Factors affecting the efficacy of SGLT2is on heart failure events: a meta-analysis based on cardiovascular outcome trials

Background: The efficacy of sodium-glucose transporter 2 inhibitors (SGLT2is) on heart failure outcomes is unestablished in various subgroups defined by clinically important factors. We intended to evaluate the effects of six important factors on the efficacy of SGLT2is on heart failure outcomes. Methods: We included cardiovascular outcome trials (CVOTs) concerning SGLT2is. We assessed the heart failure composite outcome of cardiovascular death (CVD) or hospitalization for heart failure (HHF). Meta-analysis was conducted stratified by the following 6 factors: type of underlying diseases, type of SGLT2is, left ventricular ejection fraction (LVEF) level, New York Heart Association (NYHA) class, region, and race. Results: Ten CVOTs were included. Compared with placebo, SGLT2is reduced heart failure composite outcome by 25% [hazard ratio (HR) 0.75, 95% confidence interval (CI), 0.72-0.78] independent of type of underlying diseases, type of SGLT2is, LVEF level, and region (P-subgroup: 0.673, 0.244, 0.429, and 0.127, respectively). SGLT2is led to greater reduction in the composite outcome in patients with NYHA class II (HR 0.66, 95% CI, 0.59-0.74) than in patients with NYHA class III or IV (HR 0.86, 95% CI, 0.75-0.99; P-subgroup=0.004), and in Black (HR 0.63, 95% CI, 0.49-0.82) and Asian (HR 0.64, 95% CI, 0.53-0.77) patients than in White patients (HR 0.81, 95% CI, 0.76-0.86; P-subgroup=0.016). Conclusions: SGLT2is reduce heart failure composite outcome by 25% independent of type of underlying diseases, type of SGLT2is, LVEF level, and region. SGLT2is lead to greater reduction in the composite outcome in patients with NYHA class II than in patients with NYHA class III or IV, and in Black and Asian patients than in White patients.

Automated summary

SGLT2is independently reduce heart failure composite outcome by 25%, showing greater efficacy in patients with NYHA class II and in Black and Asian patients.