Systematic review and meta-analysis of interventions tested in animal models of pulmonary hypertension.

A systematic review and meta-analysis was performed to test candidate therapeutic approaches in pulmonary hypertension (PH). The efficacy of 522 interventions with >200 unregistered drugs was tested on 7254 animals. We propose a modified formula to assess meta-data that concerns the contribution of PH animal model to the denoted efficacy of tested agents. The measure of efficacy expressed as a response ratio for right ventricle systolic pressure was 0.48 (95% CI, 0.46-0.50; P < 0.00001), mean pulmonary artery pressure was 0.54 (0.52-0.56; P < 0.00001), right ventricle hypertrophy was 0.49 (0.48-0.51; P < 0.00001) and pulmonary artery wall thickness was 0.58 (0.56-0.61; P < 0.00001). Only 41 out of 522 interventions were ineffective. The most potent agents to improve both haemodynamic and hypertrophic parameters were ATP-sensitive potassium channel openers with iptakalim, Rho/ROCK inhibitors with fasudil, RAAS regulators with adenosine and ACE2 activators, and anti-inflammatories with n-3 polyunsaturated fatty acids and NF-кB inhibitors.