title: Outcome of patients with severe PH due to lung disease with and without targeted therapy.
abstract: BACKGROUND
  Pulmonary hypertension (PH) can occur in patients with lung disease and worsen prognosis. Endothelin receptor antagonists, phosphodiesterase 5-inhibitors, and prostacyclin analogs, referred to as targeted therapy, have not been shown in a limited number of controlled clinical studies to improve exercise capacity in these patients. Possibly targeted therapy could be of benefit in patients with severe PH due to lung disease, but this subgroup is not well studied.
  
  
  OBJECTIVE
  To analyze influence of PH severity and use of targeted therapy on exercise capacity and survival in patients with PH due to lung disease.
  
  
  METHODS
  Consecutive patients with PH (mean pulmonary artery pressure ≥25 mmHg at rest) due to lung disease diagnosed by right heart catheterization between 1/2005 and 9/2011 were retrospectively included. Severe PH was defined as mean pulmonary artery pressure ≥35 mmHg. Patients were followed until 4/2012 for exercise capacity, survival, and targeted therapy use.
  
  
  RESULTS
  Patients with severe PH (n = 40) received significantly more often targeted therapy compared to the 32 patients with less severe PH (65% vs. 25%, P = 0.001). Survival was not significantly different between these groups (P = 0.310). Patients on targeted therapy were older, more often female, and had worse hemodynamic impairment, but significantly higher estimated 1-, 3-, and 5-year survival rates compared to untreated patients (97%, 81%, and 75% vs. 83%, 54%, and 19%, respectively; P = 0.002). This effect was mainly driven by the patients with severe PH, in whom the survival advantage was statistically significant on subgroup analysis (HR 0.182, P = 0.002). Exercise capacity was not significantly altered in any patient group.
  
  
  CONCLUSIONS
  Patients with severe PH due to lung disease may have a survival benefit from targeted therapy compared to untreated patients with less severe PH. Prospective clinical trials utilizing targeted therapy and long-term endpoints are justified in this patient group.
authors.affiliation: Department of Internal Medicine II, Division of Pneumology, University Medical Center Regensburg, Regensburg, Germany.
authors.forename: Tobias J
authors.initials: TJ
authors.lastname: Lange
authors.forename: Miriam
authors.initials: M
authors.lastname: Baron
authors.forename: Isabella
authors.initials: I
authors.lastname: Seiler
authors.forename: Michael
authors.initials: M
authors.lastname: Arzt
authors.forename: Michael
authors.initials: M
authors.lastname: Pfeifer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003937:Diagnosis, Differential; D015444:Exercise; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D008171:Lung Diseases / Q000150:complications*; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use; D016016:Proportional Hazards Models; D012189:Retrospective Studies
chemical_list: D058986:Phosphodiesterase 5 Inhibitors
keywords: Lung disease; Pulmonary hypertension; Survival; Targeted therapy