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Aims We studied the characteristics and clinical outcome related to diuretic response and the effects of serelaxin in patients
hospitalized for acute heart failure (AHF).

Methods
and results
RELAX-AHF was a double-blind, placebo-controlled trial, enrolling 1161 patients admitted to hospital for AHF who
were randomized to 48 h i.v infusions of placebo or serelaxin (30 μg/kg per day) within 16 h from presentation.
Diuretic response was defined as Δ weight kg/[(total i.v. dose)/40mg]+[(total oral dose)/80mg)] furosemide (or
equivalent loop diuretic dose) up to day 5. Median diuretic response was −0.42 (−1.00, −0.14) kg/40mg. A poor
diuretic response was independently associated with Western-like region (Western Europe, North America, Israel,
and Poland), lower diastolic blood pressure, the absence of oedema, higher blood urea nitrogen, and lower levels
of aspartate aminotransferase and potassium (all P <0.01). Randomization to serelaxin was associated with lower
doses of i.v. loop diuretics and slightly less weight loss, resulting in a neutral effect on diuretic response. Worse
diuretic response was independently associated both with less relief of dyspnoea, measured with a visual analogue
scale (VAS) at day 5 (primary endpoint; P =0.0002), and with a higher risk of cardiovascular death or rehospitalization
for heart failure or renal failure through day 60 (secondary endpoint, P <0.0001), but not with increased 180-day
cardiovascular mortality (P =0.507).

Conclusions In patients hospitalized for AHF, a poor diuretic response was associated with a poor in-hospital and early
post-discharge clinical outcome. Serelaxin had a neutral effect on diuretic response.

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Background
Loop diuretics are an essential component of therapy for patients with acute decompensated
heart failure, but there are few prospective data to guide their use.
Methods
In a prospective, double-blind, randomized trial, we assigned 308 patients with acute
decompensated heart failure to receive furosemide administered intravenously by
means of either a bolus every 12 hours or continuous infusion and at either a low
dose (equivalent to the patient’s previous oral dose) or a high dose (2.5 times the previous
oral dose). The protocol allowed specified dose adjustments after 48 hours. The
coprimary end points were patients’ global assessment of symptoms, quantified as
the area under the curve (AUC) of the score on a visual-analogue scale over the course
of 72 hours, and the change in the serum creatinine level from baseline to 72 hours.
Results
In the comparison of bolus with continuous infusion, there was no significant difference
in patients’ global assessment of symptoms (mean AUC, 4236±1440 and
4373±1404, respectively; P = 0.47) or in the mean change in the creatinine level
(0.05±0.3 mg per deciliter [4.4±26.5 μmol per liter] and 0.07±0.3 mg per deciliter
[6.2±26.5 μmol per liter], respectively; P = 0.45). In the comparison of the high-dose
strategy with the low-dose strategy, there was a nonsignificant trend toward greater
improvement in patients’ global assessment of symptoms in the high-dose group
(mean AUC, 4430±1401 vs. 4171±1436; P = 0.06). There was no significant difference
between these groups in the mean change in the creatinine level (0.08±0.3 mg
per deciliter [7.1±26.5 μmol per liter] with the high-dose strategy and 0.04±0.3 mg per
deciliter [3.5±26.5 μmol per liter] with the low-dose strategy, P = 0.21). The high-dose
strategy was associated with greater diuresis and more favorable outcomes in some
secondary measures but also with transient worsening of renal function.
Conclusions
Among patients with acute decompensated heart failure, there were no significant
differences in patients’ global assessment of symptoms or in the change in renal
function when diuretic therapy was administered by bolus as compared with continuous
infusion or at a high dose as compared with a low dose. (Funded by the
National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00577135.)

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