The use of pulmonary arterial hypertension therapies in Eisenmenger syndrome

ABSTRACT

Introduction

For many years, treatment options for patients with Eisenmenger physiology had been restricted to conservative measures to alleviate multi-system complications. The use of pulmonary arterial hypertension (PAH)-targeted therapies in patients with Eisenmenger syndrome (ES) changed the course of the disease, since they substantially improved clinical outcomes and increased survival.

Areas Covered

In this review, we primarily focus on the use of PAH pharmacotherapies in ES. A literature search was carried out in PubMed, Scopus and Cochrane Database up to May 2021. We thoroughly discuss current evidence about mechanisms of action, safety, and efficacy of these agents and present challenges and gaps in literature regarding the recommended treatment approach.

Expert Opinion

Unlike other forms of PAH, we usually treat patients with ES more conservatively as we lack evidence that aggressive management is safe and effective in this complex population. Several issues on the time of initiation of PAH-targeted therapies, choice between monotherapy vs. upfront combination therapy, and time of escalation still remain challenging and require further investigation. Therapeutic management should be guided by patients’ individual evaluation based on available prognostic markers. More well-designed trials are warranted to assess the benefits of new PAH-targeted agents and combination therapies.

KEYWORDS:

• Eisenmenger syndrome
• phosphodiesterase type-5 inhibitors
• endothelin receptor antagonists
• prostanoids
• monotherapy
• combination therapy
• risk stratification
• artificial intelligence
• randomized controlled trials

Article highlights

• In the last two decades, there has been a revolution in managing patients with Eisenmenger syndrome, with the introduction of PAH-targeted therapies that substantially improved clinical outcomes.

• Unlike other forms of PAH, in which a therapeutic risk-oriented approach has been recently adopted to guide therapeutic management, we tend to treat patients with Eisenmenger syndrome in a more conservative way, since only scarce data exist on the efficacy and safety of escalation to combination therapy compared to monotherapy in patients with ES.

• Risk stratification is challenging for patients with Eisenmenger physiology since the existing risk scores for other PAH categories could not be applied in this complex population.

• Careful individual evaluation should take place using the existing prognostic markers as risk stratification tools to guide clinical decisions.

• Artificial intelligence may have a great impact on the prognostication and risk stratification in patients with Eisenmenger syndrome.

• More well-designed clinical trials are warranted to assess the benefits of new PAH-targeted agents and combination therapies.

Abbreviations

 

Acknowledgments

GP Diller would like to acknowledge funding by the Karla Völlm Foundation, supporting research in the Department.

Declaration of Interest

A Arvanitaki is the recipient of the International Training and Research Fellowship EMAH Stiftung Karla Voellm, Krefeld, Germany. GP Diller has received funding from Actelion/ Janssen Pharmaceuticals, Daiichi Sankyo, and Bayer, previously, unrelated to the current work. 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 disclosures

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

Additional information

Funding

This paper was not funded.