title: A systematic review of known interventions for the treatment of chronic nonhypovolaemic hypotonic hyponatraemia and a meta-analysis of the vaptans.
abstract: International and national guidelines on the treatment of chronic nonhypovolaemic hypotonic hyponatraemia differ; therefore, we have undertaken this systematic review and meta-analysis to investigate the efficacy and safety of interventions for the treatment of chronic nonhypovolaemic hypotonic hyponatraemia. Following registration of the review protocol with PROSPERO, systematic literature searches were conducted to identify randomized and quasi-randomized controlled trials assessing any degree of fluid restriction or any drug treatment with the aim of increasing serum sodium concentration in patients with chronic nonhypovolaemic hypotonic hyponatraemia. Where appropriate, outcome data were synthesized in a meta-analysis. A total of 45 716 bibliographic records were identified from the searches and 18 trials (assessing conivaptan, lixivaptan, tolvaptan and satavaptan) met the eligibility criteria. Results suggest that all four vasopressin receptor agonists ("vaptans") significantly improve serum sodium concentration. Lixivaptan, satavaptan and tolvaptan were associated with greater rates of response versus placebo. There was no evidence of a difference between each of the vaptans compared with placebo for mortality, discontinuation and rates of hypernatraemia. No RCT evidence of treatments other than the vaptans for hyponatraemia such as oral urea, salt tablets, mannitol, loop diuretics demeclocycline or lithium was identified. Vaptans demonstrated superiority over placebo for outcomes relating to serum sodium correction. Few trials documented the potential benefit of vaptans on change in health-related quality of life as a result of treatment. There was also a lack of high-quality RCT evidence on the comparative efficacy of the vaptans and other treatment strategies for the treatment of chronic nonhypovolaemic hypotonic hyponatraemia.
authors.affiliation: Renal and Transplant Medicine, Hull and East Yorkshire Hospitals NHS Trust and Hull York Medical School (HYMS), Hull, UK.
authors.forename: Sunil
authors.initials: S
authors.lastname: Bhandari
authors.affiliation: Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Peri
authors.affiliation: Academic Department of Endocrinology and Diabetes, Queen Alexandra Hospital, Portsmouth Hospitals NHS Trust, Portsmouth, UK.
authors.forename: Iain
authors.initials: I
authors.lastname: Cranston
authors.affiliation: York Health Economics Consortium, University of York, York, UK.
authors.forename: Rachael
authors.identifier: http://orcid.org/0000-0001-6690-9952
authors.initials: R
authors.lastname: McCool
authors.affiliation: York Health Economics Consortium, University of York, York, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Shaw
authors.affiliation: York Health Economics Consortium, University of York, York, UK.
authors.forename: Julie
authors.initials: J
authors.lastname: Glanville
authors.affiliation: Otsuka Pharmaceutical Europe Ltd, Wexham, UK.
authors.forename: Larisa
authors.initials: L
authors.lastname: Petrakova
authors.affiliation: Otsuka Pharmaceutical Europe Ltd, Wexham, UK.
authors.forename: Karl
authors.initials: K
authors.lastname: O'Reilly
mesh_terms: D065092:Antidiuretic Hormone Receptor Antagonists / Q000627:therapeutic use*; D001549:Benzamides; D001552:Benzazepines; D006801:Humans; D007010:Hyponatremia / Q000628:therapy*; D009025:Morpholines; D009997:Osmotic Pressure / Q000187:drug effects; D011758:Pyrroles; D016032:Randomized Controlled Trials as Topic; D017483:Receptors, Vasopressin / Q000819:agonists*; D013141:Spiro Compounds; D000077602:Tolvaptan; D001569:Benzodiazepines
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001549:Benzamides; D001552:Benzazepines; D009025:Morpholines; D011758:Pyrroles; D017483:Receptors, Vasopressin; D013141:Spiro Compounds; D000077602:Tolvaptan; C106389:conivaptan; C409452:lixivaptan; D001569:Benzodiazepines; C103281:satavaptan