HMG-COA reductase inhibitors: An opportunity for the improvement of imatinib safety. An experimental study in rat pulmonary hypertension.

Background: Co-administration of statin with imatinib is thought to result in greater improvement in pulmonary arterial hypertension (PAH) than imatinib treatment alone, and hence may allow greater effectiveness of imatinib therapy at lower doses.

Methods: The effects of imanitib at dose of 20 and 50mg/kg bw given together with rosuvastatin or simvastatin were investigated with respect to right ventricle pressure (RVP), arterial blood pressure and right ventricle hypertrophy (RVH) in experimental monocrotaline (MCT)-induced pulmonary hypertension. Fourteen days after MCT injection, male rats were treated orally for another 14 days with imatinib, statin or a combination of the two.

Results: Concurrent administration of statin (lipophilic simvastatin, hydrophilic rosuvastatin) and higher dose imatinib reversed the MCT-induced increase in RVP more than each drug alone and decreased RV hypertrophy (RV/LV+S ratio), significantly. The increased RVP and RV hypertrophy was found to be reversed when a lower dose of imatinib was co-administered with rosuvastatin or simvastatin.

Conclusions: Statins may intensify the beneficial effects of imatinib in PAH, which may be due to the additional influence of statin on the decrease of platelet-derived growth factor (PDGF)-induced effects. These properties allow the dose of imatinib used in PAH treatment to be reduced and thereby might improve its safety profile.