Short-term survival of dual SGLT2i-MRA and four-class guideline-directed medical therapy in acute heart failure

Recent clinical trials have underscored the importance of early initiation of heart failure (HF) guideline-directed medical therapy (GDMT), with growing emphasis on rapid sequencing, particularly after hospitalization for acute HF (AHF). Despite the proven short-term benefit of this approach, few patients receive this therapy at discharge. In patients with AHF, we evaluated whether treatment at discharge with dual sodium–glucose co-transporter-2 inhibitors (SGLT2i)–mineralocorticoid receptor antagonist (MRA) therapy or four-class GDMT was associated with short-term mortality and incremental risk reduction.

We analysed two prospective registries of AHF: the China HF-CAP (n = 441 320; main cohort) and the Swedish HF Registry (SwedeHF) (n = 2367; external validation cohort). We assessed the association between discharge prescription of dual therapy SGLT2i and MRA versus neither, and four-class GDMT vs none, with 90-day cardiovascular (CV) and all-cause mortalities, further stratified by baseline serum potassium levels and left ventricular ejection fraction (LVEF) categories.

In the main cohort, for dual SGLT2i and MRA therapy (n = 71 154) vs neither (n = 81 793) therapy, adjusted odds of 90-day CV and all-cause death were 0.320 [0.283–0.361] and 0.504 [0.472–0.539], respectively. In the external validation cohort, results were directionally consistent. Association between dual SGLT2i and MRA therapy and short-term survival was consistent irrespective of hyperkalaemia and across HF phenotypes. Further, in the main cohort, adjusted odds of 90-day CV death of four-class GDMT (n = 36 301) were 0.122 (0.106–0.14) vs no therapy (n = 18 374).

After AHF, early initiation of dual SGLT2i and MRA therapy was associated with lower short-term mortality, irrespective of LVEF or potassium levels. Four-class GDMT conferred the lowest risk, emphasizing the importance of timely implementation after AHF.