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      Co-Prescription of QT-Interval Prolonging Drugs: An Analysis in a Large Cohort of Geriatric Patients

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          Abstract

          Background

          Drug-induced QT-interval prolongation is associated with occurrence of potentially fatal Torsades de Pointes arrhythmias (TdP). So far, data regarding the overall burden of QT-interval prolonging drugs (QT-drugs) in geriatric patients are limited.

          Objective

          This study was performed to assess the individual burden of QT-interval prolonging drugs (QT-drugs) in geriatric polymedicated patients and to identify the most frequent and risky combinations of QT-drugs.

          Methods

          In the discharge medication of geriatric patients between July 2009 and June 2013 from the Geriatrics in Bavaria–Database (GiB-DAT) (co)-prescriptions of QT-drugs were investigated. QT-drugs were classified according to a publicly available reference site (CredibleMeds ®) as ALL-QT-drugs (associated with any QT-risk) or High-risk-QT-drugs (corresponding to QT-drugs with known risk of Torsades de Pointes according to CredibleMeds ®) and in addition as SmPC-high-risk-QT-drugs (according to the German prescribing information (SmPC) contraindicated co-prescription with other QT-drugs).

          Results

          Of a cohort of 130,434 geriatric patients (mean age 81 years, 67% women), prescribed a median of 8 drugs, 76,594 patients (58.7%) received at least one ALL-QT-drug. Co-prescriptions of two or more ALL-QT-drugs were observed in 28,768 (22.1%) patients. Particularly risky co-prescriptions of High-risk-QT-drugs or SmPC-high-risk-QT-drugs with at least on further QT-drug occurred in 55.9% (N = 12,633) and 54.2% (N = 12,429) of these patients, respectively. Consideration of SmPCs (SmPC-high-risk-QT-drugs) allowed the identification of an additional 15% (N = 3,999) patients taking a risky combination that was not covered by the commonly used CredibleMeds ® classification. Only 20 drug-drug combinations accounted for more than 90% of these potentially most dangerous co-prescriptions.

          Conclusion

          In a geriatric study population co-prescriptions of two and more QT-drugs were common. A considerable proportion of QT-drugs with higher risk only could be detected by using more than one classification-system. Local adaption of international classifications can improve identification of patients at risk.

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          Most cited references38

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          Development and validation of a risk score to predict QT interval prolongation in hospitalized patients.

          Identifying hospitalized patients at risk for QT interval prolongation could lead to interventions to reduce the risk of torsades de pointes. Our objective was to develop and validate a risk score for QT prolongation in hospitalized patients.
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            Drug-induced long QT syndrome.

            The drug-induced long QT syndrome is a distinct clinical entity that has evolved from an electrophysiologic curiosity to a centerpiece in drug regulation and development. This evolution reflects an increasing recognition that a rare adverse drug effect can profoundly upset the balance between benefit and risk that goes into the prescription of a drug by an individual practitioner as well as the approval of a new drug entity by a regulatory agency. This review will outline how defining the central mechanism, block of the cardiac delayed-rectifier potassium current I(Kr), has contributed to defining risk in patients and in populations. Models for studying risk, and understanding the way in which clinical risk factors modulate cardiac repolarization at the molecular level are discussed. Finally, the role of genetic variants in modulating risk is described.
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              QT interval prolongation and the risk of torsades de pointes: essentials for clinicians.

              QT interval prolongation signifies an increased risk of the life-threatening arrhythmia torsades de pointes (TdP). The purpose of this paper is to review the diverse methods for assessing and monitoring the risk of TdP, discuss risk factors for TdP, and recommend interventions that may mitigate the risk of TdP.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                18 May 2016
                2016
                : 11
                : 5
                : e0155649
                Affiliations
                [1 ]Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
                [2 ]Geriatrics in Bavaria–Database (Geriatrie in Bayern-Datenbank, GiB-DAT), Nürnberg, Germany
                [3 ]Geriatrics Center Erlangen, Waldkrankenhaus St. Marien gGmbH, Erlangen, Germany
                University of Bologna & Italian Institute of Technology, ITALY
                Author notes

                Competing Interests: SS, RM, & TT declared no conflict of interest. KGG reported receiving payments for lectures from Pfizer and Bristol-Myers Squibb. MFF reported receiving personal compensation from Boehringer Ingelheim Pharma for expert testimony and payments for lectures from Bayer-Schering Pharma, Boehringer Ingelheim Pharma, Janssen Cilag, Sanofi-Aventis Deutschland, and Merck. The Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg, received compensation from Merck and Sanofi-Aventis Deutschland for commissioned research by MFF’s group and from Gilead for supplies for in vitro studies. The authors' competing interests do not alter their adherence to PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: SS KGG MFF RM. Performed the experiments: SS TT KGG MFF RM. Analyzed the data: SS TT RM. Wrote the paper: SS KGG MFF RM.

                Article
                PONE-D-16-03710
                10.1371/journal.pone.0155649
                4871413
                27192430
                921b161d-98ac-43de-9910-04d779b24c45
                © 2016 Schächtele et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 27 January 2016
                : 2 May 2016
                Page count
                Figures: 4, Tables: 3, Pages: 19
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article
                Medicine and Health Sciences
                Pharmacology
                Drug Interactions
                Drug-Drug Interactions
                Medicine and Health Sciences
                Geriatrics
                Medicine and Health Sciences
                Pharmacology
                Drug Interactions
                Medicine and Health Sciences
                Cardiology
                Arrhythmia
                Medicine and Health Sciences
                Geriatrics
                Geriatric Rehabilitation
                Medicine and Health Sciences
                Rehabilitation Medicine
                Geriatric Rehabilitation
                Medicine and Health Sciences
                Health Care
                Health Care Providers
                Medical Doctors
                Physicians
                People and Places
                Population Groupings
                Professions
                Medical Doctors
                Physicians
                Medicine and Health Sciences
                Pharmacology
                Drug Information
                People and Places
                Population Groupings
                Ethnicities
                German People
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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