While loop diuretics are an acknowledged component of therapy for patients with acute decompensated heart failure, as they were introduced into clinical practice prior to the era of large randomised controlled trials there are few prospective data to guide their use.
To better define the most pertinent strategy for their use, the authors conducted a prospective, double-blind, randomized trial, in which 308 patients with acute decompensated heart failure were assigned to receive furosemide administered intravenously by means of either a bolus every 12 hours or continuous infusion at either a low dose (equivalent to the patient’s previous oral dose) or a high dose (2.5 times the previous oral dose). Any patients requiring inotropes or vasodilators were excluded. The co-primary end points were patients’ global assessment of symptoms using a visual-analogue scale, and the change in the serum creatinine level from baseline to 72 hours.
While previous smaller trials of similar design have generally favoured a continuous infusion strategy, in the comparison of bolus with continuous infusion there was no significant difference in patients’ assessment of symptoms (mean AUC, 4236±1440 and 4373±1404, respectively; P=0.47) or in the mean change in creatinine (4.4±26.5 μmol/l and 6.2±26.5 μmol/l, respectively; P=0.45). In the comparison of the high-dose strategy with the low-dose strategy, there was a trend toward greater improvement in patients’ symptoms with the high-dose (mean AUC, 4430±1401 vs. 4171±1436; P=0.06), while there was no significant difference in change in creatinine (7.1±26.5 μmol/l with the high-dose and 3.5±26.5 μmol/l with the low-dose, P=0.21). The high-dose strategy was associated with greater diuresis and more favourable outcomes in some secondary measures but also with transient worsening of renal function and none of the strategies showed any benefit in reducing length of hospital stay or 60 day survival or re-hospitalisation rates.
Conclusions
In the largest trial of its kind to date, among patients with acute decompensated heart failure there were no significant differences either in efficacy or safety when diuretic therapy was administered by bolus as compared with continuous infusion, nor at a high dose as compared with a low dose.
- Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, LeWinter MM, Deswal A, Rouleau JL, Ofili EO, Anstrom KJ, Hernandez AF, McNulty SE, Velazquez EJ, Kfoury AG, Chen HH, Givertz MM, Semigran MJ, Bart BA, Mascette AM, Braunwald E, O’Connor CM; NHLBI Heart Failure Clinical Research Network. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011 Mar 3;364(9):797-805.