TY - JOUR
T1 - Selexipag for the treatment of pulmonary arterial hypertension
AU - GRIPHON Investigators
AU - Sitbon, Olivier
AU - Channick, Richard
AU - Chin, Kelly M.
AU - Frey, Aline
AU - Gaine, Sean
AU - Galiè, Nazzareno
AU - Ghofrani, Hossein Ardeschir
AU - Hoeper, Marius M.
AU - Lang, Irene M.
AU - Preiss, Ralph
AU - Rubin, Lewis J.
AU - Di Scala, Lilla
AU - Tapson, Victor
AU - Adzerikho, Igor
AU - Liu, Jinming
AU - Moiseeva, Olga
AU - Zeng, Xiaofeng
AU - Simonneau, Gérald
AU - McLaughlin, Vallerie V.
N1 - Publisher Copyright:
Copyright © 2015 Massachusetts Medical Society. All rights reserved.
PY - 2015/12/24
Y1 - 2015/12/24
N2 - Background: In a phase 2 trial, selexipag, an oral selective IP prostacyclin-receptor agonist, was shown to be beneficial in the treatment of pulmonary arterial hypertension. Methods: In this event-driven, phase 3, randomized, double-blind, placebo-controlled trial, we randomly assigned 1156 patients with pulmonary arterial hypertension to receive placebo or selexipag in individualized doses (maximum dose, 1600 μg twice daily). Patients were eligible for enrollment if they were not receiving treatment for pulmonary arterial hypertension or if they were receiving a stable dose of an endothelin-receptor antagonist, a phosphodiesterase type 5 inhibitor, or both. The primary end point was a composite of death from any cause or a complication related to pulmonary arterial hypertension up to the end of the treatment period (defined for each patient as 7 days after the date of the last intake of selexipag or placebo). Results: A primary end-point event occurred in 397 patients - 41.6% of those in the placebo group and 27.0% of those in the selexipag group (hazard ratio in the selexipag group as compared with the placebo group, 0.60; 99% confidence interval, 0.46 to 0.78; P<0.001). Disease progression and hospitalization accounted for 81.9% of the events. The effect of selexipag with respect to the primary end point was similar in the subgroup of patients who were not receiving treatment for the disease at baseline and in the subgroup of patients who were already receiving treatment at baseline (including those who were receiving a combination of two therapies). By the end of the study, 105 patients in the placebo group and 100 patients in the selexipag group had died from any cause. Overall, 7.1% of patients in the placebo group and 14.3% of patients in the selexipag group discontinued their assigned regimen prematurely because of adverse events. The most common adverse events in the selexipag group were consistent with the known side effects of prostacyclin, including headache, diarrhea, nausea, and jaw pain. Conclusions: Among patients with pulmonary arterial hypertension, the risk of the primary composite end point of death or a complication related to pulmonary arterial hypertension was significantly lower with selexipag than with placebo. There was no significant difference in mortality between the two study groups.
AB - Background: In a phase 2 trial, selexipag, an oral selective IP prostacyclin-receptor agonist, was shown to be beneficial in the treatment of pulmonary arterial hypertension. Methods: In this event-driven, phase 3, randomized, double-blind, placebo-controlled trial, we randomly assigned 1156 patients with pulmonary arterial hypertension to receive placebo or selexipag in individualized doses (maximum dose, 1600 μg twice daily). Patients were eligible for enrollment if they were not receiving treatment for pulmonary arterial hypertension or if they were receiving a stable dose of an endothelin-receptor antagonist, a phosphodiesterase type 5 inhibitor, or both. The primary end point was a composite of death from any cause or a complication related to pulmonary arterial hypertension up to the end of the treatment period (defined for each patient as 7 days after the date of the last intake of selexipag or placebo). Results: A primary end-point event occurred in 397 patients - 41.6% of those in the placebo group and 27.0% of those in the selexipag group (hazard ratio in the selexipag group as compared with the placebo group, 0.60; 99% confidence interval, 0.46 to 0.78; P<0.001). Disease progression and hospitalization accounted for 81.9% of the events. The effect of selexipag with respect to the primary end point was similar in the subgroup of patients who were not receiving treatment for the disease at baseline and in the subgroup of patients who were already receiving treatment at baseline (including those who were receiving a combination of two therapies). By the end of the study, 105 patients in the placebo group and 100 patients in the selexipag group had died from any cause. Overall, 7.1% of patients in the placebo group and 14.3% of patients in the selexipag group discontinued their assigned regimen prematurely because of adverse events. The most common adverse events in the selexipag group were consistent with the known side effects of prostacyclin, including headache, diarrhea, nausea, and jaw pain. Conclusions: Among patients with pulmonary arterial hypertension, the risk of the primary composite end point of death or a complication related to pulmonary arterial hypertension was significantly lower with selexipag than with placebo. There was no significant difference in mortality between the two study groups.
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U2 - 10.1056/NEJMoa1503184
DO - 10.1056/NEJMoa1503184
M3 - Article
C2 - 26699168
AN - SCOPUS:84951967550
SN - 0028-4793
VL - 373
SP - 2522
EP - 2533
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 26
ER -