Early treatment with furosemide associated with decreased in-hospital mortality in patients with acute heart failure
EBM Focus - Volume 12, Issue 35
- Retrospective studies suggest that earlier use of vasoactive agents or diuretics is associated with decreased in-hospital mortality in patients with acute heart failure.
- In a prospective cohort study, 1,291 patients (mean age 79 years) with acute heart failure receiving furosemide IV within 24 hours of arrival at the emergency department were assessed for all-cause mortality. Treatment with furosemide within 60 minutes of arrival was compared to later treatment within 24 hours of arrival.
- Treatment with furosemide within 60 minutes of arrival was associated with decreased in-hospital mortality with death occurring in 2.3% vs. 6% with later treatment (adjusted odds ratio [OR] 0.39, 95% CI 0.2-0.76), but the decrease in 30-day mortality associated with treatment < 60 minutes did not reach statistical significance (adjusted OR 0.56, 95% CI 0.13-1).
Retrospective studies using data from the ADHERE registry suggest that in-hospital mortality is decreased with earlier use of either vasoactive or diuretic therapies in patients with acute heart failure (Congest Heart Fail 2009, J Am Coll Cardiol 2008). To prospectively evaluate the effect of time to furosemide treatment on mortality in patients with acute heart failure, a recent cohort study was conducted in 1,291 patients aged ≥ 20 years old (mean age 79 years). All patients were diagnosed with acute heart failure within 3 hours of first evaluation and treated with furosemide IV within 24 hours of arrival at the emergency department. Furosemide was given < 60 minutes after arriving at the emergency department in 481 patients and at ≥ 60 minutes after arrival in 810 patients. The main analysis was adjusted for race, age, systolic blood pressure, heart rate, blood urea nitrogen and sodium levels, and concurrence of chronic obstructive pulmonary disease (COPD). A sensitivity analysis was conducted in 708 patients propensity score-matched for arrival by ambulance, demographics, blood pressure, heart rate, signs of congestion at baseline, COPD, blood chemistry profile values, and use of an angiotensin converting enzyme inhibitor or a loop diuretic.
The median time from arrival at the emergency department to treatment with furosemide was 90 minutes. Death during hospitalization occurred in 2.3% treated with furosemide within 60 minutes of arrival vs. 6% with later treatment within 24 hours (adjusted OR 0.39, 95% CI 0.2-0.76). However, there was a nonsignificant decrease in 30-day mortality associated with treatment at < 60 minutes (adjusted OR 0.56, 95% CI 0.13-1). The event rate for this outcome was not reported. Consistent results were observed in the analysis of 708 propensity-score-matched patients.
This prospective cohort study suggests that treatment with furosemide within 60 minutes of arrival at the emergency department may decrease in-hospital mortality compared to later treatment up to 24 hours in patients with acute heart failure. The reduction in odds of death at 30 days associated with earlier treatment did not reach statistical significance, but it should be noted that the confidence interval does not exclude clinically important differences. Interpretation of the results of this study are tempered by the several baseline differences between the two groups, suggesting that there may be residual confounding even after adjustments. Potential confounders of concern include factors that increase the likelihood of early diuretic treatment and that may also select for patients who would have favorable short term responses to diuretic use on the one hand, or that may also select for patients who would be at higher risk of death on the other hand. Confounding by the former would favor the outcome in the early treatment group and the latter would favor the later treatment group. Due to ethical considerations, it is unlikely that a randomized trial delaying diuretic treatment in one group could be performed to further address this question. Future longer term and larger prospective studies accounting for potential residual confounding by indication, including factors such as respiratory rate and oxygen saturation at presentation, and cause of heart failure exacerbation, may provide a more precise estimate of survival. For now, the results from this prospective study suggest that prompt treatment with furosemide in patients with acute heart failure may improve in-hospital survival.