For patients with heart failure with reduced ejection fraction (HFrEF), treatment with sacubitril/valsartan may aid in reducing the requirement for loop diuretics compared with enalapril, according to the results of a follow-up analysis of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial.
In the original study, sacubitril/valsartan was found to reduce the primary composite outcome of cardiovascular death or hospitalization due to heart failure when compared with enalapril. This follow-up analysis aimed to determine whether diuretic dose requirement differences existed in patients treated with sacubitril/valsartan versus those treated with enalapril.
The trial included a total of 8,399 patients with New York Heart Association class II-IV heart failure with reduced left ventricular ejection fraction (LVEF). The patients were randomized to receive sacubitril/valsartan 200mg twice daily or enalapril 10mg 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),” the study authors explained. Percentages of patients who had increases or decreases in loop diuretic doses were calculated.
Baseline data revealed that 80.8% of patients were receiving diuretics, with 6290 taking loop diuretics (available dosage data for 5487) and 496 taking other diuretics. Average furosemide equivalent doses at baseline were reported as 48.2mg for the sacubitril/valsartan group and 49.6mg for the enalapril group (P= .25).
“Participants assigned to sacubitril/valsartan had more frequent diuretic dose reductions and less frequent dose increases compared to those taking enalapril at 6, 12, and 24 months,” the study authors reported. They added, “As a result, patients randomized to sacubitril/valsartan had lower use of diuretics at 6 months (net reduction 2.0%, P =.02), 12 months (net reduction 4.1%, P< .001) and 24 months (net reduction 6.1%, P< .001) relative to enalapril with similar differences seen in an on‐treatment analysis.”
These findings, the authors concluded, may be relevant to clinicians treating patients with HFrEF with concomitant sacubitril/valsartan and diuretics.
Vardeny, O. , Claggett, B. , Kachadourian, J. , Desai, A. S., Packer, M. , Rouleau, J. , Zile, M. R., Swedberg, K. , Lefkowitz, M. , Shi, V. , McMurray, J. J. and Solomon, S. D. (2019), Reduced loop diuretic use in patients taking sacubitril/valsartan compared with enalapril: the PARADIGM‐HF trial. Eur J Heart Fail. doi:10.1002/ejhf.1402