AUTHOR=Liu Yu-Yang , Qu Yi-Yang , Wang Shang , Luo Ci-Jun , Qiu Hong-Ling , Li Hui-Ting , Yuan Ping , Wang Lan , Li Jin-Ling , Jiang Rong , Zhang Rui 

TITLE=Efficacy and safety of riociguat replacing PDE-5is for patients with pulmonary arterial hypertension: A systematic review and meta-analysis

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1052546

DOI=10.3389/fphar.2023.1052546

ISSN=1663-9812

ABSTRACT=<p><bold>Introduction:</bold> Pulmonary arterial hypertension (PAH) is a rare and progressive disease. Some patients treated with phosphodiesterase type 5 inhibitors (PDE-5is) fail to reach treatment goals. As a novel soluble guanylate cyclase agonist, riociguat acts on the same pathway as PDE-5is but functions <italic>via</italic> different mechanisms. Whether riociguat is more effective and safer than PDE-5is is ambiguous. We aimed to evaluate the efficacy and safety of switching from PDE-5is to riociguat among these patients.</p><p><bold>Methods:</bold> Original published articles were retrieved from PubMed/Medline, Embase, Web of Science, Open Grey and Google Scholar. Studies that assessed the World Health Organization functional class (WHO-FC), 6-min walking distance (6MWD), pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), cardiac index (CI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were collected. Adverse events after switching were evaluated.</p><p><bold>Results:</bold> Ten published studies were included. Compared to PDE-5is, riociguat significantly increased the 6MWD by 26.45 m weighted mean difference (WMD) = 26.45 m, 95% confidence intervals (CIs): 9.70–43.2 m, <italic>p</italic> = 0.002) and improved mPAP (WMD = −3.53, 95% CIs: −5.62–1.44 mmHg, <italic>p</italic> = 0.0009), PVR (WMD = −130.24 dyn·s·cm<sup>−5</sup>, 95% CI −187.43–73.05, <italic>p &lt;</italic> 0.0001), CIs (WMD = 0.36 L/min·cm<sup>−2</sup>, 95% CIs: 0.25–0.47, <italic>p &lt;</italic> 0.00001) and WHO-FC (OR = 0.11, 95% CIs: 0.08–0.16, <italic>p</italic> &lt; 0.0001) but not NT-proBNP. In addition, we did not observe the most common side effects during the replacement of riociguat for PDE-5is.</p><p><bold>Conclusions:</bold> Compared to PDE5i, PAH patients benefit more from riociguat in hemodynamics, 6MWD, WHO-FC and biomarkers.</p>