Timing of Worsening Renal Function in Patients Hospitalized for Heart Failure Exacerbation Who Were Being Treated With Intravenous Diuretic Therapy.

BACKGROUND: This retrospective observational study investigated the incidence of worsening renal function (WRF) in patients hospitalized for heart failure (HF) and treated with intravenous diuretics in Japan.Methods and Results: Associations between WRF at any point and HF treatments, and the effects of WRF on outcomes were evaluated (Diagnosis Procedure Combination database). Of 1,788 patients analyzed (mean [±SD] age 80.5±10.2 years; 54.4% male), 641 (35.9%) had WRF during a course of hospitalization for worsening HF: 208 (32.4%) presented with WRF before admission (BA-WRF; estimated glomerular filtration rate decreased by ≥25% from baseline at least once between 30 days prior to admission and admission); 44 (6.9%) had WRF that persisted before and after admission (P-WRF); and 389 (60.7%) had WRF develop after admission (AA-WRF). Delayed initial diuretic administration, higher maximum doses of intravenous diuretics during hospitalization, and diuretic readministration during hospitalization were associated with a significantly higher incidence of AA-WRF. Patients with WRF at any time point were at higher risk of death during hospitalization compared with patients without WRF, with adjusted hazard ratios of 3.56 (95% confidence interval [CI] 2.23-5.69) for BA-WRF, 3.23 (95% CI 2.21-4.71) for AA-WRF, and 13.16 (95% CI 8.19-21.15) for P-WRF (all P<0.0001). CONCLUSIONS: Forty percent of WRF occurred before admission for acute HF; there was no difference in mortality between patients with BA-WRF and AA-WRF.

Real-World Intravenous Diuretic Use to Treat Congestion in Patients With Heart Failure　- An Observational Study Using a Research Database.

Background: Intravenous (IV) diuretics are key in the treatment of acute heart failure, but the time of administration can affect outcomes. Using a medical database, we assessed the real-world usage and clinical impact of IV diuretics after admission. Methods and Results: This observational study included hospitalized patients with heart failure who received IV diuretics. Relationships between IV diuretic use and clinical outcomes (duration of hospitalization, in-hospital mortality, readmission) were evaluated using analysis of variance or logistic regression. Overall, 9,653 patients (51.1% male) were assessed (mean age 80.9 years). Most (89.1%) patients had IV loop diuretic treatment initiated on Day 1 of hospitalization and 68.0% achieved the maximum dose on that day. The median duration of hospitalization was 17.0 days. In-hospital mortality was 9.2%; 13.7% of patients were readmitted within 3 months after discharge. There were prognostic relationships between IV diuretic usage and both duration of hospitalization and in-hospital mortality. On multivariable analysis, the time of maximum dose had the biggest impact on outcomes. Duration of hospitalization was prolonged and in-hospital mortality rates increased when the time of maximum dose was delayed. There was little correlation between IV diuretic use and readmission following discharge. Conclusions: Short-term outcomes (duration of hospitalization, in-hospital mortality) correlated with the time of maximum IV diuretic dose; thus, early initiation and subsequent modification of appropriate congestion treatment is critical for prognostic improvement.

Efficacy and safety of intravenous OPC-61815 compared with oral tolvaptan in patients with congestive heart failure.

AIMS: This multicentre, randomized, controlled, double-blind, parallel-group Phase III study was conducted to confirm the non-inferiority of OPC-61815 (tolvaptan sodium phosphate) intravenous injections to oral tolvaptan tablets in patients with congestive heart failure and volume overload despite receiving diuretics other than vasopressin antagonists. METHODS AND RESULTS: Congestive heart failure patients with volume overload despite receiving diuretics other than vasopressin antagonists were randomly assigned (1:1) to receive OPC-61815 (16-mg injection; n = 149) or oral tolvaptan (15-mg tablet; n = 145) once daily for 5 days. Most patients were male; the mean age and weight were 74.7 years and 62.1 kg, respectively; other demographic and clinical characteristics were similar between groups. In this study, the primary endpoint was the change in body weight from baseline to the day after the last dose. Secondary endpoints included improvement from baseline in congestive findings and New York Heart Association classification. The change in body weight was -1.67 kg [95% confidence interval (CI): -1.93, -1.41] and -1.36 kg (95% CI: -1.62, -1.10) in the OPC-61815 group and tolvaptan group, respectively; the difference in the least squares mean between the groups was -0.31 kg (95% CI: -0.68, 0.06). Given the upper CI did not exceed the pre-specified limit of 0.48, this confirmed the non-inferiority of injectable OPC-61815 to oral tolvaptan. Daily urine volume and daily fluid intake increased, and daily fluid balance was negative throughout the treatment period; changes were similar for both groups. All evaluated congestive symptoms and New York Heart Association classifications showed improvement and safety findings were similar between the groups. The incidence of hyperkalaemia was higher in the OPC-61815 group, and the incidence of thirst and dry mouth was higher in the tolvaptan group. Most treatment-emergent adverse events were mild to moderate; one serious treatment-emergent adverse event of hyperkalaemia in the OPC-61815 group was considered treatment related. CONCLUSIONS: OPC-61815 (16-mg injection) was confirmed as non-inferior to oral tolvaptan (15-mg tablet) in patients with congestive heart failure and inadequate response to diuretics; no new safety concerns were observed.