{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T21:37:41Z","timestamp":1792705061935,"version":"4.5.0"},"reference-count":23,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ann Pharmacother"],"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Beta-blockers, selective (metoprolol succinate or bisoprolol) and nonselective (carvedilol), and angiotensin receptor-neprilysin inhibitors (ARNIs) are the first-line guideline-directed medical therapy for heart failure with reduced ejection fraction (HFrEF). Concomitant use of carvedilol and ARNI (sacubitril\/valsartan) may result in additive vasodilatory effects, which may increase the risk of hypotension and limit dose titration of sacubitril\/valsartan.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>This study examines differences in clinical endpoints between selective and nonselective beta-blocker therapy among patients with HFrEF receiving sacubitril\/valsartan.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>This retrospective cohort study utilized TriNetX Research Collaborative real-world data. Patients receiving sacubitril\/valsartan concomitantly with carvedilol were identified as the intervention cohort, while those receiving metoprolol succinate or bisoprolol served as controls. The primary endpoint was a composite of all-cause mortality or all-cause hospitalization during the 3-year follow-up. Propensity score matching (PSM) balanced confounders. Kaplan-Meier analyses were used to estimate event-free survival, and hazard ratios (HRs) were calculated using Cox proportional hazards models for time-to-event outcomes. Sensitivity analyses were conducted to evaluate the robustness of the findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Overall, 75 230 patients received carvedilol and 21 587 received metoprolol\/bisoprolol. After PSM, 20 939 patients were included in each group. Carvedilol was associated with a higher risk of the primary composite endpoint compared with those taking metoprolol or bisoprolol (52.32% vs 46.29%; HR: 1.21; 95% CI, 1.17-1.24;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .0001). Carvedilol was also linked to increased hospitalization risk (HR: 1.32; 95% CI, 1.28-1.36;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .0001) but a modest reduction in mortality (HR: 0.92; 95% CI, 0.87-0.97;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .0011). In addition, carvedilol was associated with higher risks of hypotension, end-stage renal disease, and bradycardia. Sensitivity analysis results were consistent for the primary endpoint.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Relevance:<\/jats:title>\n                    <jats:p>Our results suggest that carvedilol may be associated with a higher risk of the composite endpoint, health care utilization, and adverse events but lower all-cause mortality compared with metoprolol or bisoprolol in patients with HFrEF taking sacubitril\/valsartan.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10600280261493520","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T05:54:06Z","timestamp":1792475646000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of Clinical Outcomes of Selective Versus Nonselective Beta-Blockers Among Patients With Heart Failure With Reduced Ejection Fraction Receiving Sacubitril\/Valsartan"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3689-454X","authenticated-orcid":false,"given":"Leonie","family":"Adjeroh","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Systems and Policy, School of Pharmacy, West Virginia University, Morgantown, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid M.","family":"Kamal","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Systems and Policy, School of Pharmacy, West Virginia University, Morgantown, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Raymond Guo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Systems and Policy, School of Pharmacy, West Virginia University, Morgantown, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudarshan","family":"Balla","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Thoracic Surgery, Heart &amp; Vascular Institute, West Virginia University, Morgantown, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijin","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health, West Virginia University, Morgantown, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Kido","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, School of Pharmacy, West Virginia University, Morgantown, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,10,19]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001063"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2023.12.024"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/cvm-2-1-020"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.283.10.1295"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)11181-9"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfr020"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13800-7"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1409077"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1516126"},{"key":"e_1_3_5_11_2","unstructured":"TriNetX. 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Accessed February 11 2026. https:\/\/www.cdc.gov\/nccdphp\/divisions-offices\/about-the-division-of-nutrition-physical-activity-and-obesity.html"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000628"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000310"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.04.079"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajhp\/61.12.1289"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2018.01.005"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2014.3258"},{"key":"e_1_3_5_23_2","unstructured":"ClinicalTrials.gov. Comparative effectiveness of carvedilol versus metoprolol succinate in heart failure patients with an implantable cardioverter defibrillator (Clinicaltrials.gov Identifier NCT06964464). 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