Prevalence and factors associated with potential clinically significant drug-drug interactions in patients with cardiovascular diseases at hospital admission
Authors: Marović Iva , Udovičić Mario , Rudan Diana , Manola Šime , Samardžić Ivana , Vrca Vesna Bačić , Hadžiabdić Maja Ortner , Marinović Ivana 
Published: January 2025

Abstract
Cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity globally. It is estimated that 17.9 million people died from CVDs in 2019, which represents 32 % of all deaths worldwide. Cardiovascular drugs are the most common medical intervention for the prevention of cardiovascular events. CV medications have many benefits however their application is often complicated by multimorbidity and polypharmacy. Drug-drug interactions (DDIs) can lead to adverse drug events, hospitalizations, prolonged hospital stays, increased healthcare costs, and increased risk of mortality. Hospital admission provides an opportunity for pharmacotherapy analysis and for identifying DDIs which can jeopardize medication safety. The aim of this study is to determine the type and prevalence of potential clinically significant DDIs in patients with CVD and to examine factors associated with exposure to DDIs. A prospective study was conducted at the Dubrava University Hospital at the Clinic of Cardiology during a 6-month period (September 2023 – February 2024). Demographic, clinical and pharmacotherapy data were collected for each patient. The first prescribed pharmacotherapy was analyzed. The research was approved by the Hospital’s Ethics Committee and each patient involved in the study signed an informed consent. Lexicomp® Lexi-InteractTM Online (Lexi-Comp, Inc., USA) was used for DDI analysis. Poisson regression was used for regression analysis for determining risk factors associated with exposure to DDIs. Total of 151 patients admitted to Cardiology ward were included in the research, and the average age was 67 years. Patients had an average of 9 medications in their therapy and 8 diagnoses. Overall, 1268 potential clinically significant DDIs were determined, of which the most frequently determined interactions were grade C (90.9 %), then grade D (8.6 %) and grade X (0.6 %). CV medications were involved in 88 % DDIs. The most common interventions regarding identified DDIs included exclusion one of the drugs, dose adjustment, increased monitoring of signs of bleeding, cardiac disorders, hypoglycemia, CNS depression and rhabdomyolysis, blood pressure, markers of renal function and electrolyte status. Factors associated with the prevalence of potential clinically significant DDIs were decreased renal function, recent hospitalization, total number of comorbidities and polypharmacy. Specific comorbidities associated with DDIs were arrhythmia, heart failure, diabetes mellitus and disease of the respiratory system. A high prevalence of DDIs of CV medications in all categories of clinical significance was determined. Managing medication safety in specific patient groups with CVDs can represent a greater challenge regarding DDIs. Certain medical conditions, such as arrhythmia, heart failure, diabetes, and diseases of the respiratory system, multimorbidity, polypharmacy, impaired renal function and recent hospitalization are identified in this research as additional factors associated with DDIs occurrence in patients with CVDs at hospital admission. Hospital admission is one of the crucial points for managing medication safety. Clinical pharmacists should regularly analyze DDIs in prescribed pharmaco-therapy which enhances medication safety and also contributes to the quality of provided health care.