Pulmonary Vasodilators in COPD-Associated Pulmonary Hypertension: An Updated Meta-Analysis of Randomized Evidence

Background: Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD), termed COPD-associated pulmonary hypertension (COPD-PH), and is associated with worse clinical outcomes. The efficacy and safety of pulmonary vasodilators in COPD-PH remain uncertain. Methods: We performed a systematic review and meta-analysis of randomized studies evaluating pulmonary vasodilators in adults with COPD-PH. Fifteen studies were identified, with 11 contributing to quantitative analyses. Outcomes included six-minute walk distance (6MWD), mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), partial pressure of arterial oxygen (PaO2), and systolic pulmonary arterial pressure (sPAP). Results: Pulmonary vasodilators significantly reduced mPAP (MD −3.88 mmHg, 95% CI −7.23 to −0.53) and PVR (SMD −0.90, 95% CI −1.70 to −0.10). However, no significant improvements were observed in 6MWD or PaO2. An exploratory composite hemodynamic score supported an overall hemodynamic benefit. Subgroup analyses suggested a more favorable profile for nitric oxide donors, whereas endothelin receptor antagonists were associated with worsened oxygenation. Conclusions: Pulmonary vasodilators improve pulmonary hemodynamics in COPD-PH but do not consistently improve exercise capacity or oxygenation. Current evidence does not support routine use outside specialized centers or clinical trials, and treatment effects appear to vary by drug class.