Key result
SGLT2 inhibitors cut CV death or HF hospitalization ~23% in ischemic patients with similar non-ischemic benefit.
Why the study?
The safety and efficacy of SGLT2 inhibitors in heart failure across different etiologies were uncertain.
Do SGLT2 inhibitors reduce cardiovascular death or heart failure hospitalization in heart failure patients with ischemic and non-ischemic etiologies?
Meta-Analysis (n=15,676)
Do SGLT2 inhibitors reduce cardiovascular death or heart failure hospitalization in heart failure patients with ischemic and non-ischemic etiologies?
Effect estimate: HR 0.77 (95% CI 0.70-0.86)
p-value: p=<0.00001
SGLT2 inhibitors significantly reduce the composite of cardiovascular death or heart failure hospitalization in patients with heart failure, with consistent benefits regardless of whether the etiology is ischemic or non-ischemic.
Supports SGLT2 inhibitor use in heart failure regardless of etiology; confirms consistent benefit across ischemic and non-ischemic subgroups.
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.
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Siddiqui et al. (2025) conducted a meta-analysis in Heart failure with ischemic and non-ischemic etiologies (n=15,676). SGLT2 inhibitors (empagliflozin, dapagliflozin, sotagliflozin) vs. Placebo was evaluated on Composite of cardiovascular death or hospitalization due to heart failure (CVD/HHF) in ischemic patients (HR 0.77, 95% CI 0.70-0.86, p=<0.00001). SGLT2 inhibitors significantly reduced the composite of cardiovascular death or heart failure hospitalization in both ischemic (HR 0.77) and non-ischemic (HR 0.72) patients, with no significant subgroup difference.
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