Effects of pulmonary arterial hypertension therapies on arterial oxygenation in patients with pulmonary hypertension associated with lung disease: a systematic review and meta-analysis

BACKGROUND: Pulmonary hypertension (PH) associated with lung disease entails a poor prognosis. There is concern about the potential deleterious effect on gas exchange of drugs approved for pulmonary arterial hypertension (PAH) in patients with lung disease. We conducted a systematic review on the effects of drugs approved for PAH on arterial oxygenation in randomised clinical trials (RCTs) conducted in patients with PH associated with lung disease. METHODS: Five databases were searched until May 2025. We included RCTs with PAH therapies in patients with PH associated with lung disease that reported measurements of arterial oxygenation, either the partial pressure of arterial oxygen (PaO2) or the arterial oxygen saturation (SpO2). For analysis purposes, both measurements were merged into one single variable called 'overall oxygenation'. As secondary outcomes, we analysed the use of supplemental oxygen and the presence of adverse events related to oxygenation. RESULTS: Of the 393 reports returned by the initial search, nine articles, reporting 827 patients (64.6% male), were included. The overall oxygenation at the end of the trial in the intervention group (IG), treated with a PAH therapy, was similar to the control group (standard mean difference (SMD) -0.00; 95% CI -0.17 to 0.18; p=0.98). Similarly, the change in overall oxygenation postintervention in the IG was similar to the control group (SMD 0.01; 95% CI -0.22 to 0.24; p=0.91). Reported adverse events related to oxygenation were similar in the treatment and control arms. CONCLUSION: There is currently no consistent evidence from RCTs to suggest a deleterious effect of PAH therapies on arterial oxygenation in patients with PH associated with lung disease. PROSPERO REGISTRATION NUMBER: CRD42022349299.