The use of pulmonary arterial hypertension therapies in Eisenmenger syndrome

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.