TY - JOUR
T1 - Targeting the Prostacyclin Pathway with Selexipag in Patients with Pulmonary Arterial Hypertension Receiving Double Combination Therapy
T2 - Insights from the Randomized Controlled GRIPHON Study
AU - Coghlan, J. Gerry
AU - Channick, Richard
AU - Chin, Kelly
AU - Di Scala, Lilla
AU - Galiè, Nazzareno
AU - Ghofrani, Hossein Ardeschir
AU - Hoeper, Marius M.
AU - Lang, Irene M.
AU - McLaughlin, Vallerie
AU - Preiss, Ralph
AU - Rubin, Lewis J.
AU - Simonneau, Gérald
AU - Sitbon, Olivier
AU - Tapson, Victor F.
AU - Gaine, Sean
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2018/2/1
Y1 - 2018/2/1
N2 - Background: In pulmonary arterial hypertension (PAH), combination therapy is an important treatment strategy. Although randomized controlled trial data are available to support the combination of two therapies, data regarding triple combination therapy are few. Objective: The phase III GRIPHON trial enrolled 1156 patients with PAH, including 376 receiving background double combination therapy. We evaluated the efficacy and safety of selexipag as a third agent in these patients and further analyzed this subgroup according to symptom burden at baseline as indicated by World Health Organization (WHO) functional class (FC). Methods: In this post hoc analysis, hazard ratios (HRs) and 95% confidence intervals (CI) were calculated using Cox proportional-hazard models to determine response to selexipag versus placebo on the composite primary endpoint of morbidity/mortality. Baseline characteristics and adverse events were summarized descriptively. Results: Of 376 patients receiving background endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE-5i) therapy, 115 had WHO FC II symptoms and 255 had WHO FC III symptoms at baseline. The impact on the primary endpoint of adding selexipag versus placebo to double combination therapy was consistent with the effect in the overall population (HR 0.63; 95% CI 0.44–0.90) as well as in patients with WHO FC II and III symptoms. Compared with the overall population, discontinuations due to an adverse event were higher when selexipag was added to background double combination therapy; no safety concerns were identified. Conclusion: The addition of selexipag to background double combination therapy with an ERA and PDE-5i provides an incremental benefit similar to that seen in the overall population, including in patients with WHO FC II or III symptoms at baseline. ClinicalTrials.gov Identifier: NCT01106014.
AB - Background: In pulmonary arterial hypertension (PAH), combination therapy is an important treatment strategy. Although randomized controlled trial data are available to support the combination of two therapies, data regarding triple combination therapy are few. Objective: The phase III GRIPHON trial enrolled 1156 patients with PAH, including 376 receiving background double combination therapy. We evaluated the efficacy and safety of selexipag as a third agent in these patients and further analyzed this subgroup according to symptom burden at baseline as indicated by World Health Organization (WHO) functional class (FC). Methods: In this post hoc analysis, hazard ratios (HRs) and 95% confidence intervals (CI) were calculated using Cox proportional-hazard models to determine response to selexipag versus placebo on the composite primary endpoint of morbidity/mortality. Baseline characteristics and adverse events were summarized descriptively. Results: Of 376 patients receiving background endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE-5i) therapy, 115 had WHO FC II symptoms and 255 had WHO FC III symptoms at baseline. The impact on the primary endpoint of adding selexipag versus placebo to double combination therapy was consistent with the effect in the overall population (HR 0.63; 95% CI 0.44–0.90) as well as in patients with WHO FC II and III symptoms. Compared with the overall population, discontinuations due to an adverse event were higher when selexipag was added to background double combination therapy; no safety concerns were identified. Conclusion: The addition of selexipag to background double combination therapy with an ERA and PDE-5i provides an incremental benefit similar to that seen in the overall population, including in patients with WHO FC II or III symptoms at baseline. ClinicalTrials.gov Identifier: NCT01106014.
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U2 - 10.1007/s40256-017-0262-z
DO - 10.1007/s40256-017-0262-z
M3 - Article
C2 - 29307087
AN - SCOPUS:85040079654
SN - 1175-3277
VL - 18
SP - 37
EP - 47
JO - American Journal of Cardiovascular Drugs
JF - American Journal of Cardiovascular Drugs
IS - 1
ER -