Clinical Question: Can sildenafil increase quality of life in patients with primary pulmonary hypertension?

Setting: Outpatient (specialty)

Study Design: Crossover trial (randomized)

Synopsis: Investigators evaluted the effect of sildenafil in 22 patients between 16 and 55 years of age with primary pulmonary hypertension, a New York Heart Association functional classification of II to III, and mean pulmonary artery pressure of at least 30 mm Hg. Patients were assigned randomly to receive sildenafil in a dosage of 25 to 100 mg three times daily (depending on body weight) or placebo for six weeks, followed by evaluation and then cross over to the other treatment for an additional six weeks. In this way, each patient served as his or her own control subject, which allowed conclusions to be drawn using a smaller number of patients. Use of nitrates or other vasodilators was not allowed during the study.

In patients taking sildenafil, quality of life, which was measured by a chronic heart failure questionnaire, improved on the dyspnea score (22 versus 17.6 out of a possible 35; P < .05) and fatigue score (22.2 versus 20.7 out of a possible 28; P < .05), but scores on the emotional function scale did not differ. Treadmill exercise time was unaffected by placebo when it was given first but increased by 3.8 minutes (from a baseline measure of 7.7 minutes) with sildenafil treatment. In patients who received sildenafil first, exercise time was increased by 4.1 minutes, but placebo treatment resulted in a statistically significant 1.3 minutes. Cardiac index improved, but pulmonary artery systolic pressure was not affected significantly. This dosing regimen, at a cost of approximately $25 per day, is expensive (about $9,000 per year).

Bottom Line: Sildenafil in high dosages produces significant improvements in fatigue and dyspnea scores and increases treadmill walking time by approximately four minutes in patients with primary pulmonary hypertension. It is an option—an expensive one—for the treatment of a disorder that has few good treatments. (Level of Evidence: 1b)