Pulmonary arterial hypertension: tailoring treatment to risk in the current era

Abstract

Recent advances in the treatment of pulmonary arterial hypertension (PAH) have led to improved patient outcomes. Multiple PAH therapies are now available and optimising the use of these drugs in clinical practice is vital. In this review, we discuss the management of PAH patients in the context of current treatment guidelines and supporting clinical evidence. In clinical practice, considerable emphasis is placed on the importance of making treatment decisions guided by each patient's risk status, which should be assessed using multiple prognostic parameters. As PAH is a progressive disease, regular assessments are essential to ensure that any change in risk is detected in a timely manner and treatment is adjusted accordingly. With the availability of therapies that target three different pathogenic pathways, combination therapy is now the standard of care. For most patients, this involves dual combination therapy with agents targeting the endothelin and nitric oxide pathways. Therapies targeting the prostacyclin pathway should be added for patients receiving dual combination therapy who do not achieve a low-risk status. There is also a need for a holistic approach to treatment beyond pharmacological therapies. Implementation of all these approaches will ensure that PAH patients receive maximal benefit from currently available therapies.

FIGURE 1

Timeline of approval of therapies for pulmonary arterial hypertension. Therapies that are approved in the USA and/or European Union (EU) are included, positioned on the timeline based on the first date of their approval in either USA [–4] or EU [5]. Therapies are administered orally unless otherwise indicated. ERA: endothelin receptor antagonist; PDE-5i: phosphodiesterase-5 inhibitor; sGC: soluble guanylate cyclase; inh: inhaled. ^#: not approved in the EU.

FIGURE 2

Disease progression is preceded by right ventricular remodelling, but not by changes in clinical parameters. Changes in a) 6-min walking distance (6MWD), b) World Health Organization functional class (WHO FC), c) right ventricular (RV) end-diastolic volume and d) RV ejection fraction were assessed over a 10-year period for patients who were alive and transplant-free 10 years after inclusion in the study (favourable outcome, n=12) and for patients who died or required lung transplantation between 5 and 10 years after inclusion in the study (unfavourable outcome, n=10). Data are presented as mean±sem. *: p<0.05; **: p<0.01; ***: p<0.001 between groups. Reproduced and modified from [20] with permission.

FIGURE 3

Initial management of pulmonary arterial hypertension in the current era. Based on our clinical experience, the majority of patients in the low- and intermediate-risk categories should be started on dual therapy with an endothelin receptor antagonist (ERA) plus a phosphodiesterase-5 inhibitor (PDE-5i) or soluble guanylate cyclase (sGC) stimulator. A small proportion of patients in the low-risk category may be suitable for monotherapy. For all patients who are in the high-risk category, combination therapy including an i.v. prostanoid is required.