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Background <p>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.</p> Main text <p>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) <i>P</i> &lt; 0.00001] and non-ischemic patients [HR: 0.72 (0.65–0.80) <i>P</i> &lt; 0.00001] using SGLT2i (<i>P</i> = 0.35). Significant reductions were seen in HHF in both ischemic [RR 0.74 (0.65–0.84) <i>P</i> &lt; 0.00001] and non-ischemic [RR 0.68 (0.59–0.78) <i>P</i> &lt; 0.00001] patients (<i>P</i> = 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) <i>P</i> = 0.01], whereas no significant reduction was noted in ischemic patients [RR 0.94 (0.80–1.10) <i>P</i> = 0.43] (<i>P</i>-interaction = 0.15). All-cause mortality was significantly reduced in non-ischemic patients [RR 0.80 (0.67–0.96) <i>P</i> = 0.02] but not in ischemic patients [RR 0.96 (0.83–1.10) <i>P</i> = 0.52]. No significant safety events were observed in the SGLT2i cohort including volume depletion [RR 1.08 (0.94–1.25) <i>P</i> = 0.26], fracture [RR 1.02 (0.77–1.36) <i>P</i> = 0.88], or discontinuation of drug due to adverse effects [RR 0.97 (0.86–1.10) <i>P</i> = 0.65].</p> Conclusion <p>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.</p>

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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

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  • 发表日期：

    2025年3月19日

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  • Hasan Fareed Siddiqui,
  • Adam Bilal Khan,
  • Muhammad Moiz Nasir,
  • Taleen Hashmi,
  • Aisha Fareed Siddiqui,
  • Hanzla Asim,
  • Bushra Iqtidar Siddiqui

摘要

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.