Bologna, Italy - Sildenafil—the active ingredient in Viagra (Pfizer)—is effective in treating patients with pulmonary arterial hypertension (PAH), according to the results of a study published in the November 17, 2005 issue of the New England Journal of Medicine [1]. The findings from the trial were used to obtain US approval of sildenafil for PAH in the summer of 2005, and European approval has just been granted. This is the first oral treatment for PAH to be approved for patients in the early stages of the disease—the trial was conducted in those with World Health Organization (WHO) class 2 or 3 PAH. Another oral therapy, the dual endothelin receptor antagonist bosentan (Tracleer, Actelion), is available for PAH but was tested in patients with more severe (WHO class 3 or 4) disease.

For PAH, sildenafil is being marketed under a new brand name, Revatio, and is white and round to distinguish it from Viagra's blue diamond shape.

"We now have an additional weapon with which to fight a very difficult battle," lead author Dr Nazzareno Galiè (University of Bologna, Italy) told heartwire.

PAH develops when the arteries supplying the lungs become constricted, leading to right ventricular failure. It can be idiopathic in nature or the result of other conditions, including connective-tissue disease, liver disease with portal hypertension, and HIV infection. It is estimated to affect approximately 100 000 people worldwide. Symptoms include difficulty breathing, dizziness, and fatigue. Left untreated, patients have an average survival time of less than three years from the time of diagnosis.

In the Sildenafil for Use in Pulmonary Arterial Hypertension (SUPER) study, 278 patients with class 2 or 3 PAH were randomized to receive sildenafil (20 mg, 40 mg, or 80 mg) three times a day or placebo.

The primary end point was the change from baseline to week 12 in six-minute-walk distance, the standard measure of efficacy in PAH trials. All three treatment groups showed highly significant improvements (45 to 50 m in walk distance) compared with patients who received placebo (p<0.001 for all three comparisons).

Patients taking sildenafil also showed improvements in mean pulmonary artery pressure, cardiac index, and WHO functional class of PAH.

A long-term nonplacebo-controlled extension trial was also conducted, with 222 patients completing one year of therapy, at which point walk distance and functional class were stable and 94% of patients were still alive.

Galiè says there are now two or three oral treatment options for patients with PAH: "Therapy for this condition used to be quite invasive, but now there are two oral options—bosentan and sildenafil—and we are also looking at combining these two drugs."

He says the decision about which drug to start therapy with is not clear-cut and depends on the individual patient. "I can't say one drug is better than another unless we have a head-to-head comparison, and we don't at this stage." He does note, however, that there are more long-term data on bosentan in PAH than sildenafil at this stage. But in the US, sildenafil is cheaper than bosentan, and this may influence decisions about therapy, he added.

He says his patients have no problem taking a drug designed to treat erectile dysfunction; in fact, he is using Viagra tablets at the moment because Revatio has not yet been widely distributed in Europe.