Prolongation of the QT interval in patients with coronary heart disease as consequence of drug-drug interactions on metabolic rate

Artur D Ismagilov,Zhanna M Sizova,Natalya N Shindryaeva,Evgeniya V Shikh

doi:10.29333/ejgm/93166

Abstract

Objective:Prolongation of the QT interval in patients with coronary heart disease (CAD) is a risk factor of polymorphic ventricular tachycardia (PVT) and as consequence, the sudden death. Drug-drug interactions (DDI) on metabolic rate involving cytochrome P-450 (CYP) is the one of the major cause of Long QT Syndrome (LQTS). The aim of the present study was to improve the safety of combined pharmacotherapy when using drugs that affect the QT interval.Method and Results:Medication occurrence of potential dangerous combination of medicines that are affected on QT interval duration in patients with CAD are researched (outpatient medical records (patient history) analysis). Clinical relevance of DDI, which are associated with changes in CYP enzyme activity, categorized by drugs.com Medication Guide. Finding potential dangerous combination of medicines that are affected on QT interval duration were administered to patients with CAD in 3.6% cases in outpatient clinical practice. The most often prescribed combination of drugs is amiodarone and torasemide (13.3% evidence of all concomitant administration that are leading to QT prolongation). The potential mechanism of Amiodarone and Torasemide interaction on metabolic rate that are leading to QT prolongation are competitive substrates CYP 2C8 and a result of inhibited CYP 2C9 by amiodarone.Conclusion:Ability to predict the prolongation of the QT interval caused by DDI on metabolic rate make possible to improve the safety concomitant administration to patients with CAD.

Highlights

There is a close attention in clinical cardiology that is given to the problem of QT prolongation as a risk factor of life-threatening cardiac arrhythmias – polymorphic ventricular tachycardia (PVT)
The analysis revealed that the QT prolongation was observed in 86 (9.2%) of 935 patients (54 men and 32 women, the average age is 57 ± 7.2 years), from whom a group of 34 (3, 6%) patients with coronary heart disease (CAD) with suspicion of prolongation of the QT interval was selected due to pharmacotherapy
Patients with coronary heart disease CAD were administered drugs ignoring prognosis for Drug-drug interactions (DDI), which are associated with changes in cytochrome P-450 (CYP) enzyme activity. 13.3% evidence of all concomitant administration with patients who have QT prolongation were prescribed a dangerous combination of Amiodarone and Torasemide

Summary

Introduction

There is a close attention in clinical cardiology that is given to the problem of QT prolongation as a risk factor of life-threatening cardiac arrhythmias – polymorphic ventricular tachycardia (PVT). Clinical aspects of the LQTS are proneness to arrhythmic syncope conditions and higher risk of developing fatal cardiac arrhythmias, mainly torsades de pointes (TdP) [1, 2]. The acquired variant of the LQTS is more common in daily clinical practice, which is usually connected with drug use. The list of such drugs is constantly updated on the website of the The Arizona Center for Education and Research on Therapeutics (AZCERT) organization (http://crediblemeds.org) [4]

Methods

Results

Conclusion