title: Efficacy and Safety of Long-Term Imatinib Therapy for Pulmonary Arterial Hypertension.
abstract: BACKGROUND
  Antiproliferative strategies have emerged as a potential therapeutic option for pulmonary arterial hypertension (PAH).
  
  
  OBJECTIVE
  To evaluate the long-term efficacy and safety of imatinib.
  
  
  METHODS
  This is an observational study of 15 patients with idiopathic PAH (n = 13) or PAH associated with connective tissue disease (n = 2) treated off-label with imatinib 400 mg daily. Pulmonary hypertension-specific therapy was established in all patients (triple therapy in 10, dual therapy in 3, and monotherapy in 2 patients).
  
  
  RESULTS
  After 6 months, improvement in hemodynamics (p < 0.01), functional class (p = 0.035), and quality of life (p = 0.005) was observed. After a median follow-up of 37 months, there was a sustained improvement in functional class (p = 0.032), quality of life (p = 0.019), and echocardiographic parameters of right ventricular function (p < 0.05). Three patients (20%) presented with completely normal echocardiography, absent tricuspid regurgitation, and normal pro-brain natriuretic peptide levels, indicative of 'hemodynamic remission'. Of note, however, only 1 case was assessed by invasive hemodynamics. The overall 1- and 3-year survival was 100 and 90%, respectively. Two patients experienced a subdural hematoma (SDH), which in both cases resolved without sequelae. After careful consultation of the potential risks and benefits, all patients as well as a safety cohort of 9 subsequent cases decided to continue the imatinib therapy. After adjusting the target international normalized ratio (INR) to around 2.0, no further cases of SDH occurred during 50 patient-years.
  
  
  CONCLUSIONS
  Long-term treatment with imatinib may improve the functional class and quality of life. Single cases might even attain hemodynamic remission. The occurrence of 5% SDH per patient-years is concerning. However, adjusting the INR to around 2.0 might obviate this complication.
authors.affiliation: Pulmonary Hypertension Program, Clinic of Pneumology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Speich
authors.forename: Silvia
authors.initials: S
authors.lastname: Ulrich
authors.forename: Guido
authors.initials: G
authors.lastname: Domenighetti
authors.forename: Lars C
authors.initials: LC
authors.lastname: Huber
authors.forename: Manuel
authors.initials: M
authors.lastname: Fischler
authors.forename: Ursula
authors.initials: U
authors.lastname: Treder
authors.forename: Alexander
authors.initials: A
authors.lastname: Breitenstein
mesh_terms: D000328:Adult; D000368:Aged; D004452:Echocardiography; D005260:Female; D006408:Hematoma, Subdural / Q000139:chemically induced; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000000981:diagnostic imaging / Q000188:drug therapy*; D000068877:Imatinib Mesylate / Q000627:therapeutic use*; D019934:International Normalized Ratio; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011788:Quality of Life; D012074:Remission Induction; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate