Long-term experience with oral or inhaled vasodilator combination therapy in patients with pulmonary hypertension

Abstract

BACKGROUND: Disease progression in pulmonary hypertension (PH) is common despite standard vasodilator monotherapy with iloprost, bosentan or sildenafil. OBJECTIVE: To investigate if the combination of these non-invasively applicable treatments is an effective option to address the multiple pathophysiological mechanisms present in PH. METHODS: We analysed the clinical course of 23 patients with PH, diagnosed as idiopathic (n = 15), chronic thromboembolic (n = 4), and associated with collagen vascular disease (n = 4), receiving combination vasodilator therapy at our institution. RESULTS: Vasodilator therapy before combination therapy consisted of inhaled iloprost (I; n = 12), or oral bosentan (B; n = 6) at a mean duration of 19 +/- 3 months. The combination therapy added was B (n = 8), sildenafil (S; n = 6) or I (n = 4) and in five patients, combination therapy was given from the beginning (3x BS, 1x IS, 1x IBS). Under combination therapy, the 6-minute walk distance (6MWD) increased significantly by 46.7 +/- 24.8 m (p = 0.02) after three months, and after six months it was still 38.3 +/- 28.3 m (p = 0.17) longer than before combination therapy. Respective changes in the Borg Scale and the NYHA functional class were -1.05 +/- 0.49 (p = 0.014) and -0.42 +/- 0.19 (p = 0.02) after three months and -0.21 +/- 0.65 (p = 0.61) and -0.38 +/- 0.29 (p = 0.26) after six months. Only minor side effects were reported. CONCLUSION: Combination vasodilator therapy in severe PH is safe and well tolerated. It significantly improves exercise capacity and stabilises the functional class in patients with severe PH deteriorating under single-agent therapy