The role of imatinib in the treatment of pulmonary hypertension.

Imatinib mesylate, a receptor tyrosine kinase inhibitor that has been approved for several oncology conditions, is currently under investigation for pulmonary arterial hypertension. The therapeutic rationale is that its targets, platelet-derived growth factor receptor beta (PDGFR-β) and proto-oncogene c-Kit, are pivotal for the proliferation, migration and apoptosis resistance of peripheral artery smooth muscle cells which reduces the lumen of the pulmonary artery, leading to diminished blood oxygenation and pressure overload in the right heart ventricle. Interfering with this process could slow disease progression, which is incompletely addressed by current therapies which focus on vasorelaxation. Results from two efficacy studies have been reported; while the first missed its primary endpoint (but provided valuable insights on efficacy in subgroups), the phase III IMPRES study and its ongoing extension revealed an impressive degree of added benefit for imatinib against a background of conventional combination therapy. The side effect profile of imatinib in this condition requires more investigation.