Pulmonary Arterial Hypertension-Related Morbidity Is Prognostic for Mortality

J Am Coll Cardiol. 2018 Feb 20;71(7):752-763. doi: 10.1016/j.jacc.2017.12.010.


Background: Registry data suggest that disease progression in pulmonary arterial hypertension (PAH) is indicative of poor prognosis. However, the prognostic relevance of PAH-related morbidity has not been formally evaluated in randomized controlled trials.

Objectives: The purpose of these analyses was to assess the impact of morbidity events on the risk of subsequent mortality using the landmark method and data from the SERAPHIN and GRIPHON studies.

Methods: For each study, the risk of all-cause death up to the end of the study was assessed from the landmark time point (months 3, 6, and 12) according to whether a patient had experienced a primary endpoint morbidity event before the landmark. Each analysis was conducted using data from all patients who were available for survival follow-up at the landmark.

Results: In the SERAPHIN study, on the basis of the 3-month landmark time point, patients who experienced a morbidity event before month 3 had an increased risk of death compared with patients who did not (hazard ratio [HR]: 3.39; 95% confidence interval [CI]: 1.94 to 5.92). In the GRIPHON study, on the basis of the 3-month landmark time point, there was also an increased risk with a HR of 4.48; (95% CI: 2.98 to 6.73). Analyses based on 6-month and 12-month landmarks also showed increased risk in patients who experienced morbidity events, albeit with a reduced HR.

Conclusions: These results demonstrate the prognostic relevance of PAH-related morbidity as defined in the SERAPHIN and GRIPHON studies, highlighting the importance of preventing disease progression in patients with PAH and supporting the clinical relevance of SERAPHIN and GRIPHON morbidity events. (Study of Macitentan [ACT-064992] on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertension [SERAPHIN]; NCT00660179; Selexipag [ACT-293987] in Pulmonary Arterial Hypertension [GRIPHON]; NCT01106014).

Keywords: GRIPHON; SERAPHIN; disease progression; landmark analysis; survival.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Hypertension, Pulmonary / diagnosis*
  • Hypertension, Pulmonary / mortality*
  • Hypertension, Pulmonary / physiopathology
  • Male
  • Middle Aged
  • Morbidity
  • Mortality / trends
  • Prognosis
  • Survival Rate / trends

Associated data

  • ClinicalTrials.gov/NCT00660179
  • ClinicalTrials.gov/NCT01106014