Dapagliflozin and New York Heart Association functional class in heart failure with mildly reduced or preserved ejection fraction: the DELIVER trial.

A meta‐analysis of the EMPEROR‐Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction) and DAPA‐HF (Dapagliflozin and Prevention of Adverse outcomes in Heart Failure) trials demonstrated a nominally significant treatment‐by‐subgroup interaction for NYHA functional class, with potentially less clinical benefit in those with NYHA class III/IV as compared with NYHA class II patients. 16 The observed discrepancy in the consistency of the effect of SGLT2i across NYHA function classes by HF phenotype may be attributable to differences in characteristics of the trial participants and/or pathophysiologic mechanisms in HFrEF as compared to HFpEF and HFmrEF.

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Participants with baseline NYHA class III/IV experienced higher rates of HF hospitalization (adjusted HR 1.15, 95% CI 0.98–1.36; p = 0.087) and cardiovascular death (adjusted HR 1.21, 95% CI 0.99–1.49; p = 0.062) compared with those with NYHA class II, but these did not reach statistical significance after covariate adjustment.

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