PMID- 34308311 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231107 IS - 2589-5370 (Electronic) IS - 2589-5370 (Linking) VI - 36 DP - 2021 Jun TI - SGLT2 inhibitors decrease cardiovascular death and heart failure hospitalizations in patients with heart failure: A systematic review and meta-analysis. PG - 100933 LID - 10.1016/j.eclinm.2021.100933 [doi] LID - 100933 AB - BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the composite of heart failure (HF) hospitalizations or cardiovascular mortality among patients with HF. However, the efficacy of SGLT2 inhibitors in secondary endpoints of randomized trials and in subgroups of HF patients is not well known. METHODS: We performed a systematic review and meta-analysis of placebo-controlled, randomized trials of SGLT2 inhibitors in patients with HF. PubMed, Embase, and Cochrane databases were searched for trials published up to January 21, 2021. Data were extracted from published reports and quality assessment was performed per Cochrane recommendations. Hazard ratios (HRs) with 95% CI were pooled across trials. The primary endpoints of interest were all-cause and cardiovascular mortality. RESULTS: Out of 3969 database results, 15 randomized trials and 20,241 patients were included; 10,594 (52.3%) received SGLT2 inhibitors. All-cause mortality (HR 0.86; 95% CI 0.79-0.94; p = 0.0007; I(2)=0%) and cardiovascular mortality (HR 0.86; 95% CI 0.78-0.96; p = 0.006; I(2)=0%) were significantly lower in patients treated with SGLT2 inhibitors compared with placebo. The composite of cardiovascular mortality, HF hospitalizations, or urgent visits for HF was significantly reduced with SGLT2 inhibitors in all the following subgroups: male, female, age < 65, age >/= 65, race - Black and White, estimated glomerular filtration rate (eGFR) <60, eGFR >/=60, New York Heart Association (NYHA) class II, NYHA >/=III, and HF with preserved ejection fraction. INTERPRETATION: In patients with HF, SGLT2 inhibitors significantly reduce all-cause and cardiovascular mortality compared with placebo. In addition, the composite of cardiovascular mortality or HF hospitalizations/urgent visits is reduced with SGLT2 inhibitors across subgroups of sex, age, race, eGFR, HF functional class, and ejection fraction. CI - (c) 2021 The Author(s). FAU - Cardoso, Rhanderson AU - Cardoso R AD - Heart and Vascular Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States. FAU - Graffunder, Fabrissio P AU - Graffunder FP AD - Division of Medicine, Federal University of Santa Catarina, Florianopolis, Brazil. FAU - Ternes, Caique M P AU - Ternes CMP AD - Division of Medicine, Federal University of Santa Catarina, Florianopolis, Brazil. AD - Cardiac Arrhythmia Service, SOS Cardio Hospital, Florianopolis, Brazil. FAU - Fernandes, Amanda AU - Fernandes A AD - Division of Medicine, University of Miami, Miami, United States. FAU - Rocha, Ana V AU - Rocha AV AD - Division of Medicine, Federal University of Goias, Goiania, Brazil. FAU - Fernandes, Gilson AU - Fernandes G AD - Division of Cardiology, University of Miami, Miami, United States. FAU - Bhatt, Deepak L AU - Bhatt DL AD - Heart and Vascular Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States. LA - eng PT - Journal Article DEP - 20210605 PL - England TA - EClinicalMedicine JT - EClinicalMedicine JID - 101733727 PMC - PMC8257984 OTO - NOTNLM OT - DM, diabetes mellitus OT - HF, heart failure OT - HFpEF, heart failure with preserved ejection fraction OT - HR, hazard ratio OT - Heart failure OT - LVEF, left ventricular ejection fraction OT - NYHA, New York Heart Association OT - OR, odds ratio OT - RCTs, randomized controlled trials OT - SGLT2 inhibitors OT - SGLT2, sodium-glucose cotransporter 2 OT - Type 2 Diabetes OT - cardiovascular risk OT - eGFR, estimated glomerular filtration rate COIS- Dr. Bhatt reports grants from Amarin, grants from AstraZeneca, grants from Bristol-Myers Squibb, grants from Eisai, grants from Ethicon, grants from Medtronic, grants from sanofi aventis, grants from The Medicines Company, other from FlowCo, grants and other from PLx Pharma, other from Takeda, personal fees from Duke Clinical Research Institute, personal fees from Mayo Clinic, personal fees from Population Health Research Institute, personal fees, non-financial support and other from American College of Cardiology, personal fees from Belvoir Publications, personal fees from Slack Publications, personal fees from WebMD, personal fees from Elsevier, other from Medscape Cardiology, other from Regado Biosciences, other from Boston VA Research Institute, personal fees and non-financial support from Society of Cardiovascular Patient Care, non-financial support from American Heart Association, personal fees from HMP Global, grants from Roche, personal fees from Harvard Clinical Research Institute (now Baim Institute for Clinical Research), other from Clinical Cardiology, personal fees from Journal of the American College of Cardiology, other from VA, grants from Pfizer, grants from Forest Laboratories/AstraZeneca, grants from Ischemix, other from St. Jude Medical (now Abbott), other from Biotronik, grants and other from Cardax, other from Boston Scientific, grants from Amgen, grants from Lilly, grants from Chiesi, grants from Ironwood, personal fees from Cleveland Clinic, personal fees from Mount Sinai School of Medicine, other from Merck, grants from Abbott, grants from Regeneron, other from Svelte, grants and other from PhaseBio, grants from Idorsia, grants from Synaptic, personal fees from TobeSoft, grants, personal fees and other from Boehringer Ingelheim, personal fees from Bayer, grants and other from Novo Nordisk, grants from Fractyl, personal fees from Medtelligence/ReachMD, personal fees from CSL Behring, other from Cereno Scientific, grants from Afimmune, personal fees from Ferring Pharmaceuticals, other from CSI, grants from Lexicon, personal fees from MJH Life Sciences, personal fees from Level Ex, personal fees from Contego Medical, personal fees from CellProthera, personal fees from K2P, personal fees from Canadian Medical and Surgical Knowledge Translation Research Group, grants and other from MyoKardia/BMS, grants from Owkin, grants from HLS Therapeutics, grants from Janssen, outside the submitted work. All other authors have no disclosures. EDAT- 2021/07/27 06:00 MHDA- 2021/07/27 06:01 PMCR- 2021/06/05 CRDT- 2021/07/26 06:48 PHST- 2021/02/17 00:00 [received] PHST- 2021/05/11 00:00 [revised] PHST- 2021/05/13 00:00 [accepted] PHST- 2021/07/26 06:48 [entrez] PHST- 2021/07/27 06:00 [pubmed] PHST- 2021/07/27 06:01 [medline] PHST- 2021/06/05 00:00 [pmc-release] AID - S2589-5370(21)00213-3 [pii] AID - 100933 [pii] AID - 10.1016/j.eclinm.2021.100933 [doi] PST - epublish SO - EClinicalMedicine. 2021 Jun 5;36:100933. doi: 10.1016/j.eclinm.2021.100933. eCollection 2021 Jun.