Abstract
PURPOSE: Coronary heart disease (CHD) is accompanied by a high level of comorbidity, which necessitates the use of complex treatment regimens in pharmacotherapy. In such cases, multicomponent pharmacotherapy significantly increases the risk of pharmacological interactions, which can result in either enhanced therapeutic effects (synergism) or adverse outcomes (antagonism, toxic effects). These drug interactions may influence the level of adherence to treatment in patients with CHD with comorbid conditions. PURPOSE OF THE STUDY: To assess the systemic impact of potential drug-drug interactions (pDDI), classified by type of pharmacodynamic response (synergism, antagonism, toxicity), on adherence to pharmacotherapy in patients with CHD with comorbid conditions, with subsequent prediction of risks associated with reduced adherence to treatment. MATERIALS AND METHODS: The study examined medical data of patients with CHD with comorbid conditions (n = 145) based on the analysis of prescriptions from hospital medical records for pDDI using standardized databases Medscape and Drugs.com. This study is cross-sectional, as it involved a single analysis of complex treatment regimens for drug compatibility and patient surveys conducted within the defined time frame (from October 2024 to June 2025). A survey of patients was conducted to determine adherence to pharmacotherapy of CHD with comorbid conditions using the standardized Medication Adherence Report Scale (MARS-5) scale. Nonparametric statistical methods were used, Spearman correlation analysis, ordinal logistic regression, and prediction to establish associations and determine the impact between pDDIs present in pharmacotherapy of CHD with comorbid conditions in prescriptions for pharmacological synergism, antagonism, and toxic effects due to pDDIs on adherence to treatment. Retrospective, clinical-epidemiological, frequency, content analyses, comparisons, and generalizations were used. RESULTS: Unacceptable polypharmacy was identified in 95.86% of cases within the studied cohort. A strong positive correlation was noted between the number of pDDIs and pharmacodynamic synergism (rs = 0.738), antagonism (rs = 0.659), and toxic effects (rs = 0.554). The number of concurrently administered medications was associated with a proportional increase in pDDIs, reflecting fundamental principles of clinical pharmacology. Results from the Kruskal-Wallis test revealed statistically significant differences in the number of pDDIs among patient groups with varying levels of adherence to pharmacotherapy (Kruskal-Wallis H = 7.31, p = 0.0258). Notably, each unit increase (one drug prescription) in pharmacodynamic antagonism was associated with a 1.74-fold higher likelihood of non-adherence to treatment, holding other variables constant in the adherence model. Furthermore, higher levels of pharmacodynamic antagonism and toxic effects resulting from pDDIs were correlated with greater likelihood of refusal to continue pharmacotherapy. Specifically, each unit increase in drug-induced toxic effects due to pDDI was linked to a 1.36-fold increase in the probability of low treatment adherence, assuming the fixed effect of other model variables. Pharmacodynamic antagonism and toxic effects attributable to pDDIs are key determinants of reduced adherence to pharmacotherapy in patients with CHD with comorbidities. The increased probability of antagonistic or toxic interactions due to pDDIs indirectly diminishes patients' willingness to comply with medication and treatment regimens. CONCLUSION: Pharmacological pDDIs due to pharmacodynamic antagonism (OR ~ 1.74) and toxic effects resulting from pDDIs (OR ~ 1.36) significantly increase the risk of low adherence to treatment. The identified risks can be minimized by implementing a multidisciplinary approach to providing medical care and involving clinical pharmacists in the quality control of complex prescription regimens and in optimizing pharmacotherapy of CHD with comorbid conditions.