Looking to the future: a new decade of pulmonary arterial hypertension therapy

Abstract

Pulmonary arterial hypertension (PAH) is a severe and debilitating disease characterised by vascular proliferation and remodelling of the small pulmonary arteries, leading to a progressive increase in pulmonary vascular resistance, increased afterload on the right ventricle and, ultimately, right heart failure. Although there is no "cure" for PAH, the availability of targeted therapies over the past decade has led to major advances in the management of PAH, reflected in improvements in survival in the modern treatment era. However, despite this, disease progression is inevitable in the majority of patients with PAH and overall the long-term prognosis, although improved, remains poor. There is a clear and urgent need for new therapeutic options, either through the development of improved drugs that act on targets established by existing PAH-specific therapies, or of agents targeting novel pathogenic pathways not addressed by currently available therapies. A number of such new agents that have shown promise in experimental models and preliminary human studies are discussed in this article.

Figure 1.

Definition of a morbidity/mortality event: primary end-point used in the SERAPHIN trial. PAH: pulmonary arterial hypertension; 6MWD: 6-min walk distance; WHO FC: World Health Organization functional class; RHF: right heart failure; PDE-5i: phosphodiesterase-5 inhibitor; ERA: endothelin receptor antagonist.

Figure 2.

Change in pulmonary vascular resistance (PVR) from baseline to week 17 in a randomised, placebo-controlled phase II trial of selexipag in patients with pulmonary arterial hypertension. Data are presented as geometric means with 95% confidence intervals. ^#: Wilcoxon rank sum test. Reproduced from [37] with permission from the publisher.