Targeting the Prostacyclin Pathway with Selexipag in Patients with Pulmonary Arterial Hypertension Receiving Double Combination Therapy: Insights from the Randomized Controlled GRIPHON Study

Figures

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  Fig. 1. Effect of selexipag on the primary composite endpoint of morbidity/mortality up to the end of treatment in patients receiving double combination therapy (with an ERA and PDE-5i) at baseline a overall, b with WHO FC II symptoms at baseline, and c with WHO FC III symptoms at baseline. Kaplan–Meier curves for the primary composite endpoint of morbidity/mortality up to the end of treatment (defined for each patient as 7 days after the date of the last intake of selexipag or placebo) in the selexipag and placebo groups. The hazard ratio (95% confidence interval) for selexipag vs. placebo was 0.63 (0.44–0.90) in the overall group, 0.36 (0.14–0.91) in patients with WHO FC II symptoms, and 0.74 (0.50–1.10) in patients with WHO FC III symptoms. Following adjustment for baseline 6MWD, the hazard ratio (95% confidence interval) was 0.37 (0.15–0.95) in patients with WHO FC II symptoms and 0.67 (0.45–1.01) in patients with WHO FC III symptoms. The analysis considered all available data; the Kaplan–Meier curve is truncated at 30 months because less than 10% of patients are at risk from this time-point onward. 6MWD 6-min walk distance, ERA endothelin receptor antagonist, PDE-5i…

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  Fig. 2. Forest plot of time to event endpoints in patients receiving double combination therapya at baseline treated with selexipag vs. placebo. Hazard ratios and confidence intervals are unadjusted estimates. aReceiving an endothelin receptor antagonist and phosphodiesterase-5 inhibitor. bThe consistency of the treatment effect across subgroups was assessed using a test for interaction. An interaction p value > 0.01 indicates no heterogeneity and that the treatment effect is likely to be consistent across subgroups. cThe solid vertical line references the overall treatment effect, and the dotted vertical line represents a hazard ratio of 1. dTreatment period defined for each patient as 7 days after last intake of selexipag or placebo. eIncludes six patients with WHO FC IV symptoms at baseline. fHazard ratio and 95% CI not shown as there were too few events to perform meaningful statistical comparisons. CI confidence interval, PAH pulmonary arterial hypertension, WHO FC World Health Organization functional class