Risk stratification and medical therapy of pulmonary arterial hypertension

Abstract

Pulmonary arterial hypertension (PAH) remains a severe clinical condition despite the availability over the past 15 years of multiple drugs interfering with the endothelin, nitric oxide and prostacyclin pathways. The recent progress observed in medical therapy of PAH is not, therefore, related to the discovery of new pathways, but to the development of new strategies for combination therapy and on escalation of treatments based on systematic assessment of clinical response. The current treatment strategy is based on the severity of the newly diagnosed PAH patient as assessed by a multiparametric risk stratification approach. Clinical, exercise, right ventricular function and haemodynamic parameters are combined to define a low-, intermediate- or high-risk status according to the expected 1-year mortality. The current treatment algorithm provides the most appropriate initial strategy, including monotherapy, or double or triple combination therapy. Further treatment escalation is required in case low-risk status is not achieved in planned follow-up assessments. Lung transplantation may be required in most advanced cases on maximal medical therapy.

Intravenous treprostinil as an add-on therapy in patients with pulmonary arterial hypertension

“…Current guidelines recommend an individualized risk-based approach. 4,5,7 Risk is determined by a set of clinical, laboratory, and hemodynamic variables that can be used at any time point during the course of the disease to estimate the likelihood of death (or the need for lung transplantation) over the ensuing years. The principle goal of PAH treatment is to reach a low-risk profile, which is usually accompanied by 5-year survival rates of 90% or higher.…”

“…8−11 Patients not reaching a low-risk profile have an insufficient response to therapy and require additional treatments. 4,5,7 The majority of patients with newly diagnosed PAH present with a low-or intermediate-risk profile, and most of these patients receive oral therapies, predominantly endothelin receptor antagonists and PDE5 inhibitors, either alone or in combination. 8,12 The individual response to treatment is highly variable, and follow-up evaluations are required to determine whether or not a low-risk profile has been achieved.…”

Treating Pulmonary Arterial Hypertension With Exercise: The Role of Rehabilitative Medicine

“…Using disease-targeted therapy, we can improve pulmonary artery hemodynamics and right heart function. 9 Exercise training is then needed to reverse the concomitant deconditioning and maximize the benefit to be derived from the pharmacotherapy.…”

Treatment of pediatric pulmonary arterial hypertension: A focus on the NO‐sGC‐cGMP pathway

“…Endogenous prostacyclin (prostaglandin I 2 ) activates prostacyclin receptors in pulmonary vascular smooth muscle cells and other tissues, increasing production of cyclic adenosine monophosphate, which induces pulmonary vasodilation as well as antithrombotic, antiproliferative, antimitogenic, and immunomodulatory effects . Prostacyclin levels are reduced in patients with PAH, providing a rationale for treatment with prostacyclin analogs (prostanoids) .…”