Abstract
BACKGROUND: Pulmonary arterial hypertension (PAH) is a serious complication of chronic obstructive pulmonary disease (COPD) that markedly worsens functional capacity and prognosis. Fasudil, a selective Rho-kinase inhibitor, has shown vasodilatory and vascular-protective effects; however, its therapeutic value in COPD-associated PAH has not been systematically quantified. OBJECTIVE: The objective of the study was to evaluate the efficacy of fasudil as an adjunctive therapy for COPD patients with PAH through a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: Eight electronic databases were searched from inception to April 2024 for RCTs comparing fasudil plus conventional therapy with conventional therapy alone. Primary outcomes included overall treatment effectiveness and pulmonary artery systolic pressure (PASP). Secondary outcomes were blood oxygen saturation (SaO₂), arterial oxygen tension (PaO₂), and 6-min walk distance (6MWT). Data were pooled using fixed- or random-effects models according to heterogeneity. RESULTS: A total of 11 RCTs involving 865 participants met the inclusion criteria. Fasudil significantly increased the overall effective rate (risk ratio = 1.18, 95% CI = 1.05-1.31, p = 0.004) and reduced PASP (mean difference = -9.42 mmHg, 95% CI = -10.73 to -8.12, p < 0.001) with negligible heterogeneity. Chronic treatment (≥2 weeks) improved SaO₂ (MD = 3.56, 95% CI 1.73-5.40), whereas single-dose administration had a minimal effect. PaO₂ increased modestly (MD = 2.19 mmHg, 95% CI = 0.84-3.54, p = 0.002). Functional capacity improved substantially, with a 51.96-m gain in 6MWT distance (95% CI = 36.84-67.08, p < 0.001), exceeding the minimal clinically important difference. CONCLUSION: Fasudil confers consistent short-term benefits in COPD-related PAH, significantly lowering pulmonary pressures and enhancing oxygenation and exercise tolerance. While the included studies were of moderate methodological quality and limited to Chinese settings, the pooled evidence supports fasudil as a promising adjunct for managing COPD-associated PAH. Larger, multicenter RCTs with longer follow-up are warranted to confirm its long-term efficacy and safety. The short follow-up (maximum 4 weeks) limits insights into sustained benefits or progression; long-term trials are essential.