A Systematic Review of Novel Therapies of Pulmonary Arterial Hypertension

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Abstract Pulmonary arterial hypertension (PAH) is a progressive cureless disease, characterized by increased pulmonary vascular resistance and remodeling, with subsequent ventricular dilatation and failure. New therapeutic targets are being investigated for their potential roles in improving PAH patients’ symptoms and reversing pulmonary vascular pathology. We aimed to address the available knowledge from the published randomized control trials (RCTs) concerning the role of Rho kinase (ROCK) inhibitors, Bone morphogenetic protein 2 (BMP2) inhibitors, Estrogen inhibitors, and AMP- activated protein kinases (AMPK) activators on the PAH evaluation parameters. This systematic review (SR) was registered on PROSPERO (CDR42022340658) and followed the PRISMA guidelines. About 5092 records were screened from different database and registries and only 8 RCTs that met our inclusion criteria were included. The marked difference in the study designs and the variability of the selected outcome measurement tools among the studies made performing a meta-analysis impossible. Yet, the main findings of this SR are the powerful potential of the AMPK activator and the imminent anti-diabetic drug, metformin and the BMP2 inhibitor, sotatercept as promising PAH modifying therapies. There is a need for long-term studies to evaluate the effect of the ROCK inhibitor, fasudil and the estrogen aromatase inhibitor, anastrozole in PAH patients. Tacrolimus role in PAH is query. The discrepancy in the hemodynamic and clinical parameters necessitates defining cut values to predict improvement. The differences in the PAH etiologies render the judgment of the therapeutic potential of the tested drugs challenging.

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