Effects of natriuresis-guided diuretic therapy in men and women with acute heart failure: insights from PUSH-AHF

Abstract Aim Natriuresis-guided therapy has been proposed as a personalized approach for decongestion in acute heart failure (HF). Given the evidence of sex-related differences in response to decongestive therapy, we performed a sex-specific analysis on the treatment effect of natriuresis-guided therapy in the PUSH-AHF trial. Methods The PUSH-AHF trial randomized 310 patients (45% women) to natriuresis-guided therapy or standard of care (SOC). The endpoints of PUSH-AHF were compared between men and women. The 24-h natriuretic response was calculated as 24-h natriuresis divided by the total 24-h loop diuretic dose (mg of bumetanide equivalents). Results In men, mean total 24-h natriuresis was greater with natriuresis-guided therapy compared to SOC (443 vs. 354 mmol, p = 0.004), whereas in women, this was similar between the groups (357 vs. 336 mmol, p = 0.533, adjusted p -interaction = 0.276). The median 24-h natriuretic response was lower in women receiving natriuresis-guided therapy (23 vs. 52 mmol urinary sodium/mg bumetanide, p = 0.001) when compared to SOC, whereas in men, there was no significant difference between treatment arms (38 vs. 45 mmol respectively, p = 0.337, adjusted p -interaction = 0.009). Natriuresis-guided therapy was associated with a lower risk of 180-day HF rehospitalization or all-cause mortality in men (adjusted HR 0.51 (95% CI, 0.30–0.86; p = 0.011), but not in women (adjusted HR 1.40 (95% CI, 0.67–2.91; p = 0.368), adjusted p -interaction = 0.026). Conclusion Natriuresis-guided therapy was associated with greater natriuresis and a lower risk of 180-day all-cause mortality or HF rehospitalization in men but not in women. These exploratory sex-specific patterns warrant further investigation and confirmation.