Efficacy and Safety of Upfront Combination of ΒΟsentan and ΤΑdalafil in Pulmonary Arterial Hypertension

The development of disease-targeted drugs for the treatment of pulmonary arterial hypertension (PAH) has significantly improved within the last years. Combining drug products with different mechanisms of action such as Endothelin-Receptor-Antagonists (ERAs) and Phosphodiesterase-Type-5-inhibitors (PDE-5-Inhibitors) has become increasingly important for the treatment of PAH. Recently, the results of the AMBITION study reported that an upfront combination treatment of ambrisentan and tadalafil immediately after diagnosis leads to a delayed disease progression. On the other hand, the sequential combination of bosentan and sildenafil did not show a similar positive clinical effect and this was attributed to a negative clinically relevant pharmacodynamic drug-drug interaction. Although, recent guidelines have extrapolated that initial upfront combination treatment follows a class effect in terms of efficacy and safety, there is an imperative need to support this notion with other combinations of ERAs and PDE-5-Inhibitors.