SGLT2 inhibitors reduced cardiovascular death by 12% (RR 0.88) and hospitalization for heart failure by 25% (RR 0.75) across heart failure phenotypes including HFrEF and HFmrEF/HFpEF patients.
Meta-Analysis
Do SGLT2 inhibitors, sacubitril/valsartan, omecamtiv mecarbil, and vericiguat improve cardiovascular outcomes across different heart failure phenotypes compared to placebo?
SGLT2 inhibitors provide consistent cardiovascular benefits across the entire heart failure spectrum, whereas the benefits of sacubitril/valsartan are restricted to HFrEF.
Effect estimate: RR 0.88 for cardiovascular death (95% CI 0.81–0.96), RR 0.75 for HHF (95% CI 0.70–0.80), RR 0.89 for all-cause mortality in HFrEF (95% CI 0.81–0.98) (95% CI Cardiovascular death: 0.81–0.96; HHF: 0.70–0.80; All-cause mortality (HFrEF): 0.81–0.98)
Aim The study evaluated the cardiovascular outcomes associated with pharmacological treatments in heart failure (HF) patients and explored whether the benefits/risks associated with these drugs for HF with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) were consistent with HF with reduced EF (HFrEF). Methods Several online databases were searched. All studies explored the cardiovascular effects of sodium glucose cotransporter-2 inhibitor (SGLT2i), sacubitril/valsartan, omecamtiv mecarbil and vericiguat were screened and reviewed. Results A total of 39 studies were included. Compared with placebo therapy, SGLT2i significantly reduced cardiovascular death and hospitalization for HF (HHF) in both HFrEF and HFmrEF/HFpEF patients (approximately 13%–27% risk reduction). SGLT2i reduced serious adverse events across all HF types. Sacubitril/valsartan demonstrated significant benefits in HFrEF patients, reducing cardiovascular death by 19%, all-cause mortality by 22%, and HHF by 22%. However, these benefits were not observed in HFmrEF/HFpEF patients. In contrast, sacubitril/valsartan substantially increased hypotension risk in HFmrEF/HFpEF patients. Omecamtiv mecarbil and vericiguat tended to improve cardiovascular outcomes in patients with HF, but the difference was not statistically significant. Conclusion SGLT2i represents an effective and safe treatment strategy across the HF spectrum. Sacubitril/valsartan significantly improves outcomes in HFrEF but requires careful benefit-risk evaluation in HFmrEF/HFpEF patients. Current evidence does not support routine use of omecamtiv mecarbil or vericiguat. Large-scale randomized trials are warranted to validate these findings. Systematic review registration CRD42023455966.
Wang et al. (Fri,) conducted a meta-analysis in Adults (≥18 years) with heart failure across the ejection fraction spectrum, including heart failure with reduced ejection fraction (HFrEF, LVEF ≤40%), and heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF, LVEF >40%). SGLT2 inhibitors vs. Placebo or standard therapy was evaluated on Cardiovascular death, hospitalization for heart failure (HHF), and all-cause mortality (RR 0.88 for cardiovascular death (95% CI 0.81–0.96), RR 0.75 for HHF (95% CI 0.70–0.80), RR 0.89 for all-cause mortality in HFrEF (95% CI 0.81–0.98), 95% CI Cardiovascular death: 0.81–0.96; HHF: 0.70–0.80; All-cause mortality (HFrEF): 0.81–0.98). SGLT2 inhibitors reduced cardiovascular death by 12% (RR 0.88) and hospitalization for heart failure by 25% (RR 0.75) across heart failure phenotypes including HFrEF and HFmrEF/HFpEF patients.
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