Sildenafil May Be Effective for Pulmonary Arterial Hypertension

Oct. 28, 2004 (Seattle) — Sildenafil citrate produced significant improvement in six-minute walk test results of patients with pulmonary arterial hypertension (PAH), according to a randomized, placebo-controlled study presented here during a late-breaking clinical trials session at CHEST 2004, the 70th annual meeting of the American College of Chest Physicians.

Hoissein A. Ghofrani, MD, from the department of internal medicine at the University of Giessen in Germany, said patients receiving 80 mg of sildenafil three times daily increased "six-minute walk results by 50 meters, while patients receiving 40 mg of sildenafil three times daily increased their distance by 46 meters, and patients at the lowest dose [20 mg three times daily] increased by 45 meters." This was significant at P < .001.

The "take-home message is that sildenafil has been shown to be highly effective in a trial that for the first time included a significant proportion of [New York Heart Association (NYHA)] functional class II patients," Dr. Ghofrani told Medscape. Thirty-eight percent of the patients were NYHA class II and 58% were class III.

In addition to improved six-minute walk test results, 35% of patients in the pooled sildenafil groups improved functional class compared with 7% of patients in the placebo group, Dr. Ghofrani said. Moreover, mean pulmonary arterial pressure (mPAP) decreased by an average of 5.1 mm Hg, but this was not statistically significant.

The study, Sildenafil Use in Pulmonary Arterial Hypertension (SUPER-1), enrolled 278 patients randomized to placebo (n = 70) or to one of three doses of sildenafil three times daily: 20 mg (n = 69), 40 mg (n = 68), or 80 mg (n = 71). Seventy-five percent of the patients were women, and the mean age of patients was 49 years.

The mean baseline six-minute walking distance was 344 meters, and the baseline mPAP was 53 mm Hg.

Sildenafil was generally well tolerated, with headache as the most common adverse event (n = 46), but this was not significantly different from headache reported by placebo patients (n = 39).

Although the results for the six-minute walk test reached statistical significance, Thomas Fitzgerald MD, a pulmonologist at Walter Reed Army Medical Center in Washington, D.C., said that it is difficult to judge the clinical impact.

"An improvement of 50 meters on a walking test after 12 weeks of treatment? What does that really mean?" Dr. Fitzgerald asked. "I'm not sure that it is a sign of real improvement." Dr. Fitzgerald cochaired the late-breaking clinical trials session at which the SUPER-1 results were presented.

Alexander Niven, MD, the other session cochair, agreed that it is difficult to assess the data because "with PAH there are no hard clinical end points. I think it will be interesting to see the 12-month results." Dr. Niven is a pulmonologist at Madigan Army Medical Center in Tacoma, Washington.

A long-term trial is ongoing with patients "continuing at the 80-mg dose," Dr. Ghofrani said. The study is about halfway complete, and results will likely be available in six to 12 months, he said.

Dr. Niven added, however, that another oral treatment would be welcome because the only approved oral drug for PAH, bosentan (Trocleer; Actelion Pharmaceuticals) is expensive; Dr. Ghofrani estimated bosentan's annual cost at $40,000.

The SUPER-1 study was funded by Pfizer, the maker of sildenafil.

CHEST 2004: Late-breaking clinical trial session. Presented Oct. 27, 2004.

Reviewed by Gary D. Vogin, MD