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Effect of tolvaptan on long-term prognosis in Japanese patients with heart failure: a systematic review and meta-analysis


 
 
 Tolvaptan (TLV), a vasopressin antagonist, can promote water diuresis and overcome various disadvantages associated with conventional diuretics by ameliorating congestive symptoms and improving hyponatremia while maintaining haemodynamics and renal function. Large-scale clinical trials conducted primarily in Western countries (e.g. EVEREST trial) failed to demonstrate the beneficial effect of TLV on prognosis in patients with heart failure (HF). However, even after these clinical trials, studies on the use of TLV add-on therapy and resultant prognosis have been reported in Asian countries. Racial differences can greatly affect drug efficacy and dosing.
 
 
 
 We sought to investigate the long-term prognostic effect of TLV add-on therapy in Asian patients with HF.
 
 
 
 We searched MEDLINE, Scopus, Cochrane Central, and Google Scholar for articles published till 31 December 2019. Randomized controlled trials (RCTs) and matched case-control studies that had a follow-up period of at least 6 months and that compared TLV add-on therapy and conventional therapy (control group) in Asian patients with acute decompensated HF were included. Primary and secondary outcomes analysed were all-cause mortality and HF readmission, respectively. Pooled analysis was performed using univariate effect size with random effect models. Meta-regression was performed to assess the impact of potential covariates.
 
 
 
 Nine articles that enrolled 1010 patients (the range of patients in the enrolled studies: 58–217) were included in the systematic review. All studies were performed in Japan. The weighted mean follow-up period was 15 months. The weighted mean of sodium level and ejection fraction was 139 mEq/L and 47%, respectively. TLV dose at discharge was available only in five articles, and its weighted mean value was 8.8 mg/day. In the pooled analysis, TLV add-on therapy did not improve the incidence of all-cause mortality (OR: 1.02, 95% CI: 0.69–1.52, p=0.92, I2=23) and HF readmission (OR: 0.73, 95% CI: 0.24–2.22, p=0.58, I2=89) (Figure). Furthermore, the effect of TLV add-on therapy on all-cause mortality was significantly moderated by furosemide dose at discharge in the control group (p=0.03).
 
 
 
 Similar to findings of previous RCTs completed in Western countries, we found that TLV add-on therapy did not improve long-term mortality and HF readmission in Japanese patients with HF; however, mostly small-scale studies were included in our review. TLV add-on therapy might contribute to the improvement in prognosis in HF patients taking large doses of furosemide.
 Forest plot of tolvaptan's effect
 
 
 
 Type of funding source: Private hospital(s). Main funding source(s): Kitaishikai
