Case Report

Long-term Results After Addition of Sildenafil in Idiopathic PAH Patients on Bosentan

Authors: Omar A. Minai, MD, FCCP, Alejandro C. Arroliga, MD, FCCP


Idiopathic pulmonary arterial hypertension is a disease involving small muscular pulmonary arteries and arterioles. Treatment with prostacyclin analogs and endothelin receptor antagonists is the cornerstone of therapy in these patients. Recent evidence suggests that phosphodiesterase-5 inhibitors such as sildenafil may improve functional capacity and hemodynamics in patients with pulmonary arterial hypertension. Despite these advances, pulmonary arterial hypertension remains a deadly and progressive disease and it has been suggested that combination therapy aimed at multiple targets may produce a greater improvement while minimizing adverse effects. We report three patients who declined after initial improvement on bosentan and subsequently showed an improvement in their functional capacity and brain natriuretic peptide (BNP) with the addition of sildenafil. This benefit has been sustained over a mean follow-up period of 19 (range 12–24) months.

Key Points

* Patients with pulmonary arterial hypertension declining on monotherapy may obtain benefit from the addition of a second agent.

* Combination therapy can produce sustained clinical improvement in patients with pulmonary hypertension.

This content is limited to qualifying members.

Existing members, please login first.

If you have an existing account please login now to access this article or view your purchase options.

Purchase only this article ($15)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.


1. McGoon M, Gutterman D, Steen V, et al. Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practical guidelines. Chest 2004;126:14S–34S.
2. Channick RN, Sitbon O, Barst RJ, et al. Endothelin receptor antagonists in pulmonary arterial hypertension. J Am Coll Cardiol 2004;43:62S–67S.
3. McLaughlin VV, Shillington A, Rich S. Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Circulation 2002;106:1477–1482.
4. Galie N, Ghofrani HA, Torbicki A, et al. Sildenafil citrate therapy for pulmonary arterial hypertension.N Engl J Med 2005;353:2148–2157.
5. Rubin LJ, Galie N. Pulmonary arterial hypertension: a look to the future. J Am Coll Cardiol 2004;43(12 Suppl S):89S–90S.
6. Galie N, Seeger W, Naeije R, et al. Comparative analysis of clinical trials and evidence-based treatment algorithm in pulmonary arterial hypertension. J Am Coll Cardiol 2004;43:81S–88S.
7. Stewart DJ, Levy RD, Cernacek P, Langleben D. Increased plasma endothelin-1 in pulmonary hypertension: marker or mediator of disease. Ann Intern Med 1999;114:464–469.
8. Giaid A, Yanagisawa M, Langleben D, et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med 1993;328:1732–1739.
9. Rubin LJ, Badesch DB, Barst RJ, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 2002;346:896–903.
10. Sitbon O, Badesch DB, Channick RN, et al. Effects of the dual endothelin antagonist bosentan in patients with pulmonary arterial hypertension: a 1-year follow-up study. Chest 2003;124:247–254.
11. McLaughlin VV, Sitbon O, Badesch DB, et al. Survival with first-line bosentan in patients with primary pulmonary hypertension. Eur Respir J 2005;25:244–249.
12. Ghofrani HA, Wiedemann R, Rose F, et al. Combination therapy with oral sildenafil and inhaled iloprost for severe pulmonary hypertension. Ann Intern Med 2002;136:515–522.
13. Michelakis E, Tymchak W, Lien D, et al. Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: comparison with inhaled nitric oxide.Circulation 2002;105:2398–2403.
14. Ghofrani HA, Wiedemann R, Rose F, et al. Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomised controlled trial. Lancet 2002;360:895–900.
15. Ghofrani HA, Rose F, Schermuly RT, et al. Oral sildenafil as long-term adjunct therapy to inhaled iloprost in severe pulmonary arterial hypertension. J Am Coll Cardiol 2003;42:158–164.
16. Hoeper MM, Faulenbach C, Golpon H, et al. Combination therapy with bosentan and sildenafil in idiopathic pulmonary arterial hypertension. Eur Respir J 2004;24:1007–1010.
17. Mughal MM, Mandell B, James K, et al. Implementing a shared care approach to improve the management of patients with pulmonary arterial hypertension. Cleve Clin J Med 2003;70(Suppl 1):S28–S33.