BACKGROUND: Early initiation of pulmonary arterial hypertension (PAH) therapies is associated with improved long-term outcomes, yet data on the early use of prostacyclin pathway agents are limited. In these post hoc analyses of GRIPHON, the largest randomized controlled trial in PAH to date, the prognostic value of time from diagnosis and its impact on treatment response were examined. RESEARCH QUESTION: How does time from diagnosis impact morbidity/mortality events and response to selexipag treatment in patients with PAH? STUDY DESIGN: and Methods: GRIPHON randomly assigned 1156 patients with PAH to selexipag or placebo. Patients were categorized post hoc into a time from diagnosis of ≤ 6 months and > 6 months at randomization. Hazard ratios (selexipag vs placebo) were calculated for primary endpoint morbidity/mortality events by time from diagnosis using Cox proportional hazard models. RESULTS: Time from diagnosis was ≤ 6 months in 34.9% and > 6 months in 65.1% of patients. Time from diagnosis was prognostic of morbidity/mortality, with newly diagnosed patients having a poorer long-term outcome than patients diagnosed for longer. Compared with placebo, selexipag reduced the risk of morbidity/mortality in patients with a time from diagnosis of ≤ 6 months and > 6 months, with a more pronounced effect in newly diagnosed patients (hazard ratio 0.45 [95% confidence interval 0.33-0.63] and hazard ratio 0.74 [95% confidence interval 0.57-0.96], respectively; interaction p-value 0.0219). INTERPRETATION: In GRIPHON, PAH patients who were newly diagnosed had a worse prognosis than patients with a longer time from diagnosis. The benefit of selexipag treatment on disease progression was more pronounced in patients treated earlier than in patients treated later.
- Gaine, S.
- Sitbon, O.
- Channick, R. N.
- Chin, K. M.
- Sauter, R.
- Galiè, N.
- Hoeper, M. M.
- McLaughlin, V. V.
- Preiss, R.
- Rubin, L. J.
- Simonneau, G.
- Tapson, V.
- Ghofrani, H. A.
- Lang, I.
