Diuretic titration based on weight change in decompensated congestive heart failure: A randomized trial

doses of diuretics are related to worsening renal function (WRF), which is associated with an increase of morbidity and mortality and is a frequent complication in decompensated HF [1–9]. Clinically important increase in body weight begins at least 1 week before hospitalization for heart failure. Moreover, during this period, the risk of heart failure hospitalization increases with increasing amounts of weight gain [10]. The objective of the present study was to assess the effects of flexible diuretic titration, based on weight change, on the treatment of decompensated congestive HF. This study was carried out in the intensive Cardiology Unit in a tertiary reference university hospital. This was a prospective, randomized, single-blinded study to compare two treatment regimens of diuretics used for hospitalized patients with decompensated congestive HF: tailored (Group T) or conventional group (Group C) diuretic therapy. The primary endpoint of this study was the time to being free from congestion. The secondary endpoint was: WRF (as defined by the increase in serum creatinine N0.3 mg/dL). Patients who were eligible for screening: were ≥18 years of age, in NYHA functional class IV, ejection fraction b45% (transthoracic echocardiography), decompensated heart failure, and had the presence of two or more signs of water retention (e.g., moderate or marked edema in the lower limbs and/or sacrum, pulmonary crepitations, jugular venous pressure N10 cm, or hepatomegaly N4 cm). The exclusion criteria were: a serum urea level N150 mg/dL, serum creatinine level N3 mg/dL, peritoneal dialysis or hemodialysis, severe aortic stenosis and insulindependent diabetes mellitus. The patients were informed about the study, and if they agreed to participate, they signed the informed consent. The present study was approved by the Ethics Committee for the Analysis of the Research Project at the University of Sao Paulo. We evaluated blood tests (urea, creatinine, sodium, and potassium) every day until 24 h following congestion improvement. All the patients were followed until they were free from congestion (defined as jugular venous pressure b8 cm, a trace to no edema in the lower limbs and sacrum, no pulmonary crepitations, and hepatomegaly b 2c m). The intervention of the researcher after inclusion in the study was only correct daily dose of the diuretic in the intervention group. All the rest of the prescription, including the diuretic in the conventional group was decided by the team who attended the patient. Tailored therapy was initial dose (furosemide 120 mg/d) corrected daily by observed/expected (O/E) weight change ratio. Expected weight change was defined − 1.4%/day. If the daily weight loss was twice or more than expected, the furosemide dose was decreased by one third. If the daily weight loss was lower than expected (half or less), the furosemide dose was increased by one third. In all the other cases, the furosemide dose was maintained. The furosemide was administered until congestive signs improved. To project our needed sample size, we estimated that diuretic titration would result in a 40% reduction in the length of time to being congestion free, an alpha error of 0.05, and a power of 95%. Therefore, we required a sample size of 30 patients in both groups. For detecting associations between the diuretic treatment and the occurrence of renal failure, we used a multivariate model and a logistic regression. A p-value b 0.05 was considered significant. 34 patients were randomized to the diuretic administered according to weight evolution (titrated group), and 38 patients were randomized to the conventional group (control group). The two groups had similar baseline characteristics (Tabl e 1). The patients in the titrated group received an average dose of furosemide higher than that of the control group. The mean dose of dobutamine was similar: titrated group (6 ± 2.6 μg/kg/min vs. 7.1 ± 3.5 μg/kg/min; p =0 .2). The mean dose of furosemide in the Group T was 78.3 (29.5) mg/day vs. Group C 44.8 (23.6) mg/day p b 0.001. The mean doses of vasodilators and beta-blockers were similar in both groups.