title: Prognosis and response to first-line single and combination therapy in pulmonary arterial hypertension.
abstract: OBJECTIVE
  To investigate survival, treatment escalation, effects of first-line single- and first-line combination therapy and prognostic markers in idiopathic- (IPAH), hereditary- (HPAH) and connective tissue disease-associated (CTD-PAH) pulmonary arterial hypertension (PAH).
  
  
  METHODS
  Retrospective analysis of medical journals from PAH patients at Skåne University Hospital 2000-2011.
  
  
  RESULTS
  1-, 2- and 3-year survival was 87%, 67%, and 54%, respectively, for the entire population, but worse (p = 0.003) in CTD-PAH than IPAH/HPAH. After 1, 2 and 3 years, 58%, 41% and 24% of patients starting on single therapy were alive on single therapy. 37.5% of patients on first-line single therapy received escalated treatment at first follow-up. First-line combination therapy more greatly decreased pulmonary vascular resistance index (PVRI, p = 0.017) than first-line single therapy. Only first-line combination therapy improved (p = 0.042) cardiac index (CI). Higher mean right atrial pressure (MRAP, p = 0.018), MRAP/CI (p = 0.021) and WHO functional class (p < 0.001) and lower 6-min walking distance (6MWD, p = 0.001) at baseline, and higher PVRI (p = 0.008) and lower 6MWD (p = 0.004) at follow-up were associated with worse outcome.
  
  
  CONCLUSIONS
  We confirm improved survival with PAH-targeted therapies. Survival is still poor and early treatment escalation frequently needed. First-line combination therapy may more potently improve haemodynamics. MRAP/CI may represent a new prognostic marker in PAH.
authors.affiliation: Department of Cardiology, Clinical Sciences, Faculty of Medicine, Lund University , Lund , Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Kylhammar
authors.forename: Liselotte
authors.initials: L
authors.lastname: Persson
authors.forename: Roger
authors.initials: R
authors.lastname: Hesselstrand
authors.forename: Göran
authors.initials: G
authors.lastname: Rådegran
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D062186:Arterial Pressure / Q000187:drug effects*; D016280:Atrial Function, Right / Q000187:drug effects; D062185:Atrial Pressure / Q000187:drug effects; D004359:Drug Therapy, Combination; D017079:Exercise Tolerance / Q000187:drug effects; D065627:Familial Primary Pulmonary Hypertension / Q000188:drug therapy / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000503:physiopathology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011651:Pulmonary Artery / Q000187:drug effects* / Q000503:physiopathology; D020127:Recovery of Function; D012189:Retrospective Studies; D013548:Sweden; D013997:Time Factors; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents
keywords: combination therapy; human; prognosis; pulmonary arterial hypertension; survival