Patients With PAH Can Safely Transition From Bosentan and Sildenafil to Alternative Therapy

April 21, 2021
Laura Joszt, MA
Laura Joszt, MA

Laura is the editorial director of The American Journal of Managed Care® (AJMC®) and all its brands, including The American Journal of Accountable Care®, Evidence-Based Oncology™, and The Center for Biosimilars®. She has been working on AJMC® since 2014 and has been with AJMC®'s parent company, MJH Life Sciences, since 2011. She has an MA in business and economic reporting from New York University.

While bosentan and sildenafil is a common combination therapy in patients with pulmonary arterial hypertension (PAH), patients may need to transition to alternative therapy because of the potential for drug-drug interactions with this combination.

Patients with pulmonary arterial hypertension (PAH) treated with bosentan and sildenafil may experience drug interactions, resulting in the transition to an alternative therapy.

Guidelines recommend combination therapy with an endothelin receptor antagonist and a phosphodiesterase type 5 inhibitor, and the combination of bosentan and sildenafil has been commonly used.

“For patients already receiving the combination of bosentan and sildenafil, transitioning to alternative medications may be warranted to avoid this drug interaction and therefore improve efficacy of combination therapy,” the authors explained.

The purpose of this retrospective study, published in Pulmonary Circulation, was to assess the safety and efficacy of transitioning patients on bosentan and sildenafil to an alternative therapy. The researchers looked at adult patients with PAH taking the combination who transitioned in the Allegheny General Hospital Pulmonary Hypertension Clinic between January 2010 and February 2019.

A total of 16 patients were included in the analysis. The majority of the patients were female and had idiopathic PAH with a mean age of 57.4 years. The drug interaction between bosentan and sildenafil was the reason 43.8% of patients transitioned to a new therapy. Other reasons included adherence (n = 2), reduce monitoring (n = 4), and clinical worsening (n =1).

In 13 patients, only 1 medication was changed. Most commonly, bosentan was change to macitentan (n = 8), followed by bosentan to ambrisentan (n = 2), sildenafil to tadalafil (n = 2), and sildenafil to riociguat (n = 1). Only 3 patients had both therapies changed simultaneously: one patient changed to macitentan and tadalafil, one changed to ambrisentan and tadalafil, and one changed to ambrisentan and riociguat.

Nearly all patients (93.8%, 15/16) tolerated the transition. Although 4 patients experienced at least 1 adverse event (AE), most AEs reported during the transition were mild.

Eleven patients had information on 6-minute walk distance at baseline and after transition, but there was no significant difference. The median change was + 8 meters. All of the patients had stable or improved World Health Organization function class after their transition, and there were no significant changes in hemodynamics, N-terminal pro-brain natriuretic peptide values, or Registry to Evaluate Early and Long-Term PAH Disease Management risk scores.

The authors highlighted that the small, retrospective nature of the study was one limitation, as was the lack of a comparator group. In addition, this study did not assess long-term follow-up. Despite these limitations, they believe the study “provides meaningful information” of transitioning therapy in the real-world setting.

“Additional studies are needed to determine if this transition is associated with any improvement in clinical outcomes or hemodynamics,” the authors concluded.

Reference

Verlinden NJ, Benza RL, Raina A. Safety and efficacy of transitioning from the combination of bosentan and sildenafil to alternative therapy in patients with pulmonary arterial hypertension. Pulm Circ. 2020;10(4):2045894020945523. doi:10.1177/2045894020945523