Nitrogen oxide biochemical pathway in pulmonary arterial hypertension therapy and REPLACE trial results

Endogen nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) deficiency in pulmonary vessels walls plays essential role in pulmonary arterial hypertension (PAH) pathogenesis. Soluble guanylate cyclase stimulator riociguat and phosphodiesterase-5 (PDE5) inhibitor sildenafil increase cGMP content and have proven clinical efficacy in PAH treatment. The potentially beneficial mechanisms of riociguat mechanism of action include endogen NO independence in cGMP synthesis and its independence from other phosphodiesterase isoferments (other than PDE5). Clinical options, safety and effectiveness of iPDE5 – riociguat transition in patients with PAH were for the first time shown in non-controlled study RESPITE and the assessment is continued in randomized placebo-controlled trial REPLACE