Imatinib mesylate as add-on therapy for pulmonary arterial hypertension: results of the randomized IMPRES study.

Academic Article

Abstract

  • BACKGROUND: By its inhibitory effect on platelet-derived growth factor signaling, imatinib could be efficacious in treating patients with pulmonary arterial hypertension (PAH). METHODS AND RESULTS: Imatinib in Pulmonary Arterial Hypertension, a Randomized, Efficacy Study (IMPRES), a randomized, double-blind, placebo-controlled 24-week trial, evaluated imatinib in patients with pulmonary vascular resistance ≥ 800 dyne·s·cm(-5) symptomatic on ≥ 2 PAH therapies. The primary outcome was change in 6-minute walk distance. Secondary outcomes included changes in hemodynamics, functional class, serum levels of N-terminal brain natriuretic peptide, and time to clinical worsening. After completion of the core study, patients could enter an open-label long-term extension study. Of 202 patients enrolled, 41% patients received 3 PAH therapies, with the remainder on 2 therapies. After 24 weeks, the mean placebo-corrected treatment effect on 6-minute walk distance was 32 m (95% confidence interval, 12-52; P=0.002), an effect maintained in the extension study in patients remaining on imatinib. Pulmonary vascular resistance decreased by 379 dyne·s·cm(-5) (95% confidence interval, -502 to - 255; P<0.001, between-group difference). Functional class, time to clinical worsening, and mortality did not differ between treatments. Serious adverse events and discontinuations were more frequent with imatinib than placebo (44% versus 30% and 33% versus 18%, respectively). Subdural hematoma occurred in 8 patients (2 in the core study, 6 in the extension) receiving imatinib and anticoagulation. CONCLUSIONS: Imatinib improved exercise capacity and hemodynamics in patients with advanced PAH, but serious adverse events and study drug discontinuations were common. Further studies are needed to investigate the long-term safety and efficacy of imatinib in patients with PAH. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00902174 (core study); NCT01392495 (extension).
  • Authors

    Published In

  • Circulation  Journal
  • Keywords

  • Adolescent, Adult, Aged, Benzamides, Double-Blind Method, Exercise Tolerance, Familial Primary Pulmonary Hypertension, Female, Hematoma, Subdural, Humans, Hypertension, Pulmonary, Imatinib Mesylate, Male, Middle Aged, Piperazines, Protein Kinase Inhibitors, Pyrimidines, Young Adult
  • Digital Object Identifier (doi)

    Author List

  • Hoeper MM; Barst RJ; Bourge RC; Feldman J; Frost AE; Galié N; Gómez-Sánchez MA; Grimminger F; Grünig E; Hassoun PM
  • Start Page

  • 1128
  • End Page

  • 1138
  • Volume

  • 127
  • Issue

  • 10