Macitentan for pulmonary arterial hypertension related to repaired congenital heart disease: real-world UK experience. (3rd October 2022)

• Record Type: Journal Article
• Authors: Constantine, A; Condliffe, R; Clift, P; Jansen, K; Wort, S J; Moledina, S; Dimopoulos, K
• Is Part Of: European heart journal. Volume 43(2022)Supplement 2
• Publication Date: 2022-10-03
• Subjects: Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; 616.12005
• DOI: 10.1093/eurheartj/ehac544.1928
• Languages: English
• ISSNs: 0195-668X

Abstract

Abstract: Introduction: Patients with pulmonary arterial hypertension (PAH) following congenital heart disease (CHD) repair are an emerging population at increased risk of complications. Small numbers of such patients have been included in studies evaluating the efficacy of macitentan, but since obtaining a license for use in this population, limited real-world data have been published. Purpose: To describe the safety and efficacy of macitentan therapy in a population of adults with repaired PAH-CHD. Methods: We conducted a retrospective observational study of patients with repaired PAH-CHD newly started on macitentan in 2 UK specialist centres between 2014 and 2020. Clinical variables, including WHO functional class (FC), 6-minute walk (6MW) or incremental shuttle walk (ISW) distance, and EMPHASIS-10 score were recorded prior to and after initiation of macitentan therapy. Results: Overall, 49 patients were included, 63.3% female, median age 40.8 [26.7–53.7] years at initiation of macitentan therapy. Macitentan was started as part of the initial PAH therapeutic regimen in 18 (36.7%) and was an add-on to existing therapy in 31 (63.3%) patients, of whom over a third (35.5%) were switched from another endothelin receptor antagonist. At the time of therapy initiation, most patients (68.4%) were in WHO functional class (FC) III, while 26.3% were in FC II and 5.3% in FC I. Baseline 6-minute walk distance (n=31, 72.1%) was 355.0 [263.5–461.2] m and incremental shuttle walk distance (n=12, 27.9%) was 220.0 [175.0–302.5] m. EMPHASIS-10 score (n=39) was 24 [10–36]. After 12.7 [9.8–16.1] months of macitentan therapy, objective exercise capacity improved by 11.8 [−4.3–36.9]% (p=0.01). Health-related quality of life improved by at least 5 points in 41.9% of patients, but there was no significant change in quality of life score in the overall group (0.0 [−20.3–18.1]% change, p=0.78). Macitentan therapy was stopped in 4 (8.2%) patients due to an adverse event or patient choice, and 5 (10.2%) due to clinical worsening or absence of clinical improvement. At 1 year following macitentan initiation, 6 (12.2%) patients had been further escalated to triple therapy and 5 (10.2%) had died. Conclusions: Patients with repaired PAH-CHD treated with macitentan in the UK are a highly symptomatic group with limited exercise tolerance. Macitentan was well-tolerated overall and led to a significant improvement in objective exercise capacity. Funding Acknowledgement: Type of funding sources: Private grant(s) and/or Sponsorship.