Could We Maintain the Initial Efficacy of Triple Sequential Combination Therapies with Selexipag Against Progressive Deterioration Risk in Patients with Pulmonary Arterial Hypertension: Insights from a Single-Center Study?

backgroundThis study assessed the efficacy and tolerability of the oral prostacyclin receptor agonist selexipag as part of sequential triple combination therapy in patients with pulmonary arterial hypertension (PAH).

methodsThe study retrospectively analyzed 127 of 1160 PAH patients from a single-center registry who received sequential triple therapy including selexipag. Clinical, echocardiographic, and hemodynamic variables and multiparametric risk scores (MRS) were evaluated to assess changes in risk and outcomes.

resultsThe mean age was 43.2 ± 16.4 years, and 84.3% were female. Prior to selexipag initiation, Comparative Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension 2.0 risk strata were: 15% first, 31.5% second, 44.1% third, and 9.4% fourth; European Society of Cardiology/European Respiratory Society low-, intermediate-, and high-risk rates were 20.5%, 61.4%, and 18.1%, respectively. Mean REVEAL Lite 2.0 score was 6.3 ± 2.7. Maximal selexipag dosing reached 1600 μg BID in 18.1% of patients, while 64.6% remained at ≤1000 μg BID. Patients were grouped into low-, intermediate-, and high-dose cohorts. Median follow-up was 727.5 days (interquartile range (IQR) 224-985). Selexipag was discontinued in 15% of patients. Across dosing cohorts, initial improvements in functional class, 6-minute walk distance, right ventricular and pulmonary echocardiographic parameters, and MRSs during the first year attenuated thereafter, except for N-terminal pro-brain natriuretic peptide and Tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure ratio. Lower baseline REVEAL Lite 2.0 score predicted low-risk status at final assessment (P = .017). Three-year survival was 72.5%, 85.7%, and 75.1% in low-, medium-, and high-dose cohorts (P > .05). Mortality was independently predicted by baseline Swedish PAH Registry, REVEAL 2.0, REVEAL Lite 2.0, and REVEAL Echo scores.

conclusionEarlier escalation to triple therapy with selexipag may improve outcomes. Baseline risk-but not achieved selexipag dose-was associated with survival. A possible decline in treatment effect after 1 year warrants further investigation.