Meta-analysis on the effectiveness of SGLT2 inhibitors in heart failure

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. Aims We aimed to carry out a meta-analysis on the effectiveness of sodium-glucose co transporter 2 (SGLT2) inhibitors in heart failure patients (HF) with preserved and reduced ejection fraction. Methods and results From their inception till September 2022, MEDLINE, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov were searched for placebo-controlled randomized controlled trials of SGLT2 inhibitors. Randomized controlled studies were chosen if they included HF patients and reported at least one of the predetermined outcomes. A random effects model was used to pool hazard ratios (HRs) or risk ratios together with the appropriate 95% confidence intervals. There were fourteen trials in total, with 42409 HF patients participating (N = 21678 in the SGLT2 inhibitor arms and N = 20731 in the placebo arms). In the overall HF cohort, SGLT2 inhibitors significantly reduced the composite of first HF hospitalization or cardiovascular death [HR: 0.75 (0.71–0.79); P <0.001; I2 = 0%]. Also resulted in a significant reduction in total hospitalizations for heart failure [HR: 0.70 (0.66–0.75); P < 0.001; I2 = 0%] and reduced the occurrence of cardiovascular death [HR: 0.86 (0.81–0.92); P < 0.001; I2 = 43%]. Sub-group analysis was conducted to based on HF status at baseline, ejection fraction, diabetes status at baseline, and gender. SGLT2 inhibitors significantly reduced the composite heart failure hospitalization and cardiovascular death for all the subgroups except for patients with HFpEF at baseline [HR: 0.87 (0.74–1.03); P = 0.11; I2 = 60%] and no diabetes status at baseline [HR: 0.92 (0.73–1.16); P = 0.50; I2 = 78%]. SGLT2 inhibitors seemed to have no risk of hypovolaemia, hyperkalaemia, or hypotension when compared to the placebo. Conclusions In patients with HF, SGLT2 inhibitors substantially increase cardiovascular outcomes, including all-cause and cardiovascular mortality. In this meta-analysis, SGLT2 inhibitors did not show reduction in composite heart failure in patients with heart failure with preserved ejection fraction (HFpEF) at baseline.