In patients with heart failure with preserved ejection fraction (HFpEF), treatment with sodium-glucose transporter 2 (SGLT-2) inhibitors may be beneficial, particularly for patients with diabetes. The use of SGLT-2 inhibitors has been linked to a reduced risk for hospitalization for HF, as well as improvements in HF severity and quality of life (QOL) among patients with HFpEF. These findings were published in the International Journal of Cardiology: Heart & Vasculature.
In the meta-analysis of randomized controlled trials (RCTs), the primary outcomes were cardiovascular (CV) outcomes, which included a composite of hospitalization for HF and CV death, hospitalization for HF, CV death, and all-cause death. Secondary outcomes included the severity of HF. To measure HF severity plasma B-type natriuretic peptide (BNP) levels, plasma N-terminal pro-BNP (NT-proBNP) levels, and exercise capacity evaluated with the 6-minute walk distance test were obtained. Additional outcomes of interest included QOL, according to the Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS), and hematocrit levels.
The meta-analysis included a total of 11 trials that involved 10,845 patients. Among these trials, 6 were HFpEF-specific studies and 5 were not. Of the total trials, 8 included patients with diabetes only, whereas the other 3 included both patients with and without diabetes. The definition of pEF across the trials started at greater than 40%.
Results of the study showed that treatment with SGLT-2 inhibitors significantly reduced the risk for a composite of hospitalization for HF and CV death (hazard ratio, 0.78; 95% CI, 0.70-0.87; Pfix <.001), as well as the risk for hospitalization for HF alone (odds ratio [OR], 0.71; 95% CI, 0.61-0.83; Pfix <.001). In contrast, SGLT-2 inhibitor use was not associated with a statistically significant reduced risk for CV death alone (OR, 0.95; 95% CI, 0.80-1.13; Pfix =.55) or risk for all-cause death (OR, 1.00; 95% CI, 0.87-1.13; P =.92).
Additionally, treatment with SGLT-2 inhibitors significantly decreased NT-proBNP levels (weighted mean difference [WMD], -60.16 pg/mL; 95% CI, -82.99 to -37.33 pg/mL; Pfix <.001), significantly increased 6-minute walk distance (WMD, 18.0 m; 95% CI, 6.8-29.3 m; Pfix =.002), and significantly increased KCCQ-TSS scores (WMD, 2.57 points; 95% CI, 0.19-4.96 points; Prandom =.035), compared with control patients.
SGLT-2 inhibitor use was not associated with a significant change in BNP levels compared with control patients (WMD, -7.53 pg/mL; 95% CI, -22.87 to 7.82 pg/mL; Pfix =.034). Further, SGLT-2 inhibitors significantly increased hematocrit levels compared with control patients (WMD, 2.34; 95% CI, 2.16-2.51; Pfix <.001).
There are several limitations to this study. To begin, the effect of SGLT-2 inhibitors in patients with diabetes and those without diabetes is not analyzed separately, since the meta-analysis comprised studies with patients with diabetes only, as well as studies that included both those with and those without diabetes. Additionally, since the meta-analyses utilized subgroup results of RCTs, including patients both with and those without HF, there may be bias.
“Our meta-analysis suggests that SGLT-2 inhibitors may reduce the risk of hospitalization for HF and may improve the severity of HF and QOL in HFpEF patients,” the study authors wrote. “Given the limited number of HFpEF specific trials in our meta-analysis, further large trials specifically designed for HFpEF are necessary to confirm our observed potential benefits of SGLT-2 inhibitors in HFpEF patients.”
Fukuta H, Hagiwara H, Kamiya T. Sodium-glucose cotransporter 2 inhibitors in heart failure with preserved ejection fraction: a meta-analysis of randomized controlled trials. Int J Cardiol Heart Vasc. Published online August 11, 2022. doi:10.1016/j.ijcha.2022.101103