Why the study?
Both SGLT-2 inhibitors and ARNI are recommended for HFrEF, but no trial had assessed the efficacy and safety of their combined therapy.
Does combined therapy of SGLT-2 inhibitors and ARNI reduce the composite risk of cardiovascular death or hospitalization for heart failure in patients with HFrEF compared to monotherapy?
Does combined therapy of SGLT-2 inhibitors and ARNI reduce the composite risk of cardiovascular death or hospitalization for heart failure in patients with HFrEF compared to monotherapy?
Combined therapy with SGLT-2 inhibitors and ARNI provides additional cardiovascular benefits over monotherapy in patients with HFrEF, though it is associated with a higher risk of volume depletion.
Answers are grounded in this paper and cite their sources.
Supports combined SGLT2i-ARNI use in HFrEF; extends prespecified subgroup data from two major RCTs to reinforce foundational therapy.
Background Both sodium-glucose co-transporter-2 (SGLT-2) inhibitors and angiotensin receptor-neprilysin inhibitor (ARNI) were recommended to treat heart failure with reduced ejection fraction (HFrEF). However, no trial was conducted to assess the efficacy and safety of the combined therapy of SGLT-2 inhibitors and ARNI in patients with HFrEF. Methods We performed a meta-analysis of the prespecified subgroups from DAPA-HF and EMPEROR-Reduced trials. The primary endpoint was the composite risk of cardiovascular death or hospitalization for heart failure. The risk of cardiovascular death, all-cause death, a composite of serious adverse renal outcomes, and volume depletion were also estimated. Results The risk of the composite of cardiovascular death or hospitalization for heart failure was reduced in combined therapy of SGLT-2 inhibitors and ARNI, compared with ARNI monotherapy (RR.68, 95% CI.53 to.85, P = 0.001). When compared with SGLT-2 inhibitors monotherapy, the events of cardiovascular death (RR.64, 95% CI.46 to 0.87, P = 0.005) and all-cause death (RR.72, 95% CI.55 to.94, P = 0.01) were significantly less in combined therapy, accompanied by elevated incidence of volume depletion (RR 1.55, 95% CI 1.22 to 1.96, P = 0.0003). Conclusion Combined therapy has additional benefits over monotherapy in patients with HFrEF, however, it is accompanied by a possibly higher risk of volume depletion.
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Lin et al. (2022) studied this question.
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