Drug-Induced Pulmonary Hypertension: The First 50 Years

Drug-induced pulmonary arterial hypertension (D-PAH) is a form of World Health Organization Group 1 pulmonary hypertension (PH) characterized by severe small vessel loss and obstructive vasculopathy, which leads to progressive right heart failure and death. To date, 16 different compounds have been associated with D-PAH, including anorexinogens, recreational stimulants, and more recently, several Food and Drug Administration-approved medications. While the clinical manifestations, pathology, and hemodynamic profile of D-PAH are indistinguishable from other forms of PAH, its clinical course can be unpredictable and largely dependent on removal of the offending agent. Since only a subset of individuals develop D-PAH, it is likely that genetic susceptibility plays a role in pathogenesis, but characterization of the genetic factors responsible for disease susceptibility remains incomplete. Besides aggressive treatment with PH-specific therapies, the major challenge in the management of D-PAH remains the early identification of compounds capable of injuring the pulmonary circulation in susceptible individuals. Institution of pharmacovigilance, precision medicine strategies, and global warning systems will help facilitate identification of high-risk drugs and institute regulation strategies to prevent further outbreaks of D-PAH.