Pulmonary hypertension · Phosphodiesterase-5 inhibitors
Sildenafil citrate therapy for pulmonary arterial hypertension
| Design | Randomised, double-blind, placebo-controlled trial with three dose arms |
|---|---|
| Treatment | Sildenafil 20 mg, 40 mg or 80 mg three times daily |
| Control | Placebo |
| Population | 278 patients with symptomatic pulmonary arterial hypertension |
| Follow-up | 12 weeks |
| Primary endpoint | Change in six-minute walk distance at 12 weeks |
| Result | Placebo-corrected treatment effects on six-minute walk distance were 45 m (+13.0%), 46 m (+13.3%) and 50 m (+14.7%) for 20, 40 and 80 mg respectively (p<0.001 for all). All doses reduced mean pulmonary artery pressure and improved WHO functional class. Side effects included flushing, dyspepsia and diarrhoea. Clinical worsening did not differ significantly. |
| Secondary endpoints | Mean pulmonary artery pressure, WHO functional class, clinical worsening |
Sildenafil improves exercise capacity, WHO functional class, and hemodynamics in patients with symptomatic pulmonary arterial hypertension.
The trial authors, in the published abstract
Made an oral, cheap, widely available drug a first-line option and remains the backbone of combination regimens such as AMBITION. The flat dose-response is the practical finding: 20 mg three times daily is the licensed dose because higher doses added nothing. Twelve weeks and a walk-distance endpoint, which the later event-driven trials superseded.
Galiè N, Ghofrani HA, Torbicki A, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 2005 Nov 17;353(20):2148-57.