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.
Central Illustration
Key Words
ATMOSPHERE
diuretic initiation
diuretic medications
heart failure
PARADIGM-HF
Abbreviations and Acronyms
AF
atrial fibrillation
BMI
body mass index
eGFR
estimated glomerular filtration rate
HF
heart failure
HFrEF
heart failure with reduced ejection fraction
KCCQ-CSS
Kansas City Cardiomyopathy Questionnaire Clinical Summary Score
LVEF
left ventricular ejection fraction
MRA
mineralocorticoid receptor antagonist
NT-proBNP
N-terminal pro–B-type natriuretic peptide
NYHA
New York Heart Association
RAAS
renin-angiotensin-aldosterone system
SBP
systolic blood pressure
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