Update on the clinical utility of sildenafil in the treatment of pulmonary arterial hypertension

Abstract

Sildenafil is an orally administered phosphodiesterase type 5 inhibitor that is approved for the treatment of pulmonary arterial hypertension (PAH). The hemodynamic effects of sildenafil are mitigated primarily via potentiating the effects of endogenous nitric oxide, leading to smooth muscle cell relaxation and reductions in pulmonary arterial pressures and pulmonary vascular resistance. When added to standard background therapy in patients with idiopathic or associated PAH from congenital heart disease, anorexigen use, or connective tissue disease, sildenafil treatment results in improved exercise capacity as measured by 6 minute walk distance, improved hemodynamics, and favorable changes in quality of life. Sildenafil use is contraindicated with concomitant nitrate administration, and caution should be exercised when used in combination with antihypertensive agents due to risks of precipitating hypotension. Side effects are generally mild, and include flushing, headaches, and epistaxis. The combination of sildenafil with intravenous epoprostenol is safe and well tolerated, and further improves exercise capacity. Sildenafil is approved only for treatment of PAH, and although emerging data suggest a potential role in treating other types of pulmonary hypertension, larger trials are required to confirm these findings.

Keywords: phosphodiesterase type 5 inhibitor; pulmonary arterial hypertension; sildenafil.

Figure 1

Cellular mechanisms of sildenafil actions. Reproduced with permission from Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004;351:1425–1436. Copyright © 2004 Massachusetts Medical Society. All rights reserved. Abbreviation: cGMP, cyclic guanosine monophosphate.

Figure 2

Endothelial cell. Abbreviations: cGMP, cyclic guanosine monophosphate; PDE, phosphodiesterase; SMC, smooth muscle cell.