An Update on Medical Therapy for Pulmonary Arterial Hypertension

Abstract

Over the past 20 years, great progress has been made in the treatment of pulmonary arterial hypertension (PAH). Available therapies target one of three principal pathways: the endothelin (ET), nitric oxide (NO) or the prostacyclin (PGI2) pathway. Evidence shows that current drugs, used either as monotherapy or in different combinations, can improve exercise capacity, clinical symptoms, hemodynamics and even survival in PAH. Unfortunately, the disease remains incurable and the prognosis of the disease is still poor. However, existing and novel potent antiproliferative therapies are being explored, and new agents targeting different and/or additional pathways are likely to become available to clinicians in the near future. Promising candidates include tyrosine kinase antagonists (e.g. imatinib); soluble guanylate cyclase stimulators (riociguat); an oral analog of prostacyclin (selexipag); and a tissue targeting endothelin receptor antagonist (macitentan). Phase II or III trials have either been completed or are underway to evaluate the safety and efficacy of these various therapies.

Targeted Delivery of Pulmonary Arterial Endothelial Cells Overexpressing Interleukin-8 Receptors Attenuates Monocrotaline-Induced Pulmonary Vascular Remodeling

“…Cell- and gene-based therapies for pulmonary arterial diseases have proliferated over the past years, but with limited success (10,11,12). Cell-based therapies have been shown to alleviate pulmonary hypertension and RV dysfunction, but the majority of the studies are currently at the preclinical level in animal models (11,13,14,15,16).…”

Nuevos agentes para el tratamiento de la hipertensión pulmonar

“…La hipertensión pulmonar asociada a anemia hemolítica crónica se transfirió del grupo 1 al 5 (mecanismos multifactoriales/poco claros); además, se agregaron otros términos relacionados con hipertensión pulmonar pediátrica (tabla 1) 15 . Tratamiento La terapia con medicamentos aprobados para hipertensión arterial pulmonar debe iniciarse en pacientes sin vasorreactividad o sin respuesta adecuada a los calcioantagonistas 16 . Los antagonistas del receptor de endotelina, los inhibidores de la fosfodiesterasa tipo 5 (PDE5i) y los análogos de la prostaciclina y del óxido nítrico son eficaces y seguros para mejorar el perfil hemodinámico pulmonar, el cuadro clínico, y en algunos casos, la supervivencia en hipertensión arterial pulmonar idiopática, así como en otras formas de hipertensión arterial pulmonar 2 .…”

Acetyl-lysine erasers and readers in the control of pulmonary hypertension and right ventricular hypertrophy

“…The 5 year mortality rate for individuals with PH is ~50%, underscoring an urgent need for novel therapeutics (McLaughlin et al 2009). Standards-of-care (SOC) for PH patients includes the use of vasoactive drugs, including endothelin receptor antagonists (ERAs), phosphodiesterase-5 (PDE-5) inhibitors, and prostacyclins (Wu et al 2013). Many have postulated that more effective therapeutic strategies will be based on the combined use of vasodilators and agents that target distinct pathogenic mechanisms in PH, such as pulmonary vascular inflammation and fibrosis, as well as uncontrolled proliferation of smooth muscle cells, endothelial cells and fibroblasts in the lung vasculature (Humbert et al 2004).…”