These costly drugs did not reduce mortality in a meta-analysis of randomized, controlled trials.

In patients with cirrhosis, hemodynamic changes lead to increased secretion of arginine vasopressin, which results in water retention and dilutional hyponatremia. Vaptans (nonpeptide vasopressin receptor antagonists) promote increased free water clearance with hypotonic dieresis. Although vaptans are approved for use in hyponatremic patients, their efficacy and safety in patients with cirrhosis is debated.

Now, investigators have conducted a systematic review and meta-analysis of 12 industry-funded, randomized, controlled trials that evaluated the safety and efficacy of vaptans (tolvaptan, satavaptan, and lixivaptan) in patients with cirrhosis and hyponatremia or ascites. Of 2266 total participants, 1483 received vaptans, and 783 controls received no intervention, placebo treatment, or a different diuretic agent (furosemide or spironolactone). The primary outcome was mortality; secondary outcomes included complications of cirrhosis, renal failure, serum sodium levels, mobilization of ascites, and adverse events.

Mortality was similar in the vaptan and control groups, as were rates of complications of cirrhosis and renal failure. Compared with controls, use of vaptans increased serum sodium levels (weighted mean difference, 2.02 mmol/L), reduced body weight (weighted mean difference, –1.82 kg), increased the time to the first large-volume paracentesis, and increased the rate of nonserious adverse events such as thirst and excessive urine volume. Subgroup and sensitivity analysis did not alter these findings.

Comment: This well executed meta-analysis demonstrated no survival benefit from the use of vaptans in patients with cirrhosis and ascites or hyponatremia. Although no serious adverse events occurred with the use of vaptans, nonserious adverse events were common. Because this class of drugs is expensive and its benefits are questionable, it cannot be recommended for routine clinical use in patients with cirrhosis.

Source: Journal Watch Gastroenterology