The PARAGON-HF trial reported a highly significant treatment-by-sex interaction, with women showing a greater decrease in cardiovascular death and hospitalization for HF than men when treated with a neprilysin inhibitor (treatment-by-sex interaction, P=0.021).8 Furthermore, that trial reported a meaningful treatment–by–sex–by–ejection fraction interaction; that is, women showed a more favorable treatment effect than men up to higher values for ejection fraction (eg, ejection fractions between 55% and 60%). This evidence concerns the gene MME and hydrops fetalis.