Use of tolvaptan vs. furosemide in older patients with heart failure : Meta-analysis of randomized controlled trials

It is not known whether older patients with acute heart failure (HF) receiving tolvaptan have decreased mortality rates and a better long-term prognosis than patients who receive furosemide. We conducted a systematic review of randomized controlled trials (RCTs) to address this issue.

The Medline, Embase, and Cochrane Library databases were searched for English-language RCTs published before September 2016 comparing tolvaptan with furosemide treatment in older patients (>65 years old) after acute HF. The primary outcomes assessed were 6‑month all-cause mortality and worsening renal function (WRF); the secondary outcomes were electrolyte disorders, hospital readmissions, and adverse events.

Out of 669 citations, six RCTs met the inclusion criteria for this meta-analysis. There was a significant decrease in WRF (relative risk [RR] = 0.67, 95% confidence interval [CI] = 0.52-0.86, p = 0.002) and in the hospitalization period (mean difference [MD] = -1.86, 95% CI = -3.70--0.02, p = 0.05), as well as a significant increase in urine volume within 3 days of tolvaptan administration (MD = 1.59, 95% CI = 1.41-1.76, p < 0.00001). There were significant differences in creatinine levels between subgroups (MD = 0.33, 95% CI = 0.14-0.52, p = 0.0006). However, for the outcome of 6‑month all-cause mortality (RR = 0.56, 95% CI = 0.29-1.06, p = 0.07), there was no significant difference among all subgroups. There were significant differences in serum sodium concentration (MD = 0.68, 95% CI = 0.02-1.34, p = 0.04) but no significant changes in systolic blood pressure (MD = 3.57, 95% CI = -2.33-9.47, p = 0.24) between groups.

In older patients, tolvaptan relieves WRF, reduces the hospitalization period, and increases urine volume without significant effects on blood pressure. However, surprisingly, the use of tolvaptan did not influence 6‑month all-cause mortality.