Relationship Between Time From Diagnosis and Morbidity/Mortality in Pulmonary Arterial Hypertension

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 the GRIPHON study, the largest randomized controlled trial for 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 and mortality events and response to selexipag treatment in patients with PAH? STUDY DESIGN AND METHODS The GRIPHON study randomly assigned 1,156 patients with PAH to selexipag or placebo treatment. 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 the primary end point of morbidity and 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 and 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 and 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% CI, 0.33-0.63] and 0.74 [95% CI, 0.57-0.96], respectively; P = .0219 for interaction). INTERPRETATION In the GRIPHON study, newly diagnosed PAH patients 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. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT01106014; URL:www.clinicaltrials.gov.