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

Siddiqui HF, Khan AB, Nasir MM, Hashmi T, Siddiqui AF, Asim H, Siddiqui BI

The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology, 2025

15,676 participants · 1 citation

Abstract

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…

How strong is the evidence?

Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 15,676 participants or records.

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