SEATTLE — A 12-week course of sildenafil citrate in adults with pulmonary arterial hypertension significantly improved 6-minute walking distance and mean pulmonary artery pressure, and had favorable effects on New York Heart Association functional class, H. Ardeschir Ghofrani, M.D., reported at the annual meeting of the American College of Chest Physicians.
“Sildenafil was not only highly effective in achieving improvement in 6-minute walking distance, but it also showed a very favorable safety profile,” he said in an interview.
It appears to be a very “good drug” for treating pulmonary arterial hypertension, but as promising as these data appear, physicians should not use the drug off label, as “this really should be addressed in controlled trials,” Dr. Ghofrani said.
In a multicenter, international trial, Dr. Ghofrani and his associates enrolled 278 patients with pulmonary hypertension and randomized them to placebo or sildenafil three times daily for 12 weeks.
Most of the patients (75%) were female, and the average age was 49. Overall, 63% had primary pulmonary hypertension and 30% had connective tissue disease. Most of the patients (58%) had New York Heart Association functional class III disease and 39% had class II disease.
Of the 278 patients, 70 took placebo t.i.d., 69 took 20 mg sildenafil t.i.d., 68 took 40 mg sildenafil t.i.d., and 71 took 80 mg sildenafil t.i.d.
The primary end point was change from baseline at week 12 in exercise capacity as measured by 6-minute walking distance.
Compared with patients who took a placebo, those assigned to take sildenafil had significant improvements in 6-minute walking distance.
The mean placebo-corrected treatment effect was 45 meters in the 20-mg group, 46 meters in the 40-mg group, and 50 meters in the 80-mg group.
“The improvements were slightly more pronounced in patients who had lower 6-minute walking distances at baseline, showing improvements up to 80 meters in the 80-mg group, whereas the patients who were doing better at baseline still had significant improvements,” said Dr. Ghofrani of Giessen, Germany, who is a paid consultant to Pfizer, which manufactures sildenafil.
All sildenafil doses reduced mean pulmonary artery pressure by week 12. The mean reductions were 2.7 mm Hg in the 20-mg group, 3.0 mm Hg in the 40-mg group, and 5.1 mm Hg in the 80-mg group.
The proportion of patients who improved by at least one New York Heart Association functional class was 35% in the sildenafil group and 7% in the placebo group.
The investigators also observed a trend toward decreased hospitalizations and improvements in shortness of breath during exercise among patients on sildenafil.
The most common adverse events experienced by patients on sildenafil, compared with those on placebo, were headache, flushing, dyspepsia, and back pain.
Pfizer Global Research and Development funded the study.