{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T23:19:46Z","timestamp":1784762386480,"version":"3.55.0"},"reference-count":85,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>The study evaluated the cardiovascular outcomes associated with pharmacological treatments in heart failure (HF) patients and explored whether the benefits\/risks associated with these drugs for HF with mildly reduced or preserved ejection fraction (HFmrEF\/HFpEF) were consistent with HF with reduced EF (HFrEF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Several online databases were searched. All studies explored the cardiovascular effects of sodium glucose cotransporter-2 inhibitor (SGLT2i), sacubitril\/valsartan, omecamtiv mecarbil and vericiguat were screened and reviewed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 39 studies were included. Compared with placebo therapy, SGLT2i significantly reduced cardiovascular death and hospitalization for HF (HHF) in both HFrEF and HFmrEF\/HFpEF patients (approximately 13%\u201327% risk reduction). SGLT2i reduced serious adverse events across all HF types. Sacubitril\/valsartan demonstrated significant benefits in HFrEF patients, reducing cardiovascular death by 19%, all-cause mortality by 22%, and HHF by 22%. However, these benefits were not observed in HFmrEF\/HFpEF patients. In contrast, sacubitril\/valsartan substantially increased hypotension risk in HFmrEF\/HFpEF patients. Omecamtiv mecarbil and vericiguat tended to improve cardiovascular outcomes in patients with HF, but the difference was not statistically significant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SGLT2i represents an effective and safe treatment strategy across the HF spectrum. Sacubitril\/valsartan significantly improves outcomes in HFrEF but requires careful benefit-risk evaluation in HFmrEF\/HFpEF patients. Current evidence does not support routine use of omecamtiv mecarbil or vericiguat. Large-scale randomized trials are warranted to validate these findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>CRD42023455966.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1644757","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T05:22:17Z","timestamp":1770355337000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Differential cardiovascular benefits of SGLT2 inhibitors, sacubitril\/valsartan, omecamtiv mecarbil, and vericiguat across heart failure phenotypes: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Meng","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, West China Second University Hospital, Sichuan University\/Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Zuo","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Xiangya Hospital, Central South University","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1007\/s10557-020-07099-2","article-title":"Relative efficacy of sacubitril-valsartan, vericiguat, and SGLT2 inhibitors in heart failure with reduced ejection fraction: a systematic review and network meta-analysis","volume":"35","author":"Aimo","year":"2021","journal-title":"Cardiovasc Drugs Ther."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1016\/j.jacc.2024.02.035","article-title":"Sacubitril\/valsartan-related hypotension in patients with heart failure and preserved or mildly reduced ejection fraction","volume":"83","author":"Alberto","year":"2024","journal-title":"J. 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