Selexipag in triple sequential therapy improved PAH outcomes for 12 months with no survival difference across doses; mortality related to baseline risk scores, not selexipag dose.
Does selexipag as part of triple sequential combination therapy improve clinical, hemodynamic, and survival outcomes in patients with pulmonary arterial hypertension?
In patients with PAH, triple sequential combination therapy with selexipag provides initial clinical and hemodynamic improvements that attenuate after 12 months, with long-term mortality predicted by baseline risk scores rather than the achieved selexipag dose.
Absolute Event Rate: 0% vs 0%
Abstract Background and aims In this study, we evaluated the efficacy and tolerability of oral IP receptor agonist selexipag in triple sequential combination therapies for patients with pulmonary arterial hypertension (PAH). Methods The study included 128 out of the 1160 patients with PAH enrolled in our single-center study and treated with sequential triple combinations with selexipag. Clinical, echocardiographic and hemodynamic measures, and multiparametric risk scores (MRC) were used for risk predictions. Results Age was 43.1±16.4 years and 84.4% of patients were female. Before addition of selexipag on background therapies, COMPERA 2.0 1st, 2nd, 3rd and 4th risk strata were noted in 14.8 %, 32%, 43.8% and 9.4% of patients, and ESC/ERS low, intermediate and high-risk status were noted in 20.3%, 61.7% and 18% patients, respectively. REVEAL Lite 2.0 score was and 6.3+2.7. Maximally tolerable selexipag doses (ug) were 1600 bid in 21%, 1400 bid in 6.3%, 1200 bid in 11%, equal and under 1000 bid in 64.7%. Median and mean follow-up periods were 727.5 (IQR 642.9-812.1) and 691±488.1 days, respectively. Discontinuation rates of selexipag was 14.8 %. Patients were divided into three groups based on selexipag doses: 200-400 mcg, 600-1000 mcg, and 1200-1600 mcg. Regardless of the selexipag dose status, progressive improvements in FC, 6MWD, and echocardiographic measures of pulmonary and right ventricular hemodynamics, and MRCs along the 12 months of selexipag treatments were found to be uniformly attenuated thereafter, except Nt-pro-BNP and TAPSE/PASP ratio. There was no difference in survival estimates for 1st and 3rd year across the 3 different dose groups (Figure). In different multivariable models, mortality was associated with baseline SPAHR (HR: 6.41; 2.49-16.49, p0.001), REVEAL 2.0 (HR: 1.22; 1.03-1.46, p=0.024), REVEAL lite 2.0 score (HR:1.48; 1.25-1.75, p0.001), but not with selexipag doses or other MRCs at baseline or first 6-month control. Conclusions Our results seem to be consistent with efficacy and tolerability of selexipag-including triple sequential combinations in PAH. Baseline SPAHR, REVEAL 2.0, REVEAL lite 2.0 risk status, but not selexipag doses attained, seem to be associated with mortality. However, a trend for the attenuation in the efficacy after first year of selexipag should also be taken into consideration.Survival Plot-Dose Cox regression-Dose
Tokgoz et al. (Sat,) reported a other. Selexipag in triple sequential therapy improved PAH outcomes for 12 months with no survival difference across doses; mortality related to baseline risk scores, not selexipag dose.