The short-term and long-term effects of tolvaptan in patients with heart failure: a meta-analysis of randomized controlled trials

Abstract

A comprehensive evaluation of the benefits of tolvaptan for the management of heart failure (HF) is lacking. The objective of this meta-analysis was to assess the short-term and long-term effects of tolvaptan in patients with HF. Articles were searched from PubMed, MEDLINE and Cochrane Library before March 31, 2015. Randomized controlled trials enrolling adult HF patients and reporting the all-cause mortality, cardiac events, body weight change or changes of serum electrolytes including sodium, potassium and creatinine were included in our meta-analysis. Ten studies covering 5574 patients met the inclusion criteria. Based on the data of meta-analysis, tolvaptan had no impact on the all-cause mortality [relative risk (RR) 0.96; 95 % confidence interval (CI) 0.87-1.06; P = 0.40] and incidence of cardiac events (RR 1.03; 95 % CI 0.96-1.11; P = 0.40) of HF patients. Furthermore, in comparison with control treatments, tolvaptan significantly decreased the body weight [weight mean difference (WMD), -0.87; 95 % CI -1.03 to -0.71; P < 0.001] and statistically increased serum sodium (WMD, 2.58; 95 % CI -1.83 to 3.33; P < 0.001) without any change in serum potassium (WMD, 0.01; 95 % CI -0.03 to 0.05; P = 0.577). However, serum creatinine may be increased slightly by tolvaptan (WMD, 0.05; 95 % CI 0.03-0.07; P < 0.001). This meta-analysis suggests that in HF patients, tolvaptan may not bring long-term benefits, but it effectively improves the volume overload and hyponatremia without obvious increases in serum potassium and creatinine. Hence, tolvaptan is likely to be a promising diuretic for the treatment of HF.

Effects of Tolvaptan in patients with acute heart failure: a systematic review and meta-analysis

“…A previous meta-analysis showed that TLV elevated the serum creatinine level slightly [11]; however, there was no significant difference in morbidity associated with renal dysfunction between TLV and control groups in EVEREST study [26]. The changes in creatinine levels that occur during successful decongestion therapy do not necessarily indicate the same adverse prognosis [27].…”

“…Previous studies have shown that TLV is a safe and effective drug for the treatment of euvolemic and hypervolemic hyponatremia as well as for patients with HF [9, 10]. Three meta-analyses were performed to investigate the efficacy and safety of TLV treatment in patients hospitalised for HF [11–13]; however, these analyses were primarily focused on chronic heart failure (CHF). Since the publication of these meta-analyses, many new clinical trials have been performed to investigate the efficacy and safety of TVL in patients with AHF [8, 14, 15].…”

Effects of Tolvaptan on Volume Overload in Patients with Heart Failure

“…Our findings of significant changes (decrease in body weight, increase in urine volume, and increase in serum sodium level) with add-on tolvaptan therapy support the results of previous meta-analyses. [10][11][12][13] Alkaf, et al 12) analyzed seven double-blind RCTs and found that tolvaptan had no effect on all-cause mortality, but its body weight, urine volume, and serum sodium level improved significantly. Xiong, et al 10) integrated 10 RCTs and found that there was no long-term benefit of tolvaptan, but body weight, urine volume, and serum sodium level improved significantly.…”

“…Since 2015, meta-analyses of tolvaptan have been reported. [10][11][12][13][14] In recent years, several randomized controlled trials (RCTs) performed in actual clinical settings in Japan have also been reported, calling attention to the need for integrated analysis of differences between the doses of tolvaptan used in previous clinical studies in Europe and North America and the doses currently used in Japan. We performed a meta-analysis of RCTs in Europe, North America, and Japan.…”

Experience with long-term administration of tolvaptan to patients with acute decompensated heart failure

“…Moreover, the package insert also recommends not administering TLV over a prolonged period if fluid retention disappears and/or body weight is within the target range. However, a study has revealed that some patients require TLV over a prolonged period (4). In addition, the long-term use of TLV is reported to reduce the dosage of loop diuretics (5).…”