Objective To investigate the effect of combined treatment of meglumine cyclic adenosine monophosphate and digoxin on patients with chronic pulmonary heart disease (CPHD) accompanied by heart failure, and analyze its clinical safety. Methods A retrospective collection of 47 patients with CPHD accompanied by heart failure who were treated with combination therapy of meglumine cyclic adenosine monophosphate and digoxin on the basis of conventional treatment in our hospital from July 2021 to July 2024 was used as the study group. A control group of 47 patients with CPHD accompanied by heart failure treated with digoxin during the same period was collected. The clinical efficacy and adverse reactions of the two groups were compared, as well as the cardiac function indicators, serum cardiac function injury indicators, and serum inflammatory factor indicators [N-terminal pro-brain natriuretic peptide (NT-proBNP), interleukin-6 (IL-6), creatine kinase isoenzyme (CK-MB), Cardiac troponinⅠ (cTnI), and high-sensitivity C-reactive protein (hs-CRP)] before and after treatment. Results The total effective rate of the study group (91.49%) was higher than that of the control group (72.34%) (P<0.05). After treatment, the left ventricular ejection fraction (LVEF) level in the study group was higher than that in the control group, while the left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV) levels were lower than those in the control group (P<0.05). The levels of serum NT-proBNP, CK-MB, cTnⅠ, IL-6, and hs-CRP in the study group after treatment were lower than those in the control group (P<0.05). There was no significant difference in the total incidence of adverse reactions between the study group and the control group (P>0.05). Conclusion The combined treatment of meglumine cyclic adenosine monophosphate and digoxin in patients with CPHD accompanied by heart failure can effectively reduce cardiac function damage and inflammatory response, promote the improvement of cardiac function, and enhance the efficacy, with reliable safety.