Emerging therapies for the treatment of pulmonary arterial hypertension

Besides all progress in the therapy of pulmonary arterial hypertension over the past years, there is still no cure for this devastating disease. By introducing effective and nonparenteral medications (e.g., oral endothelin receptor antagonists [ERAs],inhaled prostanoids), quality of life,exercise tolerance and prognosis of patients have substantially improved. However, applicability of these therapies can be hampered by serious side effects and/or the necessity for elaborate application techniques. Whether selective ERAs - due to their specificity for the A-type receptor - have potential benefits over the nonselective ERA bosentan remains to be answered by the analysis of pivotal trials recently carried out with ambrisentan and sitaxsentan. Inhaled treprostinil can potentially have benefits over the already approved inhaled iloprost, related to its higher pulmonary selectivity as well as to the longer biological half-life. However, this has yet to be proven in long-term randomized controlled trials, In comparison to the previously mentioned substances, the selective phosphodiesterase-5 (PDE5) inhibitor sildenafil approached approval closest as new therapy for pulmonary arterial hypertension. Oral sildenafil has proven its efficacy as a selective pulmonaryvasodilator in various forms of pulmonary hypertension. The results of the pivotal phase III trial have confirmed the strong efficacy and excellent tolerability of this substance. Combination therapies, despite all progress seen for single agents, can be regarded as the most promising therapeutic approach for the future. However, controlled randomized trials that are currently under consideration have to confirm this notion.