Effectiveness of SGLT2 inhibitor therapy in treatment of Heart failure: A Meta-Analysis

Abstract Aim We conducted a meta-analysis on the effectiveness of sodium-glucose co-transporter 2 (SGLT2) inhibitors in heart failure (HF) patients with preserved (HFpEF) and reduced (HFrEF) ejection fraction. Methods A comprehensive search of several databases for placebo-controlled randomised controlled trials of SGLT2 inhibitors from inception to September 30 2022, limited to English language and excluding animal studies, was conducted. The databases included Medline, Scopus, Cochrane Central, and ClinicalTrials.gov. Randomised controlled studies were chosen if they included HF patients and reported at least one of the predetermined outcomes. Hazard ratios (HRs) or risk ratios were pooled together with the appropriate 95% confidence intervals using a random-effect model. Fourteen trials met the inclusion criteria, with 42 409 HF patients participating (N = 21 678 in the SGLT2 inhibitor arms and N = 20 731 in the placebo arms). Results SGLT2 inhibitors significantly reduced the composite of HF hospitalisation or cardiovascular death [HR: 0.75 (0.71–0.79); P < 0.001; I 2 = 0%], total hospitalisations for heart failure [HR: 0.70 (0.66– 0.75); P < 0.001; I 2 = 0%], and reduced the occurrence of cardiovascular death [HR: 0.86 (0.81–0.92); P < 0.001; I 2 = 43%]. Sub-group analysis was conducted based on HF status at baseline, EF, diabetes status at baseline, and sex. SGLT2 inhibitors significantly reduced the composite heart failure hospitalisation and cardiovascular death for all the subgroups except for patients with HFpEF at baseline [HR: 0.87 (0.74– 1.03); P = 0.11; I 2 = 60%] and no diabetes status at baseline [HR: 0.92 (0.73–1.16); P = 0.50; I 2 = 78%]. Conclusions In patients with HF, SGLT2 inhibitors may significantly improve clinical outcomes, including all-cause and cardiovascular mortality. In this meta-analysis, SGLT2 inhibitors did not show a reduction in composite heart failure in patients with heart failure with preserved ejection fraction at baseline.