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Education Posts

Group PAH

Article Type: Treatments

Pharmacotherapy in Pulmonary Arterial Hypertension: A Systemic Review and Meta-Analysis

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

Citation
Ryerson CJ, Nayar S, Swiston JR, Sin DD. Pharmacotherapy in pulmonary arterial hypertension: a systematic review and meta-analysis. Respir Res. 2010 Jan 29;11(1):12.
Source: https://pubmed.ncbi.nlm.nih.gov/20113497/

Imnatinib Mesylate as add-on Therapy for Pulmonary Arterial Hypertension: Results of the Randomized Impres Study

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.

Citation
Hoeper MM, Barst RJ, Bourge RC, Feldman J, Frost AE, Galié N, Gómez-Sánchez MA, Grimminger F, Grünig E, Hassoun PM, Morrell NW, Peacock AJ, Satoh T, Simonneau G, Tapson VF, Torres F, Lawrence D, Quinn DA, Ghofrani HA. Imatinib mesylate as add-on therapy for pulmonary arterial hypertension: results of the randomized IMPRES study. Circulation. 2013 Mar 12;127(10):1128-38.
Source: https://pubmed.ncbi.nlm.nih.gov/23403476/

Imatinib in Pulmonary Arterial Hypertension Patients with Inadequate Response to Established Therapy

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.

Citation
Ghofrani HA, Morrell NW, Hoeper MM, Olschewski H, Peacock AJ, Barst RJ, Shapiro S, Golpon H, Toshner M, Grimminger F, Pascoe S. Imatinib in pulmonary arterial hypertension patients with inadequate response to established therapy. Am J Respir Crit Care Med. 2010 Nov 1;182(9):1171-7.
Source: https://pubmed.ncbi.nlm.nih.gov/20581169/

Reversal of Experimental Pulmonary Hypertension by PDGF Inhibition

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.

Citation
Schermuly RT, Dony E, Ghofrani HA, Pullamsetti S, Savai R, Roth M, Sydykov A, Lai YJ, Weissmann N, Seeger W, Grimminger F. Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest. 2005 Oct;115(10):2811-21.
Source: https://pubmed.ncbi.nlm.nih.gov/16200212/
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