Treatment of patients with pulmonary arterial hypertension at the time of death or deterioration to functional class IV: insights from the REVEAL Registry

J Heart Lung Transplant. 2013 Nov;32(11):1114-22. doi: 10.1016/j.healun.2013.08.010. Epub 2013 Sep 10.

Abstract

Background: Current guidelines recommend intravenous prostacyclin as first-line therapy for patients with pulmonary arterial hypertension (PAH) in New York Heart Association/World Health Organization functional class (FC) IV, or combination therapy for patients in any FC who do not respond to monotherapy. We investigated the aggressiveness of therapy in patients enrolled in the REVEAL (Registry to Evaluate Early and Long-Term PAH Disease Management) Registry who deteriorated to FC IV or died.

Methods: Among 3,515 patients (age ≥ 18 years) in REVEAL with a mean pulmonary artery pressure ≥ 25 mm Hg and pulmonary capillary wedge pressure ≤ 15 mm Hg, we examined three sub-sets: the 487 patients who had a PAH-related death, the larger set of 908 patients who died from any cause (PAH-related, not PAH-related, or unknown), and the 294 patients who were FC I, II, or III at enrollment and later assessed as FC IV.

Results: Among patients who died, 56% (n = 272 of 487) and 43% (n = 391 of 908) were receiving intravenous prostacyclin before death in the PAH-related death and all-cause death cohorts, respectively. In the PAH-related death cohort, 60% and 16% of patients were most recently assessed as FC III and IV, respectively; among those assessed as FC IV within 6 months of death, 57.7% (n = 15 of 26) had received intravenous prostacyclin. Because many patients died without an observed assessment of worsening to FC IV, we also evaluated medication use among the cohort of patients who worsened to FC IV during the study. One day before worsening to FC IV, 150 of 294 patients were not receiving intravenous prostacyclin and 70 were receiving only PAH-specific monotherapy; of these, 61% and 67%, respectively, received no additional therapy 90 days later.

Conclusions: Intravenous prostacyclin and combination therapy are not consistently used in the most seriously ill patients enrolled in REVEAL after being assessed as FC IV or at the time of death.

Keywords: pharmacology; prognosis; pulmonary hypertension; registries; survival.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Administration, Inhalation
  • Administration, Intravenous
  • Administration, Oral
  • Adult
  • Aged
  • Disease Management*
  • Disease Progression*
  • Drug Therapy, Combination
  • Endothelin Receptor Antagonists*
  • Epoprostenol / administration & dosage
  • Epoprostenol / therapeutic use*
  • Familial Primary Pulmonary Hypertension
  • Female
  • Humans
  • Hypertension, Pulmonary / classification*
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / mortality
  • Infusions, Parenteral
  • Infusions, Subcutaneous
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Phosphodiesterase 5 Inhibitors / administration & dosage
  • Phosphodiesterase 5 Inhibitors / therapeutic use*
  • Pulmonary Wedge Pressure
  • Registries
  • Survival Rate

Substances

  • Endothelin Receptor Antagonists
  • Phosphodiesterase 5 Inhibitors
  • Epoprostenol