The pharmacological treatment of pulmonary arterial hypertension.
Pulmonary arterial hypertension (PAH) is a life-threatening and progressive disease of various origins characterized by pulmonary vascular remodeling that leads to increased pulmonary vascular resistance and pulmonary arterial pressure, most often resulting in right-sided heart failure. The most common symptom at presentation is breathlessness, with impaired exercise capacity as a hallmark of the disease. Advances in understanding the pathobiology over the last 2 decades have led to therapies (endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, and prostacyclins or analogs) initially directed at reversing the pulmonary vasoconstriction and more recently directed toward reversing endothelial cell dysfunction and smooth muscle cell proliferation. Despite these advances, disease progression is common even with use of combination regimens targeting multiple mechanistic pathways. Overall 5-year survival for PAH has increased significantly from approximately 30% in the 1980s to approximately 60% at present, yet remains abysmal. This review summarizes the mechanisms of action, clinical data, and regulatory histories of approved PAH therapies and describes the latest agents in late-stage clinical development.
lfrumkin@stanford.edu
Lyn R
LR
Frumkin
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D055808:Drug Discovery; D065627:Familial Primary Pulmonary Hypertension; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects
D000959:Antihypertensive Agents