Imatinib Mesylate as Add-On Therapy for Pulmonary Arterial Hypertension: Results of the Randomized IMPRES Study
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—IMPRES, a randomized, double-blind, placebo-controlled 24-week trial evaluated imatinib in patients with pulmonary vascular resistance (PVR) ≥800 dynes•sec•cm-5 symptomatic on ≥2 PAH therapies. The primary outcome was change in 6-minute walk distance (6MWD). Secondary outcomes included changes in hemodynamics, functional class, serum levels of N-terminal brain natriuretic peptide (NT-proBNP), and time to clinical worsening (TTCW). 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 6MWD was 32 m (95% confidence interval [CI], 12, 52; P=0.002), an effect maintained in the extension study in patients remaining on imatinib. PVR decreased by 379 dynes•sec•cm-5 (95% CI: -502, -255; P<0.001; between-group difference). Functional class, TTCW and mortality did not differ between treatments. Serious adverse events and discontinuations were more frequent with imatinib than placebo (44% versus 30%, 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.
- Received December 21, 2012.
- Revision received January 11, 2013.
- Accepted January 14, 2013.
- Copyright © 2013, Circulation