Unbiased meta-analysis of the approved pulmonary vasodilator therapies for PAH. The authors improved upon two previous meta-analyses by addressing some of the limitations in those analyses. By pooling the available literature, they sought to determine the effect of the classes of medication on total mortality and secondarily to assess their impact on other clinical endpoints, including dyspnea, exercise tolerance, hemodynamics, and adverse effects
Report of the Phase 3 trial of imatinib for PAH. This study confirms the potential efficacy of imatinib as a treatment, the first disease modifying approach for PAH. Unfortunately, the excess of dropouts in the imatinib group attributed to side effects prevented regulatory approval.
This is the phase 2 randomized clinical trial of imatinib for PAH to test its efficacy and safety. There were non-significant increases in 6-minute walk, with significant reductions in pulmonary vascular resistance. The relatively small number of patients (59) makes interpretation of the results difficult. It appeared that the patients with more advanced disease responded better than those with lesser disease. This trial was used to justify pursuing a phase 3 trial for regulatory approval.
This classic paper describes the experimental data from testing imatinib in animal models of pulmonary hypertension which justified Novartis to pursue its potential in PAH. The inclusion of data from human lungs of patients with PAH showing elevation of the expression of PDGF receptors make a compelling argument for the testing of imatinib in clinical trials.