Abstract
Abstract Background Sodium–glucose cotransporter 2 (SGLT-2) inhibitors have been found to decrease the incidence and progression of heart failure (HF) with reduced ejection fraction (EF). In the classification of HF, there is a gray zone between HF with reduced EF (EF <40%) and HF with preserved EF (EF >50%), which is named as HF with mildly reduced EF (EF between 40–50%). The effect of SGLT-2 inhibitors in mildly reduced EF HF patients have not yet been well established. We aimed to compare the composite outcomes, including cardiac death and re-hospitalization, between SGLT-2 inhibitors and placebo in this meta-analysis. Methods We searched MEDLINE, Scopus, EMBASE, Google Scholar, and the Cochrane Library for eligible studies. Of 167 eligible studies, three studies that compared the outcomes between SGLT-2 inhibitors and placebo in mildly reduced EF HF diabetic patients were included in this meta-analysis (n=928) (Table 1). Heterogeneity was assessed using High's I2, Egger's test and prediction intervals. The pooled effect size was calculated with a fixed-effect model. Due to the total number of studies was lower than 10, we did not report publication bias by drawing Funnel plot. Results Two studies were randomized controlled trial compared Sotagliflozin and placebo, and one study was an observational study with propensity score matched that compared SGLT-2 inhibitors with placebo. Patients using SGLT-2 inhibitors had lower primary composite end-points, such as cardiac death and re-hospitalization, than patients using placebo (HR= 0.69, 95% confidence intervals = 0.49–0.98, p value = 0.03) (Figure 1). There was no heterogeneity between studies, which was determined with High's I2 (0%) and Egger's test (p>0.05). Prediction interval was detected as a relatively wide that ranged between 0.30 and 1.58, which concluded that it could be expected to get the results within this range in future studies. Conclusion This meta-analysis indicated that the composite outcomes, including cardiac death and re-hospitalization, were lower in mildly reduced EF HF diabetic patients using SGLT-2 inhibitors when compared to placebo in such patients. Funding Acknowledgement Type of funding sources: None.
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