Treatment of Pulmonary Arterial Hypertension: Great Expectations!

Abstract

> “Take nothing on its looks; take everything on evidence. There’s no better rule.” > > — Charles Dickens, Great Expectations Pulmonary arterial hypertension (PAH) is a serious, progressive, often fatal condition characterized by increased pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR)1,2. Patients with PAH experience dyspnea and exercise limitation — and as right ventricular (RV) failure develops, edema, exertional chest pain, syncope, and increased risk of death. PAH is most commonly idiopathic (IPAH) or associated with an underlying connective tissue disease (CTD-PAH), such as scleroderma1. In both IPAH and CTD-PAH patients, median survival is less than 3 years in the absence of therapy3,4,5. Research advances in our understanding of the pathobiology of PAH have led to the study, approval, and availability of many novel PAH-specific medications. These include prostanoid analogs (i.e., intravenous epoprostenol, subcutaneous/intravenous treprostinil), endothelin receptor antagonists (i.e., ambrisentan, bosentan), and phosphodiesterase type-5 inhibitors (i.e., sildenafil, tadalafil)2,6. What are the expectations of this array of therapies on the part of patients with PAH and their physicians? The published evidence, typically short-term, 3 to 4-month, randomized controlled trials of all these therapies, demonstrates benefit in both IPAH and CTD-PAH7. A majority of patients have small reductions in PAP and PVR, increased cardiac output, decreased symptoms, and increased exercise capacity, as measured by 6-minute walk test (6-MWT). New York Heart Association/World Health Organization (NYHA/WHO) functional class will improve in about one-third of patients, and objectively measured quality of life (QOL) may also improve2,6,7. A metaanalysis of published randomized controlled trials of PAH-specific therapies also confirmed a small, short-term survival benefit7. Thus, based on the evidence, patients with PAH and their physicians expect symptomatic benefit and improved functional capacity, important components … Address correspondence to Dr. S. Mehta, Division of Respirology, London Health Sciences Center, Victoria Hospital, Room E1.325, 800 Commissioner’s Road East, London, ON N6A 5W9, Canada. E-mail: sanjay.mehta{at}lhsc.on.ca