Relationship Between Time From Diagnosis and Morbidity/Mortality in Pulmonary Arterial Hypertension: Results From the Phase III GRIPHON Study

Chest. 2021 Jul;160(1):277-286. doi: 10.1016/j.chest.2021.01.066. Epub 2021 Feb 3.

Abstract

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 Prostacyclin (PGI2) Receptor Agonist In Pulmonary Arterial Hypertension (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/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/mortality 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% 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.

Keywords: pulmonary arterial hypertension; selexipag; time from diagnosis.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / therapeutic use*
  • Adult
  • Antihypertensive Agents / therapeutic use
  • Disease Progression
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Global Health
  • Humans
  • Male
  • Middle Aged
  • Morbidity / trends
  • Prognosis
  • Pulmonary Arterial Hypertension / diagnosis*
  • Pulmonary Arterial Hypertension / drug therapy
  • Pulmonary Arterial Hypertension / epidemiology
  • Pulmonary Wedge Pressure / drug effects
  • Pulmonary Wedge Pressure / physiology*
  • Pyrazines / therapeutic use*
  • Survival Rate / trends

Substances

  • Acetamides
  • Antihypertensive Agents
  • Pyrazines
  • selexipag

Associated data

  • ClinicalTrials.gov/NCT01106014