Drug–Drug Interactions vs. Therapeutic Combinations in Patients with Congestive Heart Failure and Diabetes: An Ambispective Real‐World Study

Concomitant congestive heart failure (CHF) and diabetes mellitus (DM) patients frequently are treated with polypharmacy, thus potentially increasing the risk of drug-drug interactions (pDDIs). Conventional DDI screening methods often fail to distinguish clinically significant interactions from recommended therapeutic combinations. This study assessed the prevalence, severity, and clinical consequences of pDDIs in hospitalized patients with CHF and DM. This ambispective, cross-sectional study included 144 hospitalized patients with CHF and DM. We used the Micromedex and Lexicomp databases to check prescriptions. We classified clinically relevant DDIs and therapeutic combinations requiring routine monitoring by severity. 207 pDDIs were identified, of which 84.1% were moderate and 15.9% severe. Polypharmacy was a major risk factor for the DDI burden, and over seven drugs were associated with significantly more interactions than fewer drugs (P < 0.001). Polypharmacy was an independent predictor of clinically significant DDI (AOR 3.42; 95% CI 1.78-6.59) in the multivariate analysis. The most commonly seen combinations (statin-ezetimibe and sulfonylurea-metformin therapy) are guideline-recommended and do not need to be avoided. Clinical pharmacists and prescribing clinicians performing context-aware interpretation of DDI alerts by differentiating between guideline-recommended therapeutic combinations requiring monitoring and truly actionable interactions can reduce alert fatigue, preserve evidence-based therapy, and support safe prescribing in complex CHF-DM patients.