Comparison of Dual- versus Triple-Targeted Drug Therapy for Patients with Left-To-Right Shunt Congenital Heart Disease-Associated Pulmonary Arterial Hypertension

INTRODUCTION: Evidence on dual- and triple-targeted therapy in patients with left-to-right shunt congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH) remains limited. We compared the efficacy of triple- versus dual-targeted drug therapy in patients with CHD-PAH and evaluated treatment outcomes and prognosis. METHODS: In all, 67 patients with CHD-PAH received targeted drug therapy and were evaluated for potential defect closure. Patients were categorized into closure and non-closure groups and further subdivided into dual- or triple-targeted therapy groups. Follow-up assessments, including echocardiography, were conducted every 3-6 months over 12-35 months (mean: 2 years). RESULTS: The mean patient age was 42.4 ± 17.7 years. Twenty-five patients (37.3%) successfully underwent CHD closure. At the last follow-up, the mean pulmonary artery systolic pressure (PASP) significantly decreased from 78.8 ± 21.3 mm Hg to 45.6 ± 15.4 mm Hg (p < 0.001). At the 3-month follow-up, the reduction in PASP did not differ significantly between the triple- and dual-targeted therapy groups (13.8 ± 13.0 mm Hg vs. 10.5 ± 4.0 mm Hg, p = 0.53). The 6-min walk distance (6MWD) improved from 183.6 ± 29.7 m to 251.4 ± 89.9 m (p < 0.001). In the non-closure group, PASP decreased from 92.9 ± 29.0 mm Hg to 83.5 ± 13.9 mm Hg at the last follow-up (p = 0.005). At the 3-month follow-up, PASP reduction was significantly greater in the triple-targeted therapy group than that in the dual-targeted therapy group (9.2 ± 7.4 mm Hg vs. 3.5 ± 2.7 mm Hg, p = 0.004). The 6MWD also improved, from 164.9 ± 29.3 m to 202.7 ± 32.2 m, though the difference was not statistically significant (p = 0.64). CONCLUSION: Combination targeted therapy is effective for patients with left-to-right shunt CHD-PAH, regardless of closure status. Among patients not eligible for closure, triple-targeted therapy demonstrated superior efficacy compared to dual-targeted therapy.