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      Identification of Patients At-Risk of QT Interval Prolongation during Medication Reviews: A Missed Opportunity?

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          Abstract

          The prolongation of the QT interval is a relatively rare but serious adverse drug reaction. It can lead to torsade de pointes, which is potentially life-threatening. The study’s objectives were: determine the use of QT interval-prolonging drugs in an elderly community-dwelling population at risk of medication misadventure and identify recommendations regarding the risk of QT interval prolongation made by pharmacists when performing medication reviews. In a retrospective evaluation, 500 medication review reports from Australian pharmacists were analysed. In patients taking at least one QT interval-prolonging drug, the individual risk of drug-induced QT interval prolongation was assessed. Recommendations of pharmacists to avoid the occurrence of this drug-related problem were examined. There was a high prevalence of use of potentially QT interval-prolonging drugs (71% patients), with 11% of patients taking at least one drug with a known risk. Pharmacists provided specific recommendations in only eight out of 35 patients (23%) with a high-risk score and taking drugs with known risk of QT interval prolongation. Pharmacists’ recommendations, when present, were focused on drugs with known risk of QT interval prolongation, rather than patients’ additional risk factors. There is a need to improve knowledge and awareness of this topic among pharmacists performing medication reviews.

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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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            Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management.

            Torsades de pointes (TdP) is a life-threatening arrhythmia associated with prolongation of the corrected QT (QTc) interval on the electrocardiogram. More than 100 drugs available in Canada, including widely used antibiotics, antidepressants, cardiovascular drugs and many others, may cause QTc interval prolongation and TdP. Risk factors for TdP include QTc interval >500 ms, increase in QTc interval ≥60 ms from the pretreatment value, advanced age, female sex, acute myocardial infarction, heart failure with reduced ejection fraction, hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, treatment with diuretics and elevated plasma concentrations of QTc interval-prolonging drugs due to drug interactions, inadequate dose adjustment of renally eliminated drugs in patients with kidney disease and rapid intravenous administration. Pharmacokinetic drug interactions associated with the highest risk of TdP include antifungal agents, macrolide antibiotics (except azithromycin) and drugs to treat human immunodeficiency virus interacting with amiodarone, disopyramide, dofetilide or pimozide. Other important pharmacokinetic interactions include antidepressants (bupropion, duloxetine, fluoxetine, paroxetine) interacting with flecainide, quinidine or thioridazine. Pharmacists play an important role in minimizing the risk of drug-induced QTc interval prolongation and TdP through knowledge of drugs that are associated with a known or possible risk of TdP, individualized assessment of risk of drug-induced QTc interval prolongation, awareness of drug interactions most likely to result in TdP and attention to dose reduction of renally eliminated QTc interval-prolonging drugs in patients with kidney disease. Treatment of hemodynamically stable TdP consists of discontinuation of the offending drug(s), correction of electrolyte abnormalities and administration of intravenous magnesium sulfate 1 to 2 g.
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              Risk factors for QTc-prolongation: systematic review of the evidence.

              Background QTc-interval prolongation has been associated with serious adverse events, such as Torsade de Pointes and sudden cardiac death. In the prevention of QTc-prolongation, special attention should go to high-risk patients. Aim of the review The aim of this review is to summarize and assess the evidence for different risk factors for QTc-prolongation (demographic factors, comorbidities, electrolytes, QTc-prolonging medication). Methods Potential studies were retrieved based on a systematic search of articles published until June 2015 in the databases Medline and Embase. Both terms about QTc-prolongation/Torsade de Pointes and risk factors were added in the search strategy. The following inclusion criteria were applied: randomized controlled trials and observational studies; inclusion of ≥500 patients from a general population (not limited to specific disease states); assessment of association between QTc-interval and risk factors. For the articles that met the inclusion criteria, the following data were extracted: study design, setting and study population, number of patients and cases of QTc-prolongation, method of electrocardiogram-monitoring, QTc-correction formula, definition of QTc-prolongation, statistical methods and results. Quality assessment was performed using the GRADE approach (for randomized controlled trials) and the STROBE-recommendations (for observational studies). Based on the number of significant results and the level of significance, a quotation of the evidence was allocated. Results Ten observational studies could be included, with a total of 89,532 patients [prospective cohort design: N = 6; multiple regression analyses: N = 5; median STROBE score = 17/22 (range 15-18)]. Very strong evidence was found for hypokalemia, use of diuretics, antiarrhythmic drugs and QTc-prolonging drugs of list 1 of CredibleMeds. Little or no evidence was found for hyperlipidemia, the use of digoxin or statins, neurological disorders, diabetes, renal failure, depression, alcohol abuse, heart rate, pulmonary disorders, hormone replacement therapy, hypomagnesemia, history of a prolonged QTc-interval/Torsade de Pointes, familial history of cardiovascular disease, and the use of only QTc-prolonging drugs of list 2 or 3 of CredibleMeds. Conclusion This systematic review gives a clear overview of the available evidence for a broad range of risk factors for QTc-prolongation.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                10 December 2018
                December 2018
                : 7
                : 12
                : 533
                Affiliations
                [1 ]Faculty of Health, University of Canberra, Bruce, ACT 2617, Australia; Vera.Buss@ 123456canberra.edu.au (V.H.B.); kaylalee_@ 123456live.com.au (K.L.); Mark.Naunton@ 123456canberra.edu.au (M.N.); G.Peterson@ 123456utas.edu.au (G.M.P.)
                [2 ]School of Medicine, University of Tasmania, Sandy Bay, TAS 7005, Australia
                Author notes
                [* ]Correspondence: Sam.Kosari@ 123456canberra.edu.au ; Tel.: +61-(0)2-6201-2158
                Author information
                https://orcid.org/0000-0001-9963-8693
                https://orcid.org/0000-0002-6422-7170
                https://orcid.org/0000-0002-6764-3882
                https://orcid.org/0000-0002-6737-1442
                Article
                jcm-07-00533
                10.3390/jcm7120533
                6306817
                30544669
                b7748e01-76d5-438b-8152-b4534a5a050d
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 07 November 2018
                : 07 December 2018
                Categories
                Article

                qt interval prolongation,torsade de pointes,medication review,pharmacist intervention

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