Abstract 16312: Interaction between Loop Diuretic Associated Mortality and Serum Blood Urea Nitrogen Concentration in Chronic Heart Failure: Insights from the BEST trial limited dataset
Background: Loop diuretics are commonly used to control congestive symptoms in heart failure, however, these agents cause neurohormonal activation and are associated with worsened survival. Given that blood urea nitrogen (BUN) levels increase with neurohormonal activation, we hypothesized that if the adverse effects of high dose loop diuretics are secondary to renally mediated neurohormonal activation then their association with survival may differ depending on BUN level.
Methods: Subjects in the Beta-Blocker Evaluation of Survival Trial receiving loop diuretics at baseline were analyzed (n=2456). The primary endpoint was all cause mortality.
Results: In the overall cohort, high dose loop diuretic use (>/=160 mg/day) was associated with decreased survival (HR=1.56, 95% CI 1.35 to 1.80). However, after extensively controlling for baseline characteristics, this association did not persist (HR=1.06, 95% CI 0.90 to 1.26, p=0.49). In subjects with BUN levels above the median, both the unadjusted (HR=1.59, 95% CI 1.34 to 1.88, p<0.001) and adjusted (HR=1.29, 95% CI 1.06 to 1.58, p=0.009) risk for death was higher in the group receiving high dose loop diuretics. In patients with BUN levels below the median, there was no associated risk with high dose loop diuretic use (HR=0.99, 95% CI 0.75 to 1.34, p=0.99) and after controlling for baseline characteristics, the high dose loop diuretic group had significantly improved survival (HR=0.71, 95% CI 0.51 to 0.99) (p interaction=0.007).
Conclusions: The risk associated with high dose loop diuretic use is strongly dependent on BUN concentrations with reduced survival in patients with elevated BUN and improved survival in patients with normal BUN. These data suggest a prominent role for neurohormonal activation in high dose loop diuretic associated mortality.
- © 2010 by American Heart Association, Inc.