title: Long-term treatment, tolerability, and survival with sub-cutaneous treprostinil for severe pulmonary hypertension.
abstract: BACKGROUND
  Randomized controlled trials have resulted in improved outcomes in pulmonary arterial hypertension; however, they are biased by stringent inclusion criteria, pre-specified patient sub-sets, and study durations. In addition, common practice is to start oral therapies ahead of the more potent and titratable prostanoid therapies, despite advanced disease states at diagnosis. The objectives of our prospective registry were to evaluate long-term effects on functional class, 6-minute walking distance, hemodynamics, and survival, and also long-term tolerability of first-line sub-cutaneous treprostinil, a prostacyclin analog, in patients with severe pulmonary hypertension.
  
  
  METHODS
  Data were collected from patients with functional class III/IV pre-capillary pulmonary hypertension (Dana Point groups 1 and 4; mean right arterial pressure ≥ 10 mmHg, and/or cardiac index ≤ 2.2 liters/min/m(2)). Treprostinil dose adjustments were driven by clinical symptoms and side effects.
  
  
  RESULTS
  The study included 111 patients (1999 to 2010). Of these, 13 (12%) stopped treatment prematurely because of drug side effects, 11 (9.9%) underwent double lung transplantation, and 49 (44.1%) died of any cause (41 on treatment, 8 after early drug discontinuation). Overall survival rates at 1, 5, and 9 years were 84%, 53%, and 33%. In patients who were able to tolerate treatment > 6 months, survival rates were 57% at 9 years.
  
  
  CONCLUSIONS
  First-line treatment of severe pre-capillary pulmonary hypertension with sub-cutaneous treprostinil is safe and efficacious over many years. If up-titration beyond 6 months is tolerated, effective doses are reached and outcomes are good.
authors.affiliation: Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Roela
authors.initials: R
authors.lastname: Sadushi-Koliçi
authors.forename: Nika
authors.initials: N
authors.lastname: Skoro-Sajer
authors.forename: Daniel
authors.initials: D
authors.lastname: Zimmer
authors.forename: Diana
authors.initials: D
authors.lastname: Bonderman
authors.forename: Michael
authors.initials: M
authors.lastname: Schemper
authors.forename: Walter
authors.initials: W
authors.lastname: Klepetko
authors.forename: Jutta
authors.initials: J
authors.lastname: Glatz
authors.forename: Johannes
authors.initials: J
authors.lastname: Jakowitsch
authors.forename: Irene M
authors.initials: IM
authors.lastname: Lang
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D017079:Exercise Tolerance / Q000187:drug effects / Q000502:physiology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000401:mortality* / Q000503:physiopathology; D007279:Injections, Subcutaneous; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D011446:Prospective Studies; D012042:Registries; D012189:Retrospective Studies; D012720:Severity of Illness Index; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D011464:Epoprostenol; C427248:treprostinil