Treprostinil for the treatment of chronic thromboembolic pulmonary hypertension

ABSTRACT

Introduction: Parenteral treprostinil for patients with pulmonary arterial hypertension has resulted in improvement of exercise capacity, functional class, hemodynamics, and survival. Recently, a first randomized trial performed in patients with chronic thromboembolic pulmonary hypertension confirmed the efficacy of subcutaneous treprostinil in this subset of pulmonary hypertension.

Areas covered: Treprostinil sodium is a prostacyclin analog produced synthetically. Drug characteristics include potent systemic and pulmonary vasodilatory effects. Local side-effects of subcutaneous treprostinil have been an obstacle for its use. However, in contrast to other prostacyclins, treprostinil has favorable features. We performed a literature survey by searching PubMed for clinical trials published in any language, investigating medicinal treatments for CTEPH. We used the search terms ‘inoperable’, and ‘chronic thromboembolic pulmonary hypertension’ with ‘randomized clinical trial’, and have put treprostinil for CTEPH in the contest of published literature.

Expert opinion: Drugs approved for PAH have recently shown excellent efficacy in patients with non-operable CTEPH. Rather than head-to-head comparisons of drugs, combination treatments are to be expected in the near future. Furthermore, drugs will have to be tested alongside with pulmonary endarterectomy (PEA), and alongside balloon pulmonary angioplasty, a promising percutaneous mechanical treatment for CTEPH that is not suited for PEA.

KEYWORDS:

• Chronic thromboembolic pulmonary hypertension
• subcutaneous treprostinil
• balloon pulmonary angioplasty

Article highlights

• Chronic thromboembolic pulmonary hypertension is a pulmonary vascular disease condition that relies on precise imaging of pulmonary arterial segmentation, identification of typical CTEPH lesions and functional characterization of dependent vascular beds.

• Pulmonary thromboendarterectomy should be considered as first line in appropriate patients with CTEPH center evaluation or review.

• The remaining at least 50% of non-operable CTEPH patients should be treated with medical therapy as proven effective in randomized controlled trials, while BPA should be considered, with and without medical treatment.

• Subcutaneous treprostinil sodium has shown excellent efficacy and safety in a recently published randomized trial.

• Randomized data are currently lacking on combination of medical therapies with BPA.

• Preliminary data suggest that upfront combination treatments are more effective than monotherapy.

• Preliminary data suggest that addition of subcutaneous treprostinil in CTEPH patients undergoing BPA improves hemodynamics.

• Preliminary data suggest that medical treatments mainly increase cardiac output, while BPA is also able to lower mean pulmonary arterial pressure.

Declaration of interest

R Sadushi-Kolici has relationships with drug companies including Actelion, AOP Orphan Pharmaceuticals Bayer-Schering, GlaxoSmithKline, and SciPharm Sàrl. In addition, R Sadushi-Kolici is an investigator in trials involving these companies, relationships include consultancy service, and research grants, outside the submitted work. I Lang has relationships with drug companies including Actelion, AOP Orphan Pharmaceuticals, Astra-Zeneca, Bayer-Schering, Cordis, Daiichi-Sankyo, Ferrer, GSK, Medtronic SciPharm Sàrl, and Servier. In addition, I Lang is investigator in trials involving these companies, relationships including consultancy service, research grants, and membership of scientific advisory boards. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer dislcosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.