Qiang Li ¹ Hongyu Kuang ² Huaan Du ^3*

• ¹ Children‘s Hospital of Chongqing Medical University, Chongqing, Chongqing Municipality, China
• ² Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
• ³ University-Town Hospital of Chongqing Medical University, Chongqing, China

Purpose: To systematically evaluate the clinical efficacy and safety of targeted drugs in patients with pulmonary arterial hypertension (PAH) with cardiac function grades III to IV, and conduct a meta-analysis. Methods: Two researchers independently searched the PubMed, EMBASE, and Cochrane Library databases for relevant studies, with the search period extending from the establishment of the databases to March 2024. For continuous variables, the 6-minute walk distance (6MWD) was expressed as the mean difference (MD), while hemodynamic parameters were represented by the standard mean difference (SMD). For categorical variables, the odds ratio (OR) was used. The confidence interval (CI) was set at 95%, and a p-value of less than 0.05 was considered statistically significant. Results: Ten randomized controlled trials (RCTs) involving 553 patients with PAH and cardiac function grades III-IV were ultimately included. Three RCTs targeted the endothelin pathway, five targeted the prostacyclin pathway, and two assessed the effects of combination therapy. Meta-analysis and subgroup analysis revealed that short-term monotherapy with bosentan significantly improved 6MWD by approximately 53.67 meters (95% CI: [43.57, 63.77] meters, p<0.0001) in patients with FC III-IV PAH. Additionally, prostacyclin analogs increased 6MWD by approximately 25.02 meters (95% CI: [19.22, 30.81] meters, p<0.0001) in this patient population. Further hemodynamic assessments demonstrated that both bosentan monotherapy and prostacyclin analog therapy significantly reduced pulmonary vascular resistance, with SMDs of -1.07 (95% CI [-2.08, -0.06], p=0.04) and -1.26 (95% CI=[-2.21, -0.32], p=0.009), respectively. Analysis of the clinical efficacy of combination therapy in PAH patients revealed that while it did not significantly improve 6MWD, cardiac function improved in approximately 59.1% of patients (95% CI=[38.5%, 79.6%]). Safety analysis indicated that combination targeted therapy did not significantly increase the incidence of severe adverse events in PAH patients. Conclusion: Monotherapy with targeted drugs is safe and effective for patients with PAH and cardiac function grades III-IV. Combination therapy can significantly improve cardiac dysfunction in these patients without significantly increasing the risk of severe adverse events.