SAN FRANCISCO — In a pilot study, researchers found that midodrine and a combination of midodrine and tolvaptan plus standard medical therapy better controls refractory or recurrent ascites and improves systemic hemodynamics among patients with cirrhosis, according to a presidential poster of distinction presented at The Liver Meeting 2015.
“Splanchnic arterial vasodilatation and subsequent activation of antinatriuretic and vasoconstrictive mechanisms resulting in sodium and water retention play an important role in cirrhotic ascites,” Virendra Singh, MD, DM, FASGE, of the Postgraduate Institute of Medical Education and Research, Chandigarh, India, told Healio.com/Hepatology. “Between 5 and 10% of patients with cirrhosis have this….The aim of this study was to evaluate the effects of midodrine, tolvaptan and their combination on systemic hemodynamics, renal function and control of ascites in patients with cirrhosis and refractory or recurrent ascites.”
Singh and colleagues randomly assigned 50 patients with cirrhosis and refractory or recurrent ascites to long-term treatment with midodrine three times per day (n = 13) or tolvaptan twice per day (n = 12), a combination of midodrine and tolvaptan (n = 13) plus standard medical therapy (SMT) or SMT alone (n = 12).
Analyses showed that midodrine alone and midodrine in combination with tolvaptan plus SMT was more superior compared to tolvaptan or SMT alone for controlling ascites (P < .05). At 1 month, combination therapy was more effective compared with midodrine alone (46% vs. 0%; P = .014), with an upward trend towards improved control of ascites by 3 months (69% vs. 39%; P = .12).
“This drug [tolvaptan], if it is given for a few months, days or weeks, it doesn’t cause the hepatic dysfunction,” Singh said. “Together and without midodrine. I’ve used it for months here and [hardly any] hepatic dysfunction occurred.”
Increases in urinary volume and urinary sodium excretion and a decrease in plasma renin activity were observed in all groups except the SMT alone group. The mean arterial pressure and systemic vascular resistance both increased significantly in the midodrine alone group (P < .05).
“The mortality and frequency of various complications were similar in all the groups, except SMT in which renal failure was observed in a significantly higher number of patients,” Singh said.
A previous study
performed by Singh and colleagues in 60 patients with cirrhosis and ascites treated with midodrine, clonidine or standard therapy alone yielded similar results to this pilot study, in which standard medical care was also inferior to the combination regimens. In another study by Singh and colleagues in 40 patients, midodrine plus standard medical therapy was significantly superior to standard medical therapy alone in the control of refractory/recurrent ascites (P =
.013) and had better survival at 3 months.
Singh concluded: “The combination therapy is superior to midodrine or tolvaptan alone in the control of ascites.” – by Melinda Stevens
Singh V, et al. Abstract 259. Presented at: The Liver Meeting; Nov. 13-17, 2015; San Francisco.
Disclosures: The researchers report no relevant financial disclosures.