Key result
In patients with HFrEF, SGLT2 inhibitors significantly reduced the risk of cardiovascular death or HF hospitalization compared with placebo (RR 0.77; 95% CI 0.71-0.83).
Why the study?
New therapies (SGLT2i, vericiguat, and omecamtiv mecarbil) show clinical benefits in HFrEF without acting primarily through neuro-hormonal blockade, but their relative efficacies remain unclear.
Do new heart failure therapies (SGLT2 inhibitors, vericiguat, omecamtiv mecarbil) reduce cardiovascular death or heart failure hospitalization in patients with HFrEF on standard-of-care therapy?
Meta-Analysis (n=23,861)
Do new heart failure therapies (SGLT2 inhibitors, vericiguat, omecamtiv mecarbil) reduce cardiovascular death or heart failure hospitalization in patients with HFrEF on standard-of-care therapy?
Relative Risk: 0.77 (95% CI 0.71–0.83)
A network meta-analysis demonstrates that SGLT2 inhibitors are the most effective among newer therapies (compared to vericiguat and omecamtiv mecarbil) for reducing cardiovascular death and heart failure hospitalization in patients with HFrEF.
SGLT2i reduce CVD-HF risk versus vericiguat or omecamtiv mecarbil in HFrEF; reinforces their priority among newer agents.
BACKGROUND: The new heart failure (HF) therapies of sodium-glucose cotransporter 2 inhibitors (SGLT2i), vericiguat, and omecamtiv mecarbil do not act primarily through the neuro-hormonal blockade, but have shown clinical benefits in patients with HF with reduced ejection fraction (HFrEF). However, their respective efficacies remain unclear. Our aim was to evaluate the relative efficacy of new drugs for HFrEF. METHODS: We performed a network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing SGLT2i, vericiguat, omecamtiv mecarbil, and placebo in HFrEF patients. The primary endpoint was the composite of cardiovascular death (CVD) or HF hospitalization (CVD-HF); secondary endpoints were CVD, all-cause death, and HF hospitalization (HFH). RESULTS: = 23,861 patients) were included. A significant reduction in CVD-HF was observed with SGLT2i compared with placebo (risk ratio (RR) 0.77, 95% confidence interval (CI) 0.71-0.83), vericiguat (RR 0.84, 95% CI 0.75-0.93), and omecamtiv mecarbil (RR 0.80, 95% CI 0.72-0.88). No significant difference was observed between vericiguat and omecamtiv mecarbil (RR 0.95, 95% CI 0.87-1.04). SGLT2i were superior to placebo and omecamtiv mecarbil for all individual secondary endpoints (CVD, all-cause death, and HFH), and also to vericiguat for HFH. SGLT2i ranked as the most effective therapy for all endpoints, and vericiguat, omecamtiv mecarbil, and placebo ranked as the second, third, and last options, respectively, for the primary endpoint. CONCLUSIONS: In patients with HFrEF on standard-of-care therapy, SGLT2i therapy was associated with a reduced risk of CVD-HF compared to placebo, vericiguat, and omecamtiv mecarbil. Furthermore, SGLT2i were superior to placebo and omecamtiv mecarbil for CVD, all-cause death, and HFH, and also to vericiguat for HFH.
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Pagnesi et al. (2022) conducted a meta-analysis in Heart failure with reduced ejection fraction (HFrEF) (n=23,861). SGLT2 inhibitors vs. Placebo, vericiguat, and omecamtiv mecarbil was evaluated on Composite of cardiovascular death (CVD) or HF hospitalization (CVD-HF) (RR 0.77, 95% CI 0.71-0.83). In patients with HFrEF, SGLT2 inhibitors significantly reduced the risk of cardiovascular death or HF hospitalization compared with placebo (RR 0.77; 95% CI 0.71-0.83).
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