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Riociguat for the Treatment of Pulmonary Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Linlin Dang, Yurong Zhang, Xiaoli Mou, Tingting Shu, Min Cao, Ai-Ai Chu

Background: The treatment of Pulmonary Arterial Hypertension (PAH) and Chronic Thromboembolic Pulmonary Arterial Hypertension (CTEPH) with riociguat is approved and can significantly improve patients' exercise tolerance, hemodynamic parameters, cardiac function, etc. However, for pulmonary arterial hypertension caused by other reasons, the therapeutic effect of riociguat needs further verification. The purpose of this article is to evaluate the therapeutic effect of riociguat on patients with pulmonary arterial hypertension.

Method: A computer was used to conduct literature search on commonly used databases, including EMbase, PubMed, Web of Science, and Cochrane Library, to collect clinical studies related to riociguat and pulmonary arterial hypertension. The search was conducted from database establishment to November 16, 2023 using RevMan 5.4 software for meta-analysis.

Result: Our study included 12 randomized controlled trials. For PAH and CTEPH patients, after receiving riociguat treatment, the 6-Minute Walking Distance (6MWD) was extended by 37.49 meters, with an average reduction of 4.19 mmHg in Pulmonary Arterial Pressure (PAP), 213.53 dynes/second/cm^-5 in Pulmonary Vascular Resistance (PVR), 0.75 mmHg in Right Atrial Pressure (RAP), 0.47 l/min/m² in Cardiac Index (CI), 0.85 l/min in Cardiac Output (CO), 455.31 pg/ml in N-terminal pro-type B Natriuretic Peptide (NT-proBNP), and a reduction in adverse events and clinical deterioration compared to placebo. For other types of Pulmonary Hypertension (PH), including those caused by left heart disease and those caused by lung disease, it has been reported that riociguat extended the 6MWD by 34.9 meters, increased CI by 0.35 l/min, increased CO by 0.67 l/min, and decreased PVR by 41.12 dynes/second/cm-5 compared to placebo. There was no statistically significant difference in other efficacy and safety outcomes among other types of Pulmonary Hypertension (PH).

Conclusion: Our meta-analysis showed that riociguat effectively improved exercise ability and cardiopulmonary hemodynamics in patients with PAH and CTEPH, and was relatively safe and well tolerated for patients with other types of pulmonary hypertension, riociguat treatment may improve their exercise ability, and indicators such as CI, CO, and PVR in cardiopulmonary hemodynamics may also be improved.