Advantages and limitations of initial combination therapy in pulmonary arterial hypertension patients in Russia

Pulmonary arterial hypertension (PAH) is severe and often times rapidly progressive disease with fatal outcome. The concept of initial combination of PAH-specific therapies in high risk patients at baseline was first described in the European guidelines on pulmonary hypertension (PH) in 2009, and in low or intermediate risk patients at baseline in 2015. Interestingly, that in Cologne Experts Consensus, and then in the 6th World Symposium on PH medical community started considering initial combination therapy as one of the most important pillars in PAH treatment algorithms in 2018. As of August 2020, as many as 8 formulations of 7 reference PAH-specific drugs are licensed for medical use in the Russian Federation. On top of that, 6 abbreviated drugs (generics) have also become available few years ago. Unfortunately, intravenous and subcutaneous prostacyclin analogs (PCA) and tadalafil are not approved for PH patients treatment in the Russian Federation. In this narrative review paper we attempted to describe studies on initial dual combination therapy with PAH-specific drugs registered in Russia, i.e. ambrisentan and riociguat, macitentan and riociguat, macitentan and sildenafil in low or intermediate risk patients at baseline, as well as iloprost inhaled and sildenafil, iloprost inhaled and bosentan in high risk patients. Some beneficial pharmacological effects due to the synergy between ambrisentan plus riociguat, and inhaled iloprost plus sildenafil appear to be interesting and require further clinical confirmation. Other initial combinations of PAH-specific agents require large-scale clinical trials as well.