{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:14:49Z","timestamp":1790802889715,"version":"4.1.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T00:00:00Z","timestamp":1657238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Heart Fail"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Physicians are sometimes reluctant to initiate guideline\u2010directed therapy in patients with heart failure and reduced ejection fraction (HFrEF) due to concerns of adverse events. We explored the risk of hypotension, volume depletion, and acute kidney injury (AKI) on sodium\u2013glucose cotransporter 2 (SGLT2) inhibitors in HFrEF populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      We determined summary risk ratios (RRs) by conducting a meta\u2010analysis on reported aforementioned adverse events on SGLT2 inhibitors from randomized controlled trials. We explored robustness of meta\u2010analyses by computing fragility and\/or reverse fragility index (FI or RFI) and its corresponding fragility quotient (FQ or RFQ) for each outcome. A total of 10\u2009050 patients with HFrEF entered the final meta\u2010analysis. Hypotension was reported in 4.5% (219\/4836) on SGLT2 inhibitors and in 4.1% (202\/4846) on placebo (RR 1.09, 95% confidence interval [CI] 0.91\u20131.31,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.36). An RFI of 21 and RFQ of 0.002 suggest robust findings for hypotension. Volume depletion occurred in 9.4% (473\/5019) on SGLT2 inhibitors and in 8.7% (438\/5031) on placebo (RR 1.07, 95% CI 0.95\u20131.21,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.25), respectively. RFI of 19 and RFQ of 0.001 suggest moderately robust findings for volume depletion. AKI was reported in fewer patients (1.9% [95\/4888]) on SGLT2 inhibitors than on placebo (2.8% [140\/4899]) providing lower incidence of AKI (RR 0.69, 95% CI 0.51\u20130.93,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.02). FI of 14 and RFQ of 0.001 suggest moderately robust findings for AKI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Sodium\u2013glucose cotransporter 2 inhibitor therapy is not associated with a clinically relevant risk of hypotension and volume depletion. Its use reduces the risk of AKI. This analysis supports current guideline recommendations on early use of SGLT2 inhibitors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2584","type":"journal-article","created":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T04:44:39Z","timestamp":1655873079000},"page":"1625-1632","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Side effects and treatment initiation barriers of sodium\u2013glucose cotransporter 2 inhibitors in heart failure: a systematic review and meta\u2010analysis"],"prefix":"10.1093","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7094-5961","authenticated-orcid":false,"given":"Davor","family":"Vukadinovi\u0107","sequence":"first","affiliation":[{"name":"Klinik f\u00fcr Innere Medizin III, Kardiologie Angiologie und Internistische Intensivmedizin, Universit\u00e4tsklinikum des Saarlandes, Universit\u00e4t des Saarlandes  Homburg\/Saar Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amr","family":"Abdin","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Innere Medizin III, Kardiologie Angiologie und Internistische Intensivmedizin, Universit\u00e4tsklinikum des Saarlandes, Universit\u00e4t des Saarlandes  Homburg\/Saar Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan D.","family":"Anker","sequence":"additional","affiliation":[{"name":"Department of Cardiology &amp; Berlin Institute of Health Center for Regenerative Therapies (BCRT) German Centre for Cardiovascular Research (DZHK), partner site Berlin, Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin (Campus CVK)  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe M.C.","family":"Rosano","sequence":"additional","affiliation":[{"name":"Centre for Clinical and Basic Research IRCCS San Raffaele Roma  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Mahfoud","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Innere Medizin III, Kardiologie Angiologie und Internistische Intensivmedizin, Universit\u00e4tsklinikum des Saarlandes, Universit\u00e4t des Saarlandes  Homburg\/Saar Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milton","family":"Packer","sequence":"additional","affiliation":[{"name":"Baylor Heart and Vascular Institute, Baylor University Medical Center  Dallas TX USA"},{"name":"Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javed","family":"Butler","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Mississippi Medical Center  Jackson MS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"B\u00f6hm","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Innere Medizin III, Kardiologie Angiologie und Internistische Intensivmedizin, Universit\u00e4tsklinikum des Saarlandes, Universit\u00e4t des Saarlandes  Homburg\/Saar Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,7,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504720"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1812389"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2022190"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1911303"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.2333"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-1096"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2017.08.015"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2021.07.049"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehaa496"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-151-4-200908180-00135"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d5928"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2019.03.012"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.048933"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.052186"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2030183"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.042929"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2021.01.017"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ehf2.13646"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2011.03.033"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2015.14"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1402"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.051783"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.047077"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000002492"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.116.004007"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw570"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht386"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2014.08.018"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(19)30256-6"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2024816"}],"updated-by":[{"DOI":"10.1002\/ejhf.2790","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T00:00:00Z","timestamp":1676592000000}}],"container-title":["European 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