In a nationwide registry-based cohort study with 2-year follow-up, investigators evaluated the prevalence and clinical associations of potentially clinically significant drug–drug interactions (DDIs) in adults aged ≥65 years with atrial fibrillation (AF), at least one comorbidity, and prescribed two or more medications. The cohort included 192,716 individuals identified from Swedish national registers as of 1 January 2017. The results were published in the Cardiovascular Drugs and Therapy.

Overall, 37.5% had at least one potential DDI. Cardiovascular drugs (33.8%) and central nervous system (CNS) drugs (12.4%) were most frequently involved. Sex, age, and civil status were consistently associated with DDI occurrence.

In Cox regression analyses, presence of at least one DDI was associated with higher hazards of cardiovascular (CV) death (hazard ratio [HR] 1.28; 95% CI 1.24–1.32), CV hospitalization (HR 1.12; 95% CI 1.10–1.15), and falls (HR 1.06; 95% CI 1.02–1.09). DDIs involving direct oral anticoagulants were associated with gastrointestinal bleeding (HR 2.80; 95% CI 1.35–5.81). DDIs involving CNS drugs were associated with stroke (HR 1.19; 95% CI 1.09–1.29) and falls (HR 1.32; 95% CI 1.27–1.39).

Potentially clinically significant DDIs were common and associated with adverse clinical outcomes in this older AF population. Identification of high-risk groups may inform preventive strategies and clinical management.