Vasopressin Antagonists: Pharmacotherapy for the Treatment of Heart Failure

OBJECTIVE: To evaluate acute hemodynamic, short-term, and long-term effects of vasopressin antagonists in patients with heart failure (HF). DATA SOURCES: Searches of the PubMed database (1966-February 2010) were conducted. Search terms included AVP receptor antagonist, CHF, tolvaptan, conivaptan, lixivaptan, HF, and hyponatremia. Manufacturers' prescribing information, manufacturer Web site searches, and searches made on www.clinicaltrials.gov were also included. STUDY SELECTION AND DATA EXTRACTION: All clinical trials identified from the reference search and data sources were reviewed. Articles were included if they were relevant to short-term and long-term outcomes of patients with HF who were treated with vasopressin antagonists. DATA SYNTHESIS: Trials of conivaptan, tolvaptan, and lixivaptan were evaluated. The evidence indicates that all agents increase urine output >10 mL/h, and conivaptan and tolvaptan decrease pulmonary capillary wedge pressure (-2.6 +/- 0.7, -5.4 +/- 0.7, and -4.6 +/- 0.7 mm Hg for placebo, conivaptan 20 mg, and conivaptan 40 mg, respectively; -5.67 +/- 4.58 to -6.38 +/- 4.12 mmHg for tolvaptan, and -4.16 +/- 4.57 mm Hg for placebo) in patients with HF. Both of these changes occur without inducing electrolyte abnormalities or renal dysfunction. Trials with conivaptan in acute HF have not demonstrated a benefit in cardiac index, mean arterial pressure, or vascular resistance. Data from clinical trials indicate that tolvaptan may decrease dyspnea (p < 0.05) and pedal edema (p < 0.001). To date, no large-scale trials of any agent have demonstrated an improvement in left ventricular systolic function, rehospitalization, worsening HF, or death. CONCLUSIONS: Vasopressin antagonists cannot be considered routine pharmacotherapy for HF. Further, conivaptan should not be used for the treatment of acute HF. There is not enough literature to advocate for or against the use of lixivaptan in patients with HF. Tolvaptan may be considered for the treatment of hyponatremia.