SGLT2 inhibitors decrease cardiovascular death and heart failure hospitalizations in patients with heart failure: A systematic review and meta-analysis

Rhanderson Cardoso; Fabrissio P Graffunder; Caique M P Ternes; Amanda Fernandes; Ana V Rocha; Gilson Fernandes; Deepak L Bhatt

doi:10.1016/j.eclinm.2021.100933

SGLT2 inhibitors decrease cardiovascular death and heart failure hospitalizations in patients with heart failure: A systematic review and meta-analysis

EClinicalMedicine. 2021 Jun 5:36:100933. doi: 10.1016/j.eclinm.2021.100933. eCollection 2021 Jun.

Authors

Rhanderson Cardoso¹, Fabrissio P Graffunder², Caique M P Ternes^{2

3}, Amanda Fernandes⁴, Ana V Rocha⁵, Gilson Fernandes⁶, Deepak L Bhatt¹

Affiliations

¹ Heart and Vascular Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
² Division of Medicine, Federal University of Santa Catarina, Florianopolis, Brazil.
³ Cardiac Arrhythmia Service, SOS Cardio Hospital, Florianopolis, Brazil.
⁴ Division of Medicine, University of Miami, Miami, United States.
⁵ Division of Medicine, Federal University of Goias, Goiania, Brazil.
⁶ Division of Cardiology, University of Miami, Miami, United States.

Abstract

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; I²=0%) and cardiovascular mortality (HR 0·86; 95% CI 0·78-0·96; p = 0·006; I²=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.

Keywords: DM, diabetes mellitus; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HR, hazard ratio; Heart failure; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; OR, odds ratio; RCTs, randomized controlled trials; SGLT2 inhibitors; SGLT2, sodium-glucose cotransporter 2; Type 2 Diabetes; cardiovascular risk; eGFR, estimated glomerular filtration rate.