Abstract
BACKGROUND: The prognosis and long-term survival of high-risk coronary syndrome patients with pulmonary hypertension (PH) remain unsatisfactory, and limited research has evaluated the synergistic therapeutic effects of endothelin receptor antagonists (ERAs) combined with soluble guanylate cyclase agonists (sGCAs). This study aimed to assess the synergistic cardiopulmonary protective effects and clinical safety of ERA combined with sGCA therapy in patients with high-risk coronary syndrome complicated by PH. METHODS: This retrospective controlled study included 132 patients with high-risk coronary syndrome and PH who were admitted between January 2019 and December 2023. After exclusion criteria were applied, 119 patients were analyzed and categorized into a control group (ambrisentan monotherapy, n = 58) and an experimental group (ambrisentan plus riociguat, n = 61) according to the associated treatment strategy. Primary endpoints included 6-minute walk distance (6MWD), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and the World Health Organization-related functional class (WHO-FC). Secondary endpoints included cardiac index (CI), left ventricular end-diastolic diameter (LVEDD), tricuspid annular plane systolic excursion (TAPSE), mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), Borg dyspnea score (BDS), and the incidence of adverse events. RESULTS: Baseline characteristics between the two groups were comparable (all p > 0.05). Following treatment, the 6MWD, CI, and TAPSE values significantly improved in both groups (all p < 0.05), with greater improvements observed in the experimental group (95% CI: -3.61 to -0.05, p = 0.044; 95% CI: -0.20 to -0.004, p = 0.039; 95% CI: -0.29 to -0.07, p = 0.001). The NT-proBNP, LVEDD, mPAP, PVR, and BDS values decreased in both cohorts (all p < 0.05), with more pronounced reductions in the experimental group (95% CI: 0.02-3.5, p = 0.048; 95% CI: 0.03-0.21, p = 0.012; 95% CI: 0.02-2.03, p = 0.046; 95% CI: 0.65-4.30, p = 0.008; 95% CI: 0.06-0.78, p = 0.022). The proportion of individuals in the WHO-FC classes III-IV was lower in the experimental group (95% CI: 1.05-4.56, p = 0.035). No statistically significant difference in adverse-event incidence was observed between groups (95% CI: 0.73-5.03, p = 0.184). CONCLUSION: Combination therapy with ambrisentan and riociguat effectively improved cardiopulmonary function and clinical outcomes in patients with high-risk coronary syndrome and PH, offering a promising therapeutic strategy for this population. This study is a single-center retrospective study, which inherently limits the credibility of causal inference; therefore, the results need to be further verified by multi-center, large-sample prospective studies.