Balloon Pulmonary Angioplasty Versus Riociguat in Inoperable Chronic Thromboembolic Pulmonary Hypertension: Systematic Review and Meta-Analysis of Randomized Controlled Trials

Chronic thromboembolic pulmonary hypertension (CTEPH) results from unresolved pulmonary emboli that lead to persistent obstruction of the pulmonary vasculature, elevated pulmonary arterial pressure, and subsequent right-heart strain. About half of CTEPH patients cannot have surgery to remove blockages and need other treatments—either balloon pulmonary angioplasty (BPA), a procedure that widens vessels, or riociguat, a medication that relaxes them. We followed PRISMA guidelines and searched PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov for randomized trials from January 2018 to April 2025 that directly compared BPA and riociguat in adults with inoperable CTEPH. We pooled data from 3 trials (262 patients total: 134 BPA, 128 riociguat) using random-effects models and checked consistency with I² and leave-one-out tests. Compared to riociguat, BPA reduced mean pulmonary arterial pressure by 12.23 mm Hg (95% CI, 15.32–9.15; I² = 82%), pulmonary vascular resistance by 208.58 dyn·s/cm⁵ (95% CI, 299.85–117.32; I² = 87%), right atrial pressure by 2.18 mm Hg (95% CI, 3.13–1.23; I² = 66%), and NT-proBNP by 989.61 pg/mL (95% CI, 1456.66–522.55; I² = 0%) (all P < 0.0001). Riociguat led to a larger increase in cardiac output (0.47 L/min; 95% CI, 0.37–0.58; I² = 0%; P < 0.00001). Removing the Kawakami trial eliminated heterogeneity (I² = 0%). Both treatments were similarly safe. In summary, BPA delivers stronger pressure and biomarker improvements, while riociguat better boosts heart output. Combining or sequencing these treatments deserves further study in larger trials.