Efectos de satavaptan sobre la hiponatremia, la gestión de la ascitis y la morbilidad en la cirrosis hepática en un estudio controlado con placebo a largo plazo

INTRODUCTION:

Cirrhotic patients with ascites and hyponatremia have advanced liver disease with many complications. Their ascites is difficult to manage with natriuretic agents because of the presence of hyponatremia. Vasopressin V2-receptor antagonists have been shown in shortterm studies to correct hyponatremia in such patients.

AIM:

To investigate the long-term effects of treatment with satavaptan, a selective vasopressin V2-receptor antagonist, on hyponatremia, the management of ascites and other complications in patients with liver cirrhosis.

PATIENTS/METHODS:

Patients with liver cirrhosis, ascites and a history of hyponatremia (serum sodium ?130 mmol/l) were randomized into a multicentre, single-blind study to receive in a 2:1 ratio either a flexible dose-regimen of satavaptan (5-50 mg once daily) or placebo. Diuretics and paracentesis were used as required. Planned duration of treatment was up to 52 weeks. Parameters measured included serum sodium, number of paracenteses, hospitalisation and incidence of complications of cirrhosis. Number of normonatremic days was estimated from serum sodium values measured at regular intervals. Results:139 patients were randomised, 92 to satavaptan and 47 to placebo. The estimated number of normonatremic days (serum sodium ?135 mmol/l) over 1 year was 208 days for patients treated with satavaptan vs. 93 days for placebo (p<0.001).The estimated mean number of paracenteses/patient over 1 year was 4.3 for satavaptan vs. 6.1 for placebo(relative risk 0.75, n.s.). Median time to first hospitalisation for any cause was 32 weeks for satavaptan vs. 10 weeks for placebo(relative risk 0.62, p=0.03). Mean total duration of hospitalisation/year/patient was 15 days for satavaptan vs. 29 days for placebo (p=0.08). Laboratory assessments showed Kaplan-Meier 52-week estimated probability of serum potassium ?5.5mmol/l was 45.3% for satavaptan and 31.5% for placebo, and for serum creatinine increase (?50% from baseline and >1.5 mg/dl) was 32.5% for satavatan and 27.4% for placebo. The estimated probabilities of other major complications of cirrhosis are shown in the table.

CONCLUSION:

Satavaptan showed a longterm improvement of hyponatremia with trends towards improvements in ascites and a reduction in hepatic encephalopathy and variceal bleeding, but a higher probability of elevated serum potassium and creatinine.