著者
Koichiro Kinugawa Naoki Sato Takayuki Inomata Moriyoshi Yasuda Yoshiyuki Shibasaki Toshiyuki Shimakawa
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.82, no.5, pp.1344-1350, 2018-04-25 (Released:2018-04-25)
参考文献数
16
被引用文献数
13 19

Background:It has been 7 years since tolvaptan was approved in Japan for the indication of heart failure in patients with volume overload; the drug can be used in patients with normonatremia. Hypernatremia was identified as a significant adverse event to be prevented.Methods and Results:We compiled and analyzed data from 3,349 patients over 5 years to identify patients at high risk of hypernatremia with tolvaptan treatment. The incidence of hypernatremia, defined as serum sodium ≥150 mEq/L, was 3.65%. Baseline serum sodium concentrations, serum potassium concentrations, blood urea nitrogen : creatinine ratio, initial tolvaptan dose, and age were identified as risk factors for hypernatremia. A hypernatremia risk score was developed using the odds ratios for these factors. The high-risk population was defined as patients with a risk score ≥17.80.Conclusions:To prevent the occurrence of hypernatremic events in patients taking tolvaptan, we recommend a very low starting dose (i.e., 3.75 mg/day) in patients identified as being at high risk of hypernatremia using our new scoring process.
著者
Koichiro Kinugawa Naoki Sato Takayuki Inomata Moriyoshi Yasuda Toshiyuki Shimakawa Yasuhiko Fukuta
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-19-0158, (Released:2019-05-22)
参考文献数
26
被引用文献数
19

Background:In Japan, tolvaptan is indicated for patients with heart failure and volume overload who have inadequate response to other diuretics. In contrast to the USA and Europe, tolvaptan can be used in Japan in patients with normal sodium levels.Methods and Results:In this multicenter, non-interventional, post-marketing surveillance study, prospective data from 3,349 patients treated with tolvaptan over a 5-year period were analyzed to identify benefits and risks. By Day 2 of treatment, 76.9% of evaluable patients had an increase in baseline 24-h urine volume (tolvaptan responders). Mean change in body weight was similar between 7.5 mg and 15 mg dosage groups (−3.6±3.9 kg and −3.7±4.0 kg, respectively). Improvement or disappearance rates for congestive symptoms from baseline to Day 14 ranged from 77.7% for lower limb edema to 51.1% for 3rd sound. Adverse drug reactions were reported in 18.1% of patients, most frequently thirst (8.4%). No case of central pontine myelinolysis was reported. All-cause mortality was significantly lower in patients with improved sodium concentration and increased 24-h urine volume.Conclusions:The effectiveness and safety of tolvaptan in real-world clinical settings was confirmed in this large-scale analysis. The 7.5-mg dose was equally as effective as the 15-mg dose and had a better safety profile. Improvements in all-cause mortality were suggested in tolvaptan responders.