Effects of door-to-tolvaptan time on short-term clinical outcome in patients with acute heart failure

Abstract

Aims: We investigated the effects of door-to-tolvaptan (D2T) time on short-term urine volume and in-hospital clinical outcomes in patients with acute heart failure (AHF).

Methods and results: Patients with AHF, treated with tolvaptan at two hospitals, were enrolled in this retrospective observational study. The D2T time was defined as the time elapsed from the arrival of a patient at a participating hospital to the first administration of tolvaptan. The group with the D2T time within 6 h was defined as the 'early group'. The primary outcome was 48-h urine volume. The secondary outcomes were in-hospital death, length of hospital stay, and worsening renal function (WRF) incidence. A restricted cubic spline model was used to evaluate the presence of a nonlinear association between the D2T time and 48-h urine volume and the odds ratio of WRF incidence. Our study included a total of 138 patients with AHF who were started on tolvaptan after hospitalization. The median D2T time was 5.3 h (interquartile range: 3.0-31.9 h). Seventy-four patients (53.6%) were classified to be in the early group. Baseline characteristics were similar in the two groups: mean age (85.4 ± 9.6 years vs. 84.5 ± 9.5 years; P = 0.59) and male sex (n = 22 [33.3%] vs. n = 29 [46%]; P = 0.16), except that patients in the early group had higher systolic blood pressure than those in the delayed group (138.2 ± 22.9 vs. 125.7 ± 21.7; P = 0.001). The initial tolvaptan dose in the delayed group was much lower than that in the early group (7.5 [7.5, 7.5] vs. 7.5 [5.6, 7.5] mg; P = 0.01). Total urine volume in 48 h did not differ in the early and delayed groups (4113 ± 1758 mL vs. 4201 ± 1893 mL; P = 0.80). The relationship between D2T time and total urine volume within 48 h increased slightly, with a peak at a D2T time of 15 h, and gradually decreased, thereafter. In-hospital death and the length of hospital stay did not differ significantly between the two groups (n = 1, 1.3% vs. n = 4, 6.3%; P = 0.18, and 5.0 [12.0, 30.0] vs. 22.0 [14.5, 30.0] days; P = 0.17, respectively). Notably, the restricted cubic spline model for the odds ratio of WRF incidence increased as the D2T time was delayed (P for effect<0.01).

Conclusions: The shorter D2T time did not affect the short-term urine volume and in-hospital outcomes but reduced the risk of WRF incidence in patients with AHF.

Keywords: Acute heart failure; Door-to-diuretic time; Tolvaptan; Worsening renal function.