Differential mortality association of loop diuretic dosage according to blood urea nitrogen and carbohydrate antigen 125 following a hospitalization for acute heart failure.
OBJECTIVE
Recent observations in chronic stable heart failure suggest that high-dose loop diuretics (HDLDs) have detrimental prognostic effects in patients with high blood urea nitrogen (BUN), but recent findings have also indicated that diuretics may improve renal function. Carbohydrate antigen 125 (CA125) has been shown to be a surrogate of systemic congestion. We sought to explore whether BUN and CA125 modulate the mortality risk associated with HDLDs following a hospitalization for acute heart failure (AHF).


RESULTS
We analysed 1389 consecutive patients discharged for AHF. CA125 and BUN were measured at a mean of 72 ± 12 h after admission. HDLDs (≥120 mg/day in furosemide equivalent dose) were interacted to a four-level variable according to CA125 (>35 U/mL) and BUN (above the median), and related to all-cause mortality. At a median follow-up of 21 months, 561 (40.4%) patients died. The use of HDLDs was independently associated with increased mortality [hazard ratio (HR) 1.23, 95% confidence interval (CI) 1.01-1.50], but this association was not homogeneous across CA125-BUN categories (P for interaction <0.001). In patients with normal CA125, use of HDLDs was associated with high mortality if BUN was above the median (HR 2.29, 95% 1.51-3.46), but not in those with BUN below the median (HR 1.22, 95% CI 0.73-2.04). Conversely, in patients with high CA125, HDLDs showed an association with increased survival if BUN was above the median (HR 0.73, 95% CI 0.55-0.98) but was associated with increased mortality in those with BUN below the median (HR 1.94, 95% CI 1.36-2.76).


CONCLUSIONS
The risk associated with HDLDs in patients after hospitalization for AHF was dependent on the levels of BUN and CA125. The information provided by these two biomarkers may be helpful in tailoring the dose of loop diuretics at discharge for AHF.
Servicio de Cardiología, Hospital Clínico Universitario, INCLIVA, Universitat de Valencia, 46010 Valencia, Spain. yulnunez@gmail.com
Julio
J
Núñez
Eduardo
E
Núñez
Gema
G
Miñana
Vicent
V
Bodí
Gregg C
GC
Fonarow
Vicente
V
Bertomeu-González
Patricia
P
Palau
Pilar
P
Merlos
Silvia
S
Ventura
Francisco J
FJ
Chorro
Pau
P
Llàcer
Juan
J
Sanchis
D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001806:Blood Urea Nitrogen; D018394:CA-125 Antigen / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005665:Furosemide / Q000008:administration & dosage / Q000009:adverse effects*; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy / Q000401:mortality*; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018570:Risk Assessment; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*
D015415:Biomarkers; D018394:CA-125 Antigen; D049994:Sodium Potassium Chloride Symporter Inhibitors; D005665:Furosemide