Drugs and toxins associated with pulmonary arterial hypertension: from established culprits to novel threats

Pulmonary arterial hypertension (PAH) is a rare form of precapillary pulmonary hypertension. PAH may be idiopathic, heritable, associated with features of pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis, or linked to drug and toxin exposure. Since the first identification of PAH cases associated with drugs and toxins >50 years ago, the number of suspected agents has significantly increased. Following the 6th World Symposium on Pulmonary Hypertension (2018), drugs and toxins have been categorised based on their strength of association with PAH, with nine agents currently classified as definitely associated and 16 as possibly associated. At the 7th World Symposium on Pulmonary Hypertension (2024), carfilzomib and mitomycin C were added as definitely associated with PAH, while bevacizumab and bortezomib were considered as possibly associated with PAH. In cases of suspected PAH following drug or toxin exposure, specific measures are required, including pharmacovigilance reporting, echocardiography, right heart catheterisation to confirm the diagnosis and potential initiation of targeted treatment. Here, we review the latest updates on PAH associated with drugs and toxins.