Long-Term Experience with Epoprostenol

Epoprostenol is the formal name for synthetic prostacyclin, ordinarily delivered via continuous intravenous infusion through a surgically-implanted indwelling central venous line.  Epoprostenol has been shown to extend the survival of all New York Heart Association Class III and IV patients, on average.  A study by V. McLaughlin of Rush Medical College in Chicago showed that regardless of a patient’s risk factors for death from pulmonary hypertension, there were less deaths than expected in the first year of therapy if the patients were placed on epoprostenol.  Dr. McLaughlin divided 108 patients with PPH into ten different deciles of mortality risk based on National Institutes of Health criteria.  In every decile group, the deaths observed after one year of epoprostenol therapy were less than the expected number of deaths.

Similar results have been shown in pulmonary hypertension secondary to system sclerosis by separate team of researchers at Colorado Health Sciences Center and the Pulmonology Center at Boston University School of Medicine.  In these studies, reported at the 2000 meeting of the American Thoracic Society, survival of patients with this condition was increased from 45%-55% at one year for untreated patients.  The Colorado Health Sciences study showed survival of 70% after one year of epoprostenol treatment and 80% if the epoprostenol treatment coincided with the one year anniversary of diagnosis.  The Boston University study showed increased survival as compared to predicted untreated survival up to three years after commencement of epoprostenol infusion.

With enhanced long-term survival now possible via epoprostenol infusion for pulmonary hypertension patients, it becomes more important to focus on long-term dosing strategy as well as lung transplantation referral timing.  In separate year 2000 American Thoracic Society abstracts, Dr. McLaughlin reported on research showing that 22 to 45 ng/kg/min was the optimal long-term epoprostenol dose range, and that referral for lung transplantation is not necessary for patients who are NYHA Function Class (FC) I or II after a year of epoprostenol therapy.  Epoprostenol doses above 45 ng/kg/min produced excess toxicity without therapeutic benefit.  This finding is significant given the high cost of epoprostenol.  If a patient is not resonding at this dose level, they need to be referred for lung transplantation.  Indeed, patients who are FC upon epoprostenol initiation should be listed for transplantation given the long waitlists, and patients who are FC III after a year of therapy should be strongly considered for transplantation, notwithstanding an overall favorable prognosis for this group with extended epoprostenol therapy.