Pulmonary Arterial Hypertension: Early Treatment with Selexipag Most Effective

New post-hoc analyses from the large-scale GRIPHON trial assessing selexipag in patients with pulmonary arterial hypertension (PAH) demonstrate that early, aggressive treatment after diagnosis is associated with the greatest benefits, irrespective of background therapy [1].

Around a third of PAH patients currently die within 5 years of diagnosis; early recognition and prompt treatment of the disease are key to achieving sustained long-term benefits [2]. The GRIPHON study evaluated the long-term efficacy and safety of oral selexipag in 1,156 patients with PAH across 181 centres from 39 countries. It is the largest randomised, controlled, outcome trial ever conducted in patients with PAH and generated data that is still being analysed. A 40% reduction in the primary composite endpoint of morbidity/mortality was met (i.e. disease progression, worsening of PAH resulting in hospitalisation, initiation of intravenous prostanoid therapy or long-term oxygen therapy, or the need for lung transplantation/balloon atrial septostomy, or death from any cause). Overall, the most common adverse events for patients receiving selexipag were headache, diarrhoea, nausea, and jaw pain [3].

Selexipag is an oral selective prostacyclin I2 receptor agonist, and is indicated for the treatment of PAH to delay disease progression and reduce the risk of hospitalisation. In Europe, selexipag is indicated for the long-term treatment of PAH in adult patients with WHO functional class (FC) II-III, either as combination therapy in patients insufficiently controlled with an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor, or as monotherapy in patients who are not candidates for these therapies. The GRIPHON study underscored the importance of the prostacyclin pathway in PAH.

The post-hoc analysis presented at ATS 2019 by Prof. Sean Gaine (Mater Misericordiae University Hospital, Ireland) evaluated the impact of time from diagnosis to initiation of selexipag on the treatment response with respect to the primary endpoint of the study. Patients were categorised at baseline based on their time from diagnosis using a 6-month threshold. Patients treated earlier were defined as those who received treatment ≤6 months from diagnosis (n=404), and those who were treated later received treatment >6 months from diagnosis (n=752). Selexipag reduced the risk of morbidity/mortality, compared with placebo, in both groups with a risk reduction of 55% for those treated earlier (HR 0.45 [95% CI: 0.33-0.63]) and a risk reduction of 30% for those treated later (HR 0.70 [95% CI: 0.54-0.91]). The response was more pronounced in those treated earlier. This pattern was observed in all background PAH therapy subgroups involved in the 2015 trial.

  1. Gaine SP, et al. The Impact of Time from Diagnosis at Baseline on Long-Term Outcome in the GRIPHON Study: Selexipag in Pulmonary Arterial Hypertension. A2502, ATS 2019, 17-22 May, Dallas, USA.
  2. McGoon MD et al. Pulmonary arterial hypertension: epidemiology and registries. J Am Coll Cardiol. 2013 Dec 24;62(25 Suppl):D51-9. doi: 10.1016/j.jacc.2013.10.023.
  3. Sitbon O, et al. N Engl J Med 2015;373(26):2522–33.