Clinical Outcomes Related to Background Diuretic Use and New Diuretic Initiation in Patients With HFrEF

JACC Heart Fail. 2022 Jun;10(6):415-427. doi: 10.1016/j.jchf.2022.01.020. Epub 2022 Apr 6.

Abstract

Background: Up to 20% of patients in heart failure with reduced ejection fraction (HFrEF) trials are not taking diuretic agents at baseline, but little is known about them.

Objectives: The aim of this study was to examine outcomes in patients with HFrEF not taking diuretic medications and after diuretic medications are started.

Methods: Patient characteristics and outcomes were compared between patients taking or not taking diuretic drugs at baseline in the ATMOSPHERE (Aliskiren Trial of Minimizing Outcomes for Patients With Heart Failure) and PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial) trials combined. Patients starting diuretic medications were also compared with those remaining off diuretic drugs during follow-up. Symptoms (Kansas City Cardiomyopathy Questionnaire Clinical Summary Score [KCCQ-CSS]), hospitalization for worsening heart failure (HF), mortality, and kidney function (estimated glomerular filtration rate slope) were examined.

Results: At baseline, the 3,079 of 15,415 patients (20%) not taking diuretic medications had a less severe HF profile, less neurohumoral activation, and better kidney function. They were less likely to experience the primary outcome (hospitalization for HF or cardiovascular death) than patients taking diuretic agents (adjusted HR: 0.77; 95% CI: 0.74-0.80; P < 0.001) and death of any cause. Commencement of a diuretic drug was associated with higher subsequent risk for death (adjusted HR: 2.05; 95% CI: 1.99-2.11; P < 0.001) and greater decreases in KCCQ-CSS and estimated glomerular filtration rate. The 5 strongest predictors of initiation of diuretic medications were higher N-terminal pro-B-type natriuretic peptide, higher body mass index, older age, history of diabetes, and worse KCCQ-CSS. In PARADIGM-HF, fewer patients who were treated with sacubitril/valsartan commenced diuretic agents (OR: 0.72; 95% CI: 0.58-0.88; P = 0.002).

Conclusions: Patients with HFrEF not taking diuretic medications and those who remained off them had better outcomes than patients treated with diuretic agents or who commenced them.

Keywords: ATMOSPHERE; PARADIGM-HF; diuretic initiation; diuretic medications; heart failure.

MeSH terms

  • Aminobutyrates
  • Angiotensin Receptor Antagonists / therapeutic use
  • Biphenyl Compounds
  • Diuretics / therapeutic use
  • Heart Failure* / drug therapy
  • Humans
  • Prospective Studies
  • Stroke Volume / physiology
  • Tetrazoles / therapeutic use
  • Ventricular Dysfunction, Left*

Substances

  • Aminobutyrates
  • Angiotensin Receptor Antagonists
  • Biphenyl Compounds
  • Diuretics
  • Tetrazoles
  • sacubitril