Heart failure
Relation of Loop Diuretic Dose to Mortality in Advanced Heart Failure

https://doi.org/10.1016/j.amjcard.2005.12.072Get rights and content

Although loop diuretics are widely used in heart failure (HF), their effect on outcomes has not been evaluated in large clinical trials. This study sought to determine the dose-dependent relation between loop diuretic use and HF prognosis. A cohort of 1,354 patients with advanced systolic HF referred to a single center was studied. Patients were divided into quartiles of equivalent total daily loop diuretic dose: 0 to 40, 41 to 80, 81 to 160, and >160 mg. The cohort was 76% male, with a mean age of 53 ± 13 years and a mean ejection fraction of 24 ± 7%. The mean diuretic dose equivalence was 107 ± 87 mg. The diuretic quartile groups were similar in terms of gender, body mass index, ischemic cause of HF, history of hypertension, and spironolactone use, but the highest quartile was associated with a smaller ejection fraction and lower serum sodium and hemoglobin levels but higher serum blood urea nitrogen and creatinine levels. There was a decrease in survival with increasing diuretic dose (83%, 81%, 68%, and 53% for quartiles 1, 2, 3, and 4, respectively). Even after extensive co-variate adjustment (age, gender, ischemic cause of HF, the ejection fraction, body mass index, pulmonary capillary wedge pressure, peak oxygen consumption, β-blocker use, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, digoxin use, statin use, serum sodium, blood urea nitrogen, creatinine, hemoglobin, cholesterol, systolic blood pressure, and smoking history), diuretic quartile remained an independent predictor of mortality (quartile 4 vs quartile 1 hazard ratio 4.0, 95% confidence interval 1.9 to 8.4). In conclusion, in this cohort of patients with advanced HF, there was an independent, dose-dependent association between loop diuretic use and impaired survival. Higher loop diuretic dosages identify patients with HF at particularly high risk for mortality.

Section snippets

Patient population

The study population consisted of 1,354 consecutive patients with advanced systolic HF referred to a single university medical center for HF management and/or transplant evaluation from 1985 to 2004. Patients with left ventricular ejection fractions >40%, those with HF due to valvular disease, and those aged <18 years were excluded from the analysis. All patients were followed in a comprehensive HF management program, as previously described.4 This study was approved by the University of

Baseline characteristics of the cohort

The cohort was 76% male and ranged in age from 18 to 84 years (mean 53 ± 13). New York Heart Association class III and IV HF constituted 39% and 47% of the population, respectively. The mean left ventricular ejection fraction was 24 ± 7% (Table 1). Causes of HF were ischemic (47%) and idiopathic (33%); the remaining causes included alcohol induced, hypertrophic, and postpartum cardiomyopathy.

Diuretic dose and patient characteristics

There were 465 patients (34%) in the first quartile, with dose equivalence of 0 to 40 mg; 365 patients

Discussion

This study suggests that in patients with advanced systolic HF, the use of higher doses of loop diuretics is associated with significantly increased all-cause mortality. We observed that the highest diuretic doses (>160 mg) were associated with a significant increase in 1- and 2-year all-cause mortality compared with the lowest loop diuretic doses (0 to 40 mg). The association was not limited to the mode of death; death from any cause, death and urgent transplantation, progressive HF death, and

References (25)

  • M. Packer et al.

    The effect of carvedilol on morbidity and mortality in patients with chronic heart failure

    N Engl J Med

    (1996)
  • B. Pitt et al.

    The effect of spironolactone on morbidity and mortality in patients with severe heart failure

    N Engl J Med

    (1999)
  • Cited by (337)

    View all citing articles on Scopus

    This research was supported by the Ahmanson Foundation, Los Angeles, California. Dr. Horwich was supported by Training Grant 401357JI30608 from the National Institutes of Health, Bethesda, Maryland.

    View full text