Abstract
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, I(2) = 93%) improved 6MWD better than ERAs (MD = 41.60, 95% CI: 21.76-61.44, P < 0.0001, I(2) = 32%) and PDE5i (MD = 52.33, 95% CI: 29.16-75.50, P < 0.0001, I(2) = 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.