Clinical

Sildenafil shows promise for portopulmonary hypertension

Last Updated: 2006-08-30 18:20:45 -0400 (Reuters Health)

By Megan Rauscher

NEW YORK (Reuters Health) - A small German study suggests that oral sildenafil may be effective for portopulmonary hypertension, a subtype of pulmonary arterial hypertension.

Oral sildenafil, with or without inhaled prostanoid therapy, led to significant clinical, functional, and hemodynamic improvement or stabilization, investigators report in the European Respiratory Journal for September.

"Hypertension is a serious complication in liver cirrhosis that may affect up to 10% of patients with liver cirrhosis at any stage," lead author Dr. Frank Reichenberger from University Hospital Giessen noted in comments to Reuters Health. "The disease leads to progressive limitation in exercise capacity and, if untreated, it is currently regarded as contraindication for liver transplantation."

Presently, there is no established treatment for this condition. However, small case series have reported the successful compassionate use of prostanoids (inhaled iloprost or IV epoprostenol), as well as bosentan, an oral medication for pulmonary arterial hypertension.

"These therapies, however, are hampered by significant effort in patient compliance or are potentially hazardous in the case of bosentan, which exhibits liver toxicity in 10% of patients," Dr. Reichenberger noted.

Therefore, he and colleagues treated 10 women and 4 men with moderate-to-severe portopulmonary hypertension caused by various types of liver disease with oral sildenafil, which was recently licensed for the treatment of pulmonary arterial hypertension.

Sildenafil was given in escalating doses, reaching 50 mg three times daily within 3 weeks.

"We included patients with portopulmonary hypertension who were newly commenced on this therapy, and patients who were already on therapy with inhaled prostanoids but did deteriorate on this treatment," Dr. Reichenberger noted.

"In both patient groups, we found a significant improvement in clinical performance (NYHA-classification), functional capacity (6-minute walking distance), and hemodynamic parameters (using right heart catheter), after 3 months and a stable condition after 1 year of treatment," the investigator reported.

There was a similar response to sildenafil treatment in patients on monotherapy and those on combination therapy.

Oral sildenafil was safe and well tolerated in this patient population. "Notably," the authors say, "there were no reported episodes of gastrointestinal hemorrhage, as has been reported previously."

Two patients died within two months of starting sildenafil -- one from liver failure and the other from cardiac failure.

In an editorial, Drs. M. J. Krowka and K. L. Swanson from the Mayo Clinic, Rochester, Minnesota, note that, in this small, uncontrolled trial, oral sildenafil "appeared to provide therapeutic benefit...when evaluated at 3 months, but the hemodynamic benefit was not sustained at 12 months in 7 patients."

"Curiously, the 6-minute walk distance did continue to improve at both 3 and 12 months," they further note. "This illustrates the importance of longer-term follow-up in pulmonary hypertension trials than the usual 12- to 16-week endpoints."

Drs. Krowka and Swanson conclude that "optimal treatment for portopulmonary hypertension remains an unanswered, but important question."

Eur Respir J 2006;28:466-467,563-567.