title: Vasopressin receptor antagonists for the treatment of heart failure: a systematic review and meta-analysis of randomized controlled trials.
abstract: OBJECTIVE
  Elevated vasopressin may increase systemic vascular resistance and pulmonary capillary wedge pressure, subsequently decrease stroke volume and cardiac output. Vasopressin receptor antagonists may counteract these effects and improve outcomes in heart failure. We aimed to assess benefits and harms of vasopressin receptor antagonists (VRAs) versus placebo in addition to standard care in adults with heart failure (HF).
  
  
  METHODS
  We conducted a systematic review of randomized controlled trials with searches of CENTRAL and MEDLINE to January 2014 and reference lists without language restriction. Meta-analysis using a random-effects model was done for all-cause and cardiovascular mortality, hospitalization for heart failure, changes in clinical assessment of HF, serum sodium concentration (Na), kidney function and treatment-specific side effects.
  
  
  RESULTS
  We identified 13 trials and 5,525 participants. In 10 trials, participants received standard therapy for HF. In low-quality evidence, VRAs in patients with HF had no effect on all-cause mortality risk ratios (RR 0.98; CI 0.88-1.08), cardiovascular mortality (RR 1.03; CI 0.91-1.16) or change in creatinine mean difference (MD -0.01; CI -0.10 to 0.09 mg/dL), but reduced body weight by 0.8 kg from baseline (MD -0.83; CI -1.10 to -0.55 kg) and increased Na (MD 2.61; 95 % CI 1.88-3.35 mmol/L). Compared with placebo, VRAs increased the risk of adverse events by 14 % (RR 1.14; CI 1.04-1.26). Studies were generally limited to short-term follow-up with limited data available on patient important outcomes.
  
  
  CONCLUSIONS
  Vasopressin receptors antagonists may reduce body weight and increase Na but do not improve all-cause mortality, cardiovascular mortality or kidney function. In addition, acceptability of long-term treatment side effects and hospitalization appears problematic.
authors.affiliation: Nephrology Department, University Hospital "Dr. C.I. Parhon", Iasi, Romania, ionutni@yahoo.com.
authors.forename: Ionut
authors.initials: I
authors.lastname: Nistor
authors.forename: Iris
authors.initials: I
authors.lastname: Bararu
authors.forename: Maria-Cristina
authors.initials: MC
authors.lastname: Apavaloaie
authors.forename: Luminita
authors.initials: L
authors.lastname: Voroneanu
authors.forename: Mihaela-Dora
authors.initials: MD
authors.lastname: Donciu
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kanbay
authors.forename: Evi V
authors.initials: EV
authors.lastname: Nagler
authors.forename: Adrian
authors.initials: A
authors.lastname: Covic
mesh_terms: D065092:Antidiuretic Hormone Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D002423:Cause of Death; D003404:Creatinine / Q000097:blood; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012964:Sodium / Q000097:blood
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D012964:Sodium; D003404:Creatinine