Kogure Tomohito, Jujo Kentaro, Hamada Kazuyuki, Saito Katsumi, Hagiwara Nobuhisa
Department of Cardiology, Tokyo Women's Medical University, 8-1 Kawadacho, Shinjuku-ku, Tokyo, 162-0054, Japan.
Department of Cardiology, Nishiarai Heart Center Hospital, Tokyo, Japan.
Heart Vessels. 2018 Apr;33(4):374-383. doi: 10.1007/s00380-017-1072-6. Epub 2017 Nov 11.
Tolvaptan has been gradually spread to use as a potent diuretic for congestive heart failure in the limited country. However, the response to this aquaretic drug still is unpredictable. A total of 92 patients urgently hospitalized due to congestive heart failure and treated with tolvaptan in addition to standard treatment was retrospectively analyzed. Responder of tolvaptan treatment was defined as a patient with peak negative fluid balance greater than 500 mL/day, and clinical profiles were compared between 76 responders and 16 non-responders. Responders started to increase daily urine volume (UV) from Day 1 through Day 3. In contrast, non-responders showed no significant increase in daily UV from the baseline up to Day 5. Time between admission and tolvaptan administration was shorter in responders, even without statistical significance (3.3 vs. 4.6 days, p = 0.053). Multivariate analysis revealed that blood urea nitrogen (BUN) [cutoff: 34 mg/dL, odds ratio (OR) 9.0, 95% confidence interval (CI) 1.42-57.3, p < 0.01] and plasma renin activity (PRA) (cutoff: 4.7 ng/mL/h, OR 6.1, 95% CI 1.01-36.4, p < 0.01) at baseline were independent predictors for tolvaptan responsiveness. It suggests that renal perfusion may affect tolvaptan-induced UV. Finally, durations of stay in intensive care unit and total hospitalization were significantly shorter in responders (median: 6.0 vs. 13.0 days, p = 0.022; 15.0 vs. 25.0 days, p = 0.016, respectively). Responders of tolvaptan have lower BUN and renin activity at baseline, and shorten hospitalization period. Trial Registration The study was registered at University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) with the identifier UMIN000023594. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000024988.
在一些有限的国家，托伐普坦已逐渐被广泛用作治疗充血性心力衰竭的强效利尿剂。然而，这种排水利尿药物的疗效仍然难以预测。我们对92例因充血性心力衰竭紧急住院且在标准治疗基础上加用托伐普坦治疗的患者进行了回顾性分析。托伐普坦治疗的有效者定义为每日液体负平衡峰值大于500 mL/天的患者，并比较了76例有效者和16例无效者的临床特征。有效者从第1天到第3天每日尿量（UV）开始增加。相比之下，无效者从基线到第5天每日UV无显著增加。有效者入院至使用托伐普坦的时间较短，尽管无统计学意义（3.3天对4.6天，p = 0.053）。多因素分析显示，基线时血尿素氮（BUN）[临界值：34 mg/dL，比值比（OR）9.0，95%置信区间（CI）1.42 - 57.3，p < 0.01]和血浆肾素活性（PRA）（临界值：4.7 ng/mL/h，OR 6.1，95%CI 1.01 - 36.4，p < 0.01）是托伐普坦反应性的独立预测因素。这表明肾灌注可能影响托伐普坦诱导的UV。最后，有效者在重症监护病房的住院时间和总住院时间显著缩短（中位数：分别为6.0天对13.0天，p = 0.022；15.0天对25.0天，p = 0.016）。托伐普坦有效者基线时BUN和肾素活性较低，且住院时间缩短。试验注册 本研究在大学医院医学信息网络临床试验注册中心（UMIN - CTR）注册，标识符为UMIN000023594。https://upload.umin.ac.jp/cgi - open - bin/ctr_e/ctr_view.cgi?recptno=R000024988 。
