ReviewPulmonary circulation2026
The Therapeutic Efficacy of Drugs Targeting the NO-sGC-cGMP Pathway in Treatment of Patients With Chronic Thromboembolic Pulmonary Hypertension: A Systematic Review.
Review in Pulmonary circulation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Authors and funding
10 authors.
Funding
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Abstract
Chronic thromboembolic pulmonary hypertension (CTEPH) is a distinct and potentially curable form of pulmonary hypertension; however, a substantial proportion of patients remain inoperable or experience persistent or recurrent disease. Pharmacological therapies targeting the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) pathway have emerged as promising treatment options. Therefore, this systematic review aimed to comprehensively evaluate the therapeutic efficacy of drugs targeting the NO-sGC-cGMP pathway on clinical outcomes in patients with CTEPH. We conducted a comprehensive search of electronic databases, including Embase, MEDLINE, Cochrane Library, and Scopus databases from inception to December 1, 2025. Studies involving adult patients with confirmed CTEPH receiving NO-sGC-cGMP pathway-targeted therapies were included. Exclusion criteria encompassed case reports, systematic reviews, review articles, conference abstracts with no full text (since they were not peer-reviewed), non-full-text articles, non-English manuscripts, opinion articles, and book chapters. Risk of bias was assessed using the Cochrane RoB 2 tool and the Newcastle-Ottawa Scale. A total of 23 studies involving 2815 patients were included. The most frequently investigated agents were riociguat and sildenafil. Fourteen of 15 studies demonstrated significant improvements in exercise capacity, with consistent findings reported in major trials such as CHEST-1 and its long-term extension, CHEST-2. All 16 studies assessing pulmonary hemodynamics reported significant improvements in mPAP, PVR, and CO. Additionally, 12 studies showed reductions in NT-proBNP levels and improvements in WHO-FC, indicating enhanced functional status. Quality of life was assessed in two studies, both of which demonstrated favorable outcomes. Furthermore, three studies reported improvements in right ventricular function and risk stratification. Pharmacological agents targeting the NO-sGC-cGMP pathway, particularly riociguat and sildenafil, demonstrate consistent improvements in exercise capacity, pulmonary hemodynamics, functional status, and biomarkers in patients with CTEPH. These findings support their role as effective therapeutic options, especially in inoperable or persistent CTEPH. Nevertheless, further large-scale, high-quality randomized controlled trials are warranted to strengthen the evidence base and optimize treatment strategies. Systematic review registration: CRD42024510274, https://www.crd.york.ac.uk/PROSPERO/view/CRD42024510274.
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