Sodium

Angiotensin-converting enzyme

Furosemide

Diuretic

Cardiology

Enalapril

Randomization

Bumetanide

Heart failure

Organic chemistry

Blood pressure

Sacubitril, Valsartan

Sacubitril

Internal medicine

Pharmacology

Medicine

Chemistry

Loop diuretic

Ejection fraction

Valsartan

Cotransporter

Randomized controlled trial

European Journal of Heart Failure

Aims To assess differences in diuretic dose requirements in patients treated with sacubitril/valsartan compared with enalapril in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM‐HF) trial. Methods and results Overall, 8399 patients with New York Heart Association class II–IV heart failure and reduced LVEF were randomized to sacubitril/valsartan 200 mg bid or enalapril 10 mg twice daily. Loop diuretic doses were assessed at baseline, 6, 12, and 24 months, and furosemide dose equivalents were calculated via multiplication factors (2x for torsemide and 40x for bumetanide). Percentages of participants with reductions or increases in loop diuretic dose were determined. At baseline, 80.8% of participants were taking any diuretics ( n = 6290 for loop diuretics, n = 496 for other diuretics); of those, recorded dosage data for loop diuretics were available on 5487 participants. Mean baseline furosemide equivalent doses were 48.2 mg for sacubitril/valsartan and 49.6 mg for enalapril ( P = 0.25). Patients treated with sacubitril/valsartan were more likely to reduce diuretic dose and less likely to increase diuretic dose relative to those randomized to enalapril at 6, 12, 24 months post‐randomization, with an overall decreased diuretic use of 2.0% ( P = 0.02), 4.1% ( P &lt; 0.001), and 6.1% ( P &lt; 0.001) at 6, 12, and 24 months, respectively, with similar findings in an on‐treatment analysis. Conclusion Treatment with sacubitril/valsartan was associated with more loop diuretic dose reductions and fewer dose increases compared with enalapril, suggesting that treatment with sacubitril/valsartan may reduce the requirement for loop diuretics relative to enalapril in patients with heart failure with reduced ejection fraction.

Reduced loop diuretic use in patients taking sacubitril/valsartan compared with enalapril: the PARADIGM‐HF trial