medical School University of Michigan  Ann Arbor Michigan USA"},{"name":"Frankel Cardiovascular Center University of Michigan  Ann Arbor Michigan USA"},{"name":"VA Ann Arbor Health System  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2910-1879","authenticated-orcid":false,"given":"Michael P.","family":"Dorsch","sequence":"additional","affiliation":[{"name":"College of Pharmac University of Michigan  Ann Arbor Michigan USA"},{"name":"Frankel Cardiovascular Center University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvac013"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)11181-9"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200105313442201"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199108013250502"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199108013250501"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)04440-2"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa010713"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909023411001"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1009492"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.23.2312"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1911303"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2022190"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30748-0"},{"key":"e_1_2_10_15_1","unstructured":"C. K.BreathettandV.Chair \u201cUpdate to the 2020 ACC\/AHA Clinical Performance and Quality Measures for Adults With Heart Failure \u201d(2024) https:\/\/professional.heart.org\/en\/\u2010\/media\/PHD\u2010Files\u20102\/Science\u2010News\/2\/2024\/2024\u2010ACC\u2010AHA\u2010HF\u2010PM\u2010Update\u2010Slides.pdf?sc_lang=enhttp:\/\/paperpile.com\/b\/fkNZiM\/qwSy."},{"key":"e_1_2_10_16_1","first-page":"65","article-title":"Managing Clinical Knowledge for Health Care Improvement","volume":"1","author":"Balas E. 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