Short-term Efficacy and Safety of Vasopressin Receptor Antagonists for Treatment of Hyponatremia

BACKGROUND: We performed a meta-analysis to systematically measure efficacy and safety of vasopressin receptor antagonists (VRAs) tested in randomized controlled trials for treatment of hyponatremia. METHODS: MEDLINE, ClinicalTrials. gov, and scientific abstracts were searched without language restriction. Two authors independently screened citations and extracted data on patient characteristics, quality of reports, and efficacy and safety endpoints. RESULTS: Eleven trials were identified (1094 patients). By meta-analysis, VRAs achieved a net increase in serum sodium concentration ([Na+](serum)) relative to placebo of 3.3 mEq/L at day 1 (95% confidence interval [CI], 2.7-3.8), and 4.2 mEq/L at day 2 (95% CI, 3.6-4.8), persisting at days 3-5. Larger net increases in [Na+](serum) at days 1-4 were observed in euvolemic hyponatremia and with higher doses. VRAs induced a net increase in effective water clearance relative to placebo of 1244 mL at day 1 (95% CI, 920-1567), persisting at days 2 and 4. VRAs were associated with odds ratios of 3.0 for overly rapid correction of [Na+](serum) (P <.001), 7.8 for development of hypernatremia (P <.001), 3.3 for thirst development (P <.001), and 2.2 for postural hypotension (P =.04). CONCLUSIONS: Short-term use of VRAs in treating hyponatremia was successful at raising [Na+] serum. Additional experience is required to guide their optimal use and minimize safety concerns. (C) 2011 Elsevier Inc. All rights reserved. The American Journal of Medicine (2011) 124, 977.e1-977.e9