• Ioana R Preston, Richard N Channick, Kelly Chin, Lilla Di Scala, Harrison W Farber, Sean Gaine, Nazzareno Galiè, Hossein-Ardeschir Ghofrani, Marius M Hoeper, Irene M Lang, Vallerie V McLaughlin, Ralph Preiss, Gérald Simonneau, Olivier Sitbon, Victor F Tapson, and Lewis J Rubin.
• Pulmonary, Critical Care, and Sleep Division, Tufts Medical Center, Boston, Massachusetts. Electronic address: ipreston@tuftsmedicalcenter.org.
• J. Heart Lung Transplant. 2018 Mar 1; 37 (3): 401-408.

BackgroundParenteral prostacyclin analogs that target the prostacyclin pathway have been used to treat pulmonary arterial hypertension (PAH) since the 1990s. Abrupt discontinuation of parenteral prostacyclin analogs can be associated with acute deterioration of PAH. Less is known about temporary interruption of oral therapies that target the prostacyclin pathway, such as selexipag.MethodsWe evaluated the frequency, duration, reasons, and consequences of temporary selexipag interruptions among PAH patients enrolled in the Prostacyclin (PGI2) Receptor Agonist in Pulmonary Arterial Hypertension (GRIPHON) study. In GRIPHON, patients were randomized to selexipag or placebo and titrated to an individualized highest tolerated dose (200 to 1,600 µg twice daily) over 12 weeks, after which patients entered the maintenance phase. Treatment interruptions were allowed; if the interruption was < 3 days, treatment was restarted at the previous highest tolerated dose; if the interruption was ≥ 3 days, retitration from 200 µg twice daily was required. Descriptive analyses were performed.ResultsAt least 1 treatment interruption occurred in 111 of 574 patients (19.3%) in the selexipag group and in 58 of 582 (10.0%) in the placebo group. Baseline characteristics were similar between patients with and without an interruption. Of the 111 patients in whom selexipag was temporarily interrupted, 94 (85%) were receiving background PAH therapy. Adverse events were the most common reason for selexipag interruption. Selexipag interruptions and reinstitution of treatment were well tolerated. There were no episodes of acute deterioration during treatment interruption.ConclusionsBased on observations from GRIPHON, selexipag interruptions can be expected in clinical practice. However, temporarily interrupting selexipag was well tolerated and manageable.Copyright © 2018. Published by Elsevier Inc.

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