Epoprostenol for the treatment of pulmonary arterial hypertension

ABSTRACT

Introduction: Pulmonary arterial hypertension (PAH) is a rare, progressive, and severe disease. Since the first demonstration of survival benefit of intravenous epoprostenol in monotherapy in 1996, prostanoids remain the cornerstone for PAH patients at high risk. This review is essential to understand the current situation of this drug among all the therapeutic possibilities concerning this entity.

Areas covered: The aim of this article is to review the pharmacological properties of epoprostenol and to update its clinical evidence in different specific clinical scenarios. A deep literature search was carried out on the MEDLINE database for published literature before March 2021.

Expert opinion: Epoprostenol is still the best treatment option for high-risk PAH patients. Nevertheless, there are many unsolved questions: drug dosing, its use in combination therapy with other pulmonary vasodilators, and the utility in PAH associated with connective tissue disease, congenital heart disease, or pulmonary veno-occlusive disease are only a few examples. Its safety and efficacy are supported by clinical trials, observational work, and experience, both as monotherapy and in combination therapy. Epoprostenol should be considered a destination treatment in high-risk patients and not only as a bridge to pulmonary transplantation. However, it remains underused in clinical practice.

KEYWORDS:

• Epoprostenol
• prostanoids
• pulmonary arterial hypertension
• survival
• patient-centered

Article highlights

• In the last three decades, research in pulmonary arterial hypertension (PAH) has allowed the release into the market several different pulmonary vasodilators, included into three different metabolic pathways.

• One important advance was the discovery of prostanoids as a therapeutic option due to its vasodilatory, anti-inflammatory, antiaggregative, and antiproliferative effects.

• Epoprostenol was the first and a single drug that demonstrated a decrease in mortality in a clinical trial in idiopathic PAH. Guidelines recommend the use of this drug in high-risk PAH patients. Nevertheless, American and European registries demonstrate an underuse of this drug in clinical practice. Fear of common side effects and the need for a continuous intravenous line could be related with this fact.

• Combination therapy targets multiple pathways at the same time. Even though this therapeutic option has been tested and has demonstrated a clinical benefit when double oral therapy, with a phosphodiesterase-5 inhibitor and an endothelin-receptor antagonist are used, there are no clinical trials evaluating the use of epoprostenol in combination.

• Other unsolved questions regarding epoprostenol include its use in associated forms of PAH and the optimal dosage. Coordinated support of medical doctors, nurses, and patients is crucial not only to guarantee the best treatment administered to the patient but also to progress in the knowledge of this entity.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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