Korean J Clin Pharm.  2023 Dec;33(4):242-253. 10.24304/kjcp.2023.33.4.242.

Association of Arrhythmia in the Elderly Patients on Combination Therapy of CYP3A4 Substrates and Inhibitors with the Korean Claims Data

• Kim TW
• Chang J
• Choo E
• Park RW
• Lee S

• KMID: 2553204
• DOI: http://doi.org/10.24304/kjcp.2023.33.4.242

Abstract

Background
Arrhythmia due to QT prolongation is one of the most serious adverse events with drug interactions in the elderly. This study aimed to examine the incidence of arrhythmia in Korean elderly patients who administered both cytochrome P450 3A4 (CYP3A4) substrates and inhibitors.
Methods
Patients using CYP3A4 substrate and inhibitor were selected from the 2017 elderly patient dataset (the Korean Health Insurance Review and Assessment Service - Aged Population Sample). Selection criteria were patients with a medication possession ratio over 80%, medication duration of at least 7 days, and a follow-up period of 3 months or more. The patient’s basic information is age, gender, health insurance type, and comorbidities. The top 50 drug pairs and comorbidity with high-incidence arrhythmia were presented.
Results
In patien ts with drug combin ation s for over 7 days, there were 981 incidences of arrhythmia, and 351 incidences in those with combinations for over 30 days. The comorbidities of congestive heart failure and myocardial infarction had a significant association with incidence of arrhythmia. Among patients with 7 days or longer, the drug pairs [substrates-inhibitors] with significant adjusted odds ratio (aOR) were [propranolol-cimetidine] (aOR, 2.25; 95% confidence interval [CI], 1.66-3.04). Among patients with 30 days or longer, the drug pairs with significant aOR were [tramadolamiodarone] (aOR, 2.87; 95% CI, 1.97-4.19).
Conclusions
In elderly patients, the incidence of arrhythmia was high with drug interactions of CYP3A4 substrates and inhibitors. The comorbidity of congestive heart failure was the risk factor.

Keyword

Arrhythmias; cyp3a4 inhibitors; drug interaction; qt prolongation