Higher doses of loop diuretics limit uptitration of angiotensin converting enzyme inhibitors in patients with heart failure and reduced ejection fraction

Jozine M. ter Maaten, Pieter Martens, Kevin Damman, Kenneth Dickstein, Piotr Ponikowski, Chim Lang, Leong Loke Ng, Stefan D. Anker, Nilesh J. Samani, Gerasimos S. Filippatos, John G. F. Cleland, Faiez Zannad, Hans L. Hillege, Dirk Jan van Veldhuisen, Marco Metra, Adriaan A. Voors (Lead / Corresponding author), Wilfried Mullens

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Abstract

Background: Loop diuretics are frequently prescribed to patients with heart failure and reduced ejection fraction (HFrEF) for the treatment of congestion; however, they might hamper uptitration of inhibitors of the renin–angiotensin system.

Methods: Loop diuretic dose at baseline was recorded in 2338 patients with HFrEF enrolled in BIOSTAT-CHF, an international study of HF patients on loop diuretic therapy who were eligible for uptitration of angiotensin-converting enzyme inhibitors (ACEi)/mineralocorticoid receptor antagonists (MRA). The association between loop diuretic dose and uptitration of ACEi/MRA to percentage of target dose was adjusted for a previously published model for likelihood of uptitration and a propensity score.

Results: Baseline median loop diuretic dose was 40 [40–100] mg of furosemide or equivalent. Higher doses of loop diuretics were associated with higher NYHA class and higher levels of NT-proBNP, more severe signs and symptoms of congestion, more frequent MRA use, and lower doses of ACEi reached at 3 and 9 months (all P < 0.01). After propensity adjustment, higher doses of loop diuretics remained significantly associated with poorer uptitration of ACEi (Beta per log doubling of loop diuretic dose: − 1.66, P = 0.021), but not with uptitration of MRAs (P = 0.758). Higher doses of loop diuretics were independently associated with an increased risk of all-cause mortality or HF hospitalization [HR per doubling of loop diuretic dose: 1.06 (1.01–1.12), P = 0.021].

Conclusions: Higher doses of loop diuretics limited uptitration of ACEi in patients with HFrEF and were associated with a higher risk of death and/or HF hospitalization, independent of their lower likelihood of uptitration and higher baseline risk.

Original languageEnglish
Number of pages12
JournalClinical Research in Cardiology
Early online date30 Jan 2020
DOIs
Publication statusE-pub ahead of print - 30 Jan 2020

Keywords

  • ACEi/ARB
  • Guideline recommended treatment
  • Heart failure
  • Loop diuretics

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    ter Maaten, J. M., Martens, P., Damman, K., Dickstein, K., Ponikowski, P., Lang, C., Ng, L. L., Anker, S. D., Samani, N. J., Filippatos, G. S., Cleland, J. G. F., Zannad, F., Hillege, H. L., van Veldhuisen, D. J., Metra, M., Voors, A. A., & Mullens, W. (2020). Higher doses of loop diuretics limit uptitration of angiotensin converting enzyme inhibitors in patients with heart failure and reduced ejection fraction. Clinical Research in Cardiology . https://doi.org/10.1007/s00392-020-01598-w