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

Orly Vardeny, Brian Claggett, Jessica Kachadourian, Akshay S. Desai, Milton Packer, Jean Rouleau, Michael R. Zile, Karl Swedberg, Martin Lefkowitz, Victor Shi, John J.V. McMurray, Scott D. Solomon

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


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 < 0.001), and 6.1% (P < 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.

Original languageEnglish (US)
Pages (from-to)337-341
Number of pages5
JournalEuropean Journal of Heart Failure
Issue number3
StatePublished - Mar 2019

Bibliographical note

Funding Information:
This manuscript is the result of work supported with resources and use of facilities of the Minneapolis VA Health Care System. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. Conflict of interest: O.V., A.S.D., J.R., M.R.Z., K.S., J.J.V.Mc.M., and S.D.S. have consulted for or received research support from Novartis, sponsor of the PARADIGM-HF trial. S.D.S. has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Celladon, Cytokinetics, Eidos, Gilead, GSK, Ionis, Lone Star Heart, Mesoblast, MyoKardia, NIH/NHLBI, Sanofi Pasteur, Theracos, and has consulted for Akros, Alny-lam, Amgen, AstraZeneca, Bayer, BMS, Cardior, Corvia, Cytoki-netics, Gilead, GSK, Ironwood, Merck, Roche, Takeda, Ther-acos, Quantum Genetics, Cardurion, AoBiome, Janssen, Cardiac Dimensions outside the scope of this work. M.P. has consulted for Novartis, Actelion, Sanofi, Cardiokinetix, BioControl, Janssen, Amgen, AMAG, Daiichi, CardioMEMS, and Cardiorentis. J.J.V.Mc.M.’s employer, University of Glasgow, was paid by Novartis for his time spent as co-chairman of the PARADIGM-HF trial. J.K., M.L., and V.S. are employees of Novartis Pharmaceuticals Corporation. B.C. does not have disclosures.


  • Diuretics
  • Enalapril
  • Heart failure with reduced ejection fraction
  • Randomized clinical trial
  • Sacubitril/valsartan

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