Predictors of drug–drug interactions in patients with heart failure

A BSTRACT Introduction: Heart failure (HF) patients are frequently exposed to polypharmacy, placing them at increased risk for drug–drug interactions (DDIs), especially in an outpatient setting where monitoring may be limited. The aim was to assess the prevalence and predictors of clinically relevant DDIs in HF patients and identify patterns associated with higher interaction risk. Methods: This cross-sectional observational study included 670 HF patients, treated at a single outpatient cardiology practice. Clinical and pharmacologic data were extracted from medical records. DDIs were identified using the Epocrates interaction checker and classified by severity. Logistic regression and generalized linear models were used to evaluate predictors of avoidable and monitor-required interactions. Results: No contraindicated DDIs were found, but 72.7% of patients had at least one avoidable interaction, and 100% had at least one requiring monitoring. Anticoagulants, mineralocorticoid receptor antagonists, proton pump inhibitor (PPI) use, older age, and HFmrEF and HFpEF phenotypes were significantly associated with increased risk of clinically relevant DDIs. Polypharmacy strongly influenced interaction burden, particularly when ramipril, metformin, atorvastatin, SGLT2 inhibitors, or PPIs were prescribed. Beta-blockers were mildly protective. Conclusion: Clinically significant DDIs are common in HF patients in outpatient care. Risk is highest in older patients, patients with comorbidities requiring multiple pharmacological agents, regimens, and patients with HFmrEF and HFpEF. Structured medication review and attention to high-risk drug combinations are essential to improve safety in HF pharmacotherapy.