This could explain why combined therapy for PAH has proven to be more effective than single therapy, with the European Society of Cardiology (ESC) and European Resuscitation Council (ERC) guidelines 2015, recommending the use of dual therapy in PAH by using a combination of the Phosphodiesterase type 5 inhibitor (PDE5) and Endothelin-1 (ET-1) drugs as the first-line therapy [130]. The gene discussed is EDN1; the disease is pulmonary arterial hypertension.