Interaction Between Loop Diuretic-Associated Mortality and Blood Urea Nitrogen Concentration in Chronic Heart Failure

• Published in: Journal of the American College of Cardiology Vol. 58; no. 4; pp. 375 - 382
• Main Authors: Testani, Jeffrey M., Cappola, Thomas P., Brensinger, Colleen M., Shannon, Richard P., Kimmel, Stephen E.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 19.07.2011; Elsevier; Elsevier Limited
• Subjects: Aged; Beta blockers; Biological and medical sciences; Blood Urea Nitrogen; Cardiology; Cardiology. Vascular system; Cardiovascular; congestive heart failure; Diuretics; Dose-Response Relationship, Drug; Drug therapy; Female; Heart; Heart attacks; Heart Failure - blood; Heart Failure - drug therapy; Heart Failure - mortality; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Humans; Internal Medicine; kidney; loop diuretics; Male; Medical sciences; Middle Aged; Mortality; Older people; Sodium Potassium Chloride Symporter Inhibitors - adverse effects; Treatment Outcome; NYHA; kidney; GFR; NHLBI; HDLD; CI; mortality; congestive heart failure; BUN; HR; IQR; loop diuretics; glomerular filtration rate; National Heart, Lung, and Blood Institute; blood urea nitrogen; interquartile range; New York Heart Association; high-dose loop diuretic; hazard ratio; confidence interval; Heart failure; Prognosis; Interaction; Mortality; Cardiovascular disease; Nitrogen; Diuretic; Urea; Chronic; Blood concentration; Heart disease; Circulatory system; Cardiology
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2011.01.052

The purpose of this study was to investigate whether a surrogate for renal neurohormonal activation, blood urea nitrogen (BUN), could identify patients destined to experience adverse outcomes associated with the use of high-dose loop diuretics (HDLD). Loop diuretics are commonly used to control congestive symptoms in heart failure; however, these agents cause neurohormonal activation and have been associated with worsened survival. Subjects in the BEST (Beta-Blocker Evaluation of Survival Trial) receiving loop diuretics at baseline were analyzed (N = 2,456). The primary outcome was the interaction between BUN- and HDLD-associated mortality. In the overall cohort, HDLD use (≥160 mg/day) was associated with increased mortality (hazard ratio [HR]: 1.56; 95% confidence interval [CI]: 1.35 to 1.80). However, after extensively controlling for baseline characteristics, this association did not persist (HR: 1.06; 95% CI: 0.89 to 1.25). In subjects with BUN levels above the median (21.0 mg/dl), both the unadjusted (HR: 1.59; 95% CI: 1.34 to 1.88) and adjusted (HR: 1.29; 95% CI: 1.07 to 1.60) risk of death was higher in the HDLD group. In patients with BUN levels below the median, there was no associated risk with HDLD (HR: 0.99; 95% CI: 0.75 to 1.34) and after controlling for baseline characteristics, the HDLD group had significantly improved survival (HR: 0.71; 95% CI: 0.49 to 0.96) (p interaction = 0.018). The risk associated with HDLD use is strongly dependent on BUN concentrations with reduced survival in patients with an elevated BUN level and improved survival in patients with a normal BUN level. These data suggest a role for neurohormonal activation in loop diuretic–associated mortality.