Optimization of specific therapy for pulmonary arterial hypertension: the possibilities of using endothelin receptor antagonists

Modern concepts of pulmonary arterial hypertension (PAH) pathogenesis focus on the key role of endothelial dysfunction of pulmonary vessels. To control the activation of endothelin-1 system, endothelin receptor antagonists (ERA) are current ly used. Until recently, this class of drugs in our country and abroad was represented by two drugs: the sulfonamide derivative - a nonselective ERA bosentan and a non-sulfonamide derivative - ambrisentan, which blocks only ETA-receptors. Not the selectivity of ERAs, but their pharmacokinetic characteristics determine the differences in the profile of efficacy and safety. In 2015, in our country there appeared a new dual antagonist macitentan, which was created to optimize the tissue effects by increasing lipophilicity. In randomized SERAPHIN study, the use of macitental 10 mg compared with placebo contributed to a reduction of the risk of morbidity and mortality in patients with PAH by 45%, and the effect of therapy was not dependent on whether the patients received concomitant specific therapy with inhibitors of phosphodiesterase type 5, oral or inhaled prostanoids. In the paper there summarized indications for prescribing ERA, the data of the evidence base, as well as the concept of switching to optimize the ERA treatment. It is important to emphasize that in case of a satisfactory clinical response with ERA therapy, correction of therapy seems discrete. In the European guidelines 2015, this issue is not considered as having no extensive evidence base. On the other hand, it cannot be ruled out that the use of generic bosentan may lead to a decrease in the treatment effecacy and to provoke the clinical deterioration. At present clinical data intensively accumulate in favor of the strategy of switching from bosentan or ambrisentan to macitentan in PAH patients. It is necessary to assess the potential benefits associated with ERA switching to macitentan, in comparison with the possibilities of combination therapy.