Riociguat 1mg tablets

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encompassed case reports, systematic reviews, review articles, conference abstracts with no full text (since they were not peer-reviewed), non-full-text articles, non-English manuscripts, opinion articles, and book chapters.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.

Abstract licence: CC BY

BackgroundPulmonary hypertension (PH) is a progressive, life-threatening condition characterized by elevated pulmonary arterial pressure, often culminating in right heart failure. Despite existing therapies, optimizing treatment efficacy and safety remains a clinical challenge. Riociguat, a soluble guanylate cyclase stimulator, has shown promise in managing PH, particularly in pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). This meta-analysis aims to evaluate the optimal dosing of riociguat to maximize therapeutic benefits while minimizing adverse effects.MethodsThis systematic review and meta-analysis followed PRISMA guidelines. A comprehensive search of PubMed, Cochrane Central, Embase, and Google Scholar was conducted to identify randomized controlled trials (RCTs) comparing riociguat with placebo in adult PH patients. Eligible studies included double-arm RCTs with riociguat dosages ranging from 0.5 to 2.5 mg. Primary outcomes included changes in 6-minute walk distance (6-MWD), mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), and NT-proBNP levels. Secondary outcomes were adverse events and clinical worsening. Study quality was assessed using the Cochrane risk of bias tool. Statistical analysis used RevMan 5.4 with a random-effects model. Heterogeneity was evaluated using χ2 and I2 tests, and meta-regression assessed the impact of age and BMI.ResultsTen RCTs involving 1109 PH patients were included. Riociguat significantly improved 6-MWD (MD: 27.23 m; 95% CI: 8.28-46.18; P = .005), reduced mPAP (MD: -2.61 mm Hg; 95% CI: -4.60 to -0.63; P = .01), lowered PVR (MD: -90.27 dynes·s·cm-5; 95% CI: -119.30 to -61.23; P ConclusionsRiociguat demonstrates dose-dependent efficacy in improving functional and hemodynamic parameters in PH, with the 2.5 mg thrice-daily dose showing consistent benefit. BMI impacted functional outcomes but not hemodynamic measures. These findings support tailored dosing strategies for optimized patient outcomes. Further research is needed to confirm dose-response effects and address residual heterogeneity.

Abstract licence: CC BY