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 mmHg to 45.6 ± 15.4 mmHg (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 mmHg vs. 10.5 ± 4.0 mmHg, P = 0.53). The 6-minute 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 mmHg to 83.5 ± 13.9 mmHg 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 mmHg vs. 3.5 ± 2.7 mmHg, 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.