The effect of ras human orthologue kinase inhibitor on the treatment of pulmonary hypertension: a systematic review
Authors: Alamsyah A H , Alamsyah A Z , Hermawan I K H 
Published: January 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Pulmonary hypertension (PH) is a high mortality and an uncrackable disease up to date. The complex pathophysiology is one of the reasons for only a view treatment that can be given to patients with PH. Recent studies have found that ras human orthologue–kinase (Rho-kinase) plays a role in the pathophysiology of pulmonary hypertension. Rho-kinase maintains vasoconstriction and increases vasoreactivity in vascular smooth muscle. Although the theory outlining the impact of rho-kinase on the pathophysiology of PH is well established, studies on the use of rho-kinase inhibitors as a treatment for this population are few.

Purpose
This study aims to evaluate the effect of rho-kinase inhibitors in the treatment of pulmonary hypertension patients.

Methods
A systematic review based on PRISMA guidelines was conducted. We searched PubMed, ScienceDirect, ProQuest, Cochrane Library, and Scopus Library for studies evaluating the effect of Rho-kinase inhibitor in pulmonary hypertension patients. All English articles that related to this topic were included with no time limit. The outcome of interest is pulmonary hemodynamic parameters changes pre-and post-treatment with only parameters included if described in two or more studies. We assessed the quality of the study using the Newcastle Ottawa scale for observational study and the Cochrane risk of bias tools for randomized control trials study.

Results
Seven studies met the criteria including 254 Patients. The mean age was 40.1 years old and 36.8% were male. All the studies included PH patients but differ in the type of PH. Fasudil 30 mg or 60 mg was the regimen of the Rho-kinase inhibitor that was used. Several pulmonary hemodynamic parameters were included in this review: pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), mean pulmonary arterial pressure (mPAP), mean systemic arterial pressure (mSAP), cardiac index (CI), right arterial pressure (RAP), systolic pulmonary arterial pressure (sPAP), diastolic pulmonary arterial pressure (dPAP), pulmonary capillary wedge pressure (PCWP) and pulmonary/systemic blood flow ratio (Qp/Qs ratio). All studies that described PVR, sPAP, dPAP, and Qp/Qs ratio found that rho-kinase inhibitors significantly improve those parameters. Significant improvement of mPAP was found in 4 studies but one found it not significant.CI and SVR showed to be significantly improved in 3 studies, but 2 showed no significance. Overall, our findings suggest that Rho-kinase inhibitor can successfully improve several pulmonary hemodynamic parameters in pulmonary hypertension patients.

Conclusion
Rho-kinase plays a role in the pathophysiology of pulmonary hypertension and the use of Rho-kinase inhibitors has been shown to improve several pulmonary hemodynamic parameters in pulmonary hypertension patients. Future studies conducted clinical trials and meta-analysis is needed to confirm the findings of this study.