Sildenafil May Improve Quality of Life in IPF Patients

BY CRAIG GUILLOT
Elsevier Global Medical News

NEW ORLEANS — Sildenafil might improve quality-of-life indicators in patients with idiopathic pulmonary fibrosis, according to the first multicenter, randomized trial to enroll patients at an advanced stage of the disease. However, the Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis (STEP-IPF) failed to show an effect ofthe drug on lung function, the study’s primary end point.

The improvement in quality-of-life measures, a secondary end point in the study, is encouraging, said Dr. David A. Zisman, FCCP, of the interstitial lung disease program at the University of California, Los Angeles.

For the double-blind, placebo-controlled trial, the researchers recruited 180 participants from 14 IPF Clinical Research Network (IPFnet) centers across the country. Patients were randomized to receive oral sildenafil (20 mg, three times daily) or placebo for 12 weeks.

By the end of that period, nine subjects in the sildenafil group and six in the placebo group had increased their distance in the 6-minute walk trial by at least 20%— a standardized indicator of lung function. The difference was not significant.

But participants taking sildenafil had slightly better arterial oxygenation and reported less shortness of breath, Dr. Zisman said at an international conference of the American Thoracic Society. The study was also published online (N. Engl. J. Med. 2010 May 18 [doi:10.1056/ NEJMoa1002110]).

The team did three tests of quality of life, including the St. George’s Respiratory Questionnaire, in which a higher total indicates worse function. At 12 weeks, the sildenafil group had a total score of –1.64, and the placebo group scored 2.45.

On the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), the sildenafil group better preserved its general health score, a subcategory of the test. The third quality-of-life test, the EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D), showed no significant difference.

“I think this mainly opens the door and promises another avenue to treat or slow progression of the disease,” Dr. Zisman said. He added that sildenafil might be of value to patients with advanced IPF and that the data could prompt further trials. The results also suggest that phosphodiesterase type 5 inhibition might have a role in slowing disease progression, he said.

No major difference was seen in serious adverse effects with the drug and placebo. During the trial, two people died in the sildenafil group, and four died in the placebo group.

Sildenafil stabilizes cyclic guanosine monophosphate (cGMP) and leads to vasodilatation in well-ventilated areas of the lung. It is manufactured by Pfizer under the brand names Revatio and Viagra.

Dr. Zisman disclosed that he is on the advisory board of Gilead Sciences. The STEP-IPF study was funded by the National Institutes of Health.

Dr. Philip Marcus, MPH, FCCP, comments:
Sildenafil has been used for the treatment of pulmonary hypertension, and in the population of patients with IPF, many do develop pulmonary hypertension. Accordingly, whether sildenafil treats the disease or slows progression of IPF may be overshadowed by the ability of this PDE5 inhibitor to reduce pulmonary vascular resistance and improve quality of life.