Polypharmacy as a Major Determinant of Drug–Drug Interactions in Patients with Acute Myocardial Infarction: A Prospective Observational Study

Abstract

Background: Potential drug–drug interactions (pDDIs) are a major patient-safety concern in acute coronary syndrome (ACS) management, where complex, guideline-mandated polypharmacy is unavoidable. Despite the well-recognised hazard, systematic pharmacovigilance data from resource-limited, tertiary-care settings in low- and middle-income countries remain scarce.

Objective: To identify and classify all potential DDIs in hospitalised acute myocardial infarction (MI) patients using the Lexicomp® Drug Interaction Database, and to evaluate the association of DDI burden with patient demographic and clinical characteristics.

Methods: A cross-sectional study was conducted on 35 consecutive patients admitted with acute MI across five districts of Khyber Pakhtunkhwa, Pakistan. All prescribed medications were recorded and analysed using the Lexicomp® interaction database (Rating A–X). Statistical analyses included the Shapiro–Wilk normality test, Mann–Whitney U test, Kruskal–Wallis H-test with Bonferroni-corrected post-hoc comparisons, Spearman rank correlation, chi-square, and Fisher's exact tests (α = 0.05).

Results: A total of 139 potential DDIs were identified; DDI prevalence was 100%. The mean number of DDIs per patient was 3.97 ± 1.99 (95% CI: 3.31–4.63). Of these, 38 (27.3%) were Major (Lexicomp Rating D), 63 (45.3%) Moderate (Rating C), and 38 (27.3%) Minor (Rating B). Ninety-four point three percent of patients harboured ≥1 major interaction. The most frequent high-risk pair was enoxaparin combined with dual antiplatelet therapy (aspirin + clopidogrel), occurring in 85.7% of patients. A very strong, statistically significant positive correlation was found between the number of co-prescribed drugs and total DDI count (ρ = 0.899, p < 0.001). No significant associations were identified for sex (U = 120.5, p = 0.908), age group (H = 2.22, p = 0.529), or diagnosis type (H = 1.69, p = 0.639).

Conclusion: Potential DDIs are virtually universal in ACS patients managed with guideline-based pharmacotherapy. Polypharmacy, rather than patient demographic characteristics, is the primary determinant of DDI accumulation. Systematic DDI screening using validated clinical tools should be integrated into routine ACS care, particularly in resource-constrained settings where pharmacist-led review remains limited.