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Adding Selexipag to Standard Therapy Reduces Hospitalizations in Patients With Pulmonary Arterial Hypertension

Adding oral selexipag to double oral therapy (DOT) within 6 months significantly reduces the risk of hospitalization and disease progression in patients with pulmonary arterial hypertension (PAH), according to a study published in JAMA Network Open.

PAH is a rare and life-threatening condition that often leads to right heart failure. Current guidelines recommend DOT, combining an endothelin receptor antagonist (ERA) and a phosphodiesterase type 5 inhibitor (PDE5i), as the standard treatment for patients at low to intermediate risk. However, for patients whose disease progresses, the addition of selexipag, a selective prostacyclin receptor agonist, as a triple oral therapy (TOT) may provide additional benefits.

“In this study, we used a fit-for-purpose target trial framework with data from a large claims database in the US to study the comparative effectiveness of TOT that allows the delayed addition of oral selexipag vs DOT consisting of ERA and PDE5i,” wrote Charles Burger, MD, Division of Pulmonary, Allergy and Sleep Medicine, Department of Internal Medicine, Mayo Clinic in Jacksonville, Florida, and coauthors.

The researchers analyzed data from 2966 patients with PAH who had been stabilized on DOT for at least 60 days. Of these, 351 patients transitioned to TOT by adding selexipag within 6 months. Adjusted analyses revealed that TOT reduced the risk of all-cause hospitalization by 18% (aHR, 0.82; 95% CI, 0.72-0.94) compared with DOT. Similarly, TOT lowered the hazards for PAH-related hospitalizations (aHR, 0.81; 95% CI, 0.70-0.95) and disease progression (aHR, 0.82; 95% CI, 0.70-0.95).

Sensitivity analyses suggested that adding selexipag even earlier, within 3 months, might offer greater benefits (aHR, 0.77; 95% CI, 0.63-0.93). This earlier addition was associated with a 23% reduction in all-cause hospitalization risk.

The research also highlighted regional variations in PAH treatment, with most patients residing in the southern and western US. The most common ERA-PDE5i combination used was tadalafil-ambrisentan, followed by sildenafil-ambrisentan.

“This comparative effectiveness study emulating a hypothetical trial among 2966 commercially insured patients with PAH found lower risks of all-cause hospitalization, PAH-related hospitalization, and PAH-related disease progression when adding selexipag within 6 months or less of initiating DOT vs DOT alone,” concluded the study authors.

Reference

Burger CD, Tang W, Tsang Y, Panjabi S. Early addition of selexipag to double therapy for pulmonary arterial hypertension. JAMA Netw Open. 2024;7(9):e2434691. doi:10.1001/jamanetworkopen.2024.34691