Safety and efficacy of SGLT2 inhibitors in heart failure patients with ischemic and non-ischemic etiologies: a systematic review and meta-analyses.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) show promise as a therapy for heart failure (HF); however, the safety and efficacy of SGLT2i in different HF etiologies are uncertain, thus arising the need for a meta-analyses.

Main Text: PubMed and Scopus were queried until May 2023 for studies comparing SGLT2i with placebo in HF patients with ischemic and non-ischemic etiologies. Meta-analyses were performed using risk ratio and hazard ratio. A fixed effect model was used. Outcomes assessed were hospitalization due to HF (HHF), cardiovascular death (CVD), CVD/HHF, all-cause mortality, volume depletion, fracture, and discontinuation of drug due to adverse effects. Four RCTs were included (15,676 patients). Analysis revealed no significant differences in CVD/HHF between ischemic [HR: 0.77 (0.70-0.86) P < 0.00001] and non-ischemic patients [HR: 0.72 (0.65-0.80) P < 0.00001] using SGLT2i (P = 0.35). Significant reductions were seen in HHF in both ischemic [RR 0.74 (0.65-0.84) P < 0.00001] and non-ischemic [RR 0.68 (0.59-0.78) P < 0.00001] patients (P = 0.39), with the effect more notable in the non-ischemic cohort. However, CVD significantly decreased in non-ischemic patients [RR 0.78 (0.63-0.95) P = 0.01], whereas no significant reduction was noted in ischemic patients [RR 0.94 (0.80-1.10) P = 0.43] (P-interaction = 0.15). All-cause mortality was significantly reduced in non-ischemic patients [RR 0.80 (0.67-0.96) P = 0.02] but not in ischemic patients [RR 0.96 (0.83-1.10) P = 0.52]. No significant safety events were observed in the SGLT2i cohort including volume depletion [RR 1.08 (0.94-1.25) P = 0.26], fracture [RR 1.02 (0.77-1.36) P = 0.88], or discontinuation of drug due to adverse effects [RR 0.97 (0.86-1.10) P = 0.65].

Conclusion: Similar CVD/HHF outcomes for ischemic and non-ischemic patients with SGLT2i. Significant HHF reductions in both groups. Non-ischemic patients showed greater improvements in CVD and all-cause mortality. However, no subgroup difference between ischemic and non-ischemic cause of heart failure was noted in our analysis.