Evolving nonvasodilator treatment options for pulmonary arterial hypertension

Purpose of review With the establishment of vasodilator therapy as a mainstay of treatment for pulmonary arterial hypertension (PAH), new therapeutic approaches are needed to prevent the development of the vasculopathy associated with this disease. Many studies are currently underway to investigate nonvasodilator treatment options. Recent findings Modulation of bone morphogenic protein receptor type 2 (BMPR2) signaling with sotatercept showed promising results in phase 2 studies. Rituximab, an anti-CD20 monoclonal antibody, showed some signal for beneficial effect in patients with scleroderma-associated PAH. Studies evaluating agents including tocilizumab, selonsertib, bardoxolone, 10-nitro-9(E)-enoic acid (CXA-10) and intravenous iron have not shown acceptable efficacy in treating PAH. Pharmacologic approaches for the treatment of PAH include altering of transforming growth factor beta/BMPR2 signaling, proliferation via growth factors, immune response, oxidative stress, estrogen signaling, metabolism, and neurohormonal modulation. Other treatment modalities including pulmonary artery nerve denervation, stem cell therapy, and inter-atrial shunt formation are also being explored.