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

Hoeper, M.M. et al. (2013) Imatinib mesylate as add-on therapy for pulmonary arterial hypertension: results of the randomized IMPRES study. Circulation, 127(10), pp. 1128-1138. (doi: 10.1161/CIRCULATIONAHA.112.000765)

Full text not currently available from Enlighten.


<p>Background—By its inhibitory effect on platelet-derived growth factor signaling, imatinib could be efficacious in treating patients with pulmonary arterial hypertension (PAH).</p> <p>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.</p> <p>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.</p>

Item Type:Articles
Glasgow Author(s) Enlighten ID:Peacock, Professor Andrew
Authors: Hoeper, M.M., Barst, R.J., Bourge, R.C., Feldman, J., Frost, A.E., Galie, N., Gomez-Sanchez, M.A., Grimminger, F., Grunig, E., Hassoun, P.M., Morrell, N.W., Peacock, A.J., Satoh, T., Simonneau, G., Tapson, V.F., Torres, F., Lawrence, D., Quinn, D.A., and Ghofrani, H.-A.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Circulation
ISSN (Online):1524-4539
Published Online:12 February 2013

University Staff: Request a correction | Enlighten Editors: Update this record