Objective: The aim of this study was to systematically evaluate the effect of pulmonary arterial hypertension (PAH) targeting drugs on exercise tolerance in Eisenmenger syndrome (ES) and analyze related factors.

Methods: Two researchers conducted an independent search of the Chinese database and the English database, and conducted literature screening, data extraction and quality evaluation according to the inclusion and exclusion criteria respectively. According to the heterogeneity test results, the effect model was adopted for analysis by RevMan5.4 statistical software, in which the continuity data were represented by mean difference (MD) and 95% confidence interval (CI).

Results: A total of 393 patients with ES were included in 13 papers, including 8 studies of endothelin receptor antagonists (ERA), 2 studies of phosphodiesterase 5 inhibitors (PDE5i) and 3 studies of prostanoids. The results of these studies showed that the targeted drugs were effective in improving exercise tolerance in ES patients. Further analyses revealed that the differences in efficacy were related to the type of targeted drug, duration of drug treatment and the presence or absence of Down syndrome (DS). 6MWD (6 min Walk Distance) and cardiac function were significantly improved in ES patients with all three classes of drugs. Prostanoids (MD = 132.35, 95% CI: 14.82-249.89, P < 0.0001, I² = 93%) improved 6MWD better than ERAs (MD = 41.60, 95% CI: 21.76-61.44, P < 0.0001, I² = 32%) and PDE5i (MD = 52.33, 95% CI: 29.16-75.50, P < 0.0001, I² = 0). Prostanoids demonstrated a more significant improvement in cardiac function compared to ERAs and PDE5i. Specifically, prostanoids [MD= -1.26, 95% CI: (-1.66, -0.86), P < 0.0001] showed a greater improvement than ERAs [MD=-0.54, 95% CI: (-0.96, -0.11), P = 0.01] and PDE5i [MD=-0.38, 95% CI: (-0.64, -0.13), P = 0.003]. Short-term pharmacological therapy (less than 12 months) significantly increased 6MWD and improved clinical cardiac function in included patients. Continued targeted drug therapy further increased the level of cardiac function (P < 0.0001). Targeted drug therapy was effective in increasing 6MWD in patients with ES combined with DS, but had no significant effect on cardiac function class. Targeted drug therapy had a favorable effect on both 6MWD and cardiac function class in non-DS patients.

Conclusion: Early targeted drug therapy for ES can significantly improve the exercise tolerance of patients, and a better drug regimen and treatment time should be selected according to the clinical characteristics of patients.

Keywords: Correlation factor; Eisenmenger syndrome; Exercise tolerance; Pulmonary hypertension targeting drugs.

© 2025. The Author(s).

目标： 本研究旨在系统评价肺动脉高压（PAH）靶向药物对艾森曼纳综合征（ES）患者运动耐量的影响，并分析相关因素。

方法： 两位研究人员分别独立检索中文数据库和英文数据库，根据纳入与排除标准进行文献筛选、数据提取和质量评价。根据异质性检验结果，采用RevMan5.4统计软件对效果模型进行分析，其中连续数据用均差（MD）及其95%置信区间表示。

结果： 共纳入13篇文献的393例ES患者，包括8项内皮素受体拮抗剂（ERA）、2项磷酸二酯酶5抑制剂（PDE5i）和3项前列环素的研究。结果显示，靶向药物对改善ES患者的运动耐量有效。进一步分析发现，疗效差异与所使用的靶向药物类型、用药持续时间以及是否存在唐氏综合征（DS）有关。三类药物均显著提高了ES患者的6分钟步行距离（6MWD）和心脏功能。前列环素（MD = 132.35, 95% CI: 14.82-249.89, P

结论： 早期针对ES患者的靶向药物治疗可显著改善其运动耐量，应根据患者的临床特征选择更优的用药方案和治疗时间。

© 2025. The Author(s).