Drug-Induced QTc Prolongation

Riad, Fady S.; Davis, Andrew M.; Moranville, Michael P.; Beshai, John F.

doi:10.1016/j.amjcard.2016.09.041

Cited by 23 publications

(26 citation statements)

References 15 publications

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“…In our analysis prolonged QTc, and QTc prolongation with concomitant AF, were associated with a two-fold and more than four-fold increased risk of all-cause mortality, respectively. Our findings add on and reinforce previous studies which demonstrated that long QTc is a risk factor for all-cause mortality [23,28,34]. Several studies confirmed this association among adult patients in different clinical settings, with risk of all-cause mortality approximately triplicated, as well in older patients [36][37][38][39][40].…”

Section: Discussionsupporting

confidence: 91%

“…Results did not differ analyzing separately typical and atypical antipsychotic drugs (data not shown). Although there is no doubt that antipsychotic drugs have the potential to cause arrhythmias, the ion channel effects of most drugs are relatively weak [30][31][32][33], and it is possible that these medications do not intrinsically prolong the QTc interval [34]. Moreover, QTc by itself is a weak predictor of torsade de pointes and sudden cardiac death [35], and there is no clear consensus on the correct approach for managing QT-prolonging risk with antipsychotics [30].…”

Section: Discussionmentioning

confidence: 99%

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Prevalence, predictors and clinical implications of prolonged corrected QT in elderly patients with dementia and suspected syncope

Bo¹,

Ceccofiglio

Mussi

et al. 2019

European Journal of Internal Medicine

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Background: Long QT and use of QT-prolonging drugs are common among older patients receiving polytherapies, but real-world evidence on their impact in clinical practice is controversial. We investigated prevalence, variables associated and clinical implications of prolonged corrected QT (QTc) among patients from the Syncope and Dementia study. Methods: Observational, prospective, multicenter study. Patients≥65 years with dementia and fall suspected for syncope in the previous three months were enrolled. Several clinical variables and the complete list of medications were recorded for each patient. A 12-lead ECG was obtained and corrected QT was calculated by the Bazett's formula. One-year followup for death and recurrent syncope was performed. Results: Prolonged QTc was observed in 25% of the 432 enrolled patients (mean age 83.3), and was significantly associated with male gender (OR 2.09; 95% CI 1.34-3.26) and diuretics use (OR 1.85; 95% CI 1.18-2.90). At one-year 23.3% of patients died and 30.4% reported at least one recurrent event. Variables associated with oneyear mortality were: age, male gender, atrial fibrillation (AF), use of calcium channel blockers and prolonged QTc (OR 1.80; 95% CI 1.01-3.20). Among patients with prolonged QTc a significant interaction for mortality was found with AF. Recurrent events were associated with the use of antiplatelets, cholinesterase. inhibitors and antipsychotics, but not with prolonged QTc. Conclusions: We documented a high prevalence of prolonged QTc, that was associated with male gender and diuretics but not with psychoactive medications. Patients with prolonged QTc had higher one-year mortality, that was four-fold increased in those with concomitant AF. 1. Introduction Long QT syndrome is an electro-physiologic disorder in which the ventricular repolarization is lengthened, with an increased susceptibility to ventricular tachy-arrhythmias, potentially leading to syncope, cardiac arrest and sudden cardiac death [1]. Acquired prolonged QT interval is the most common form of long QT syndrome, and usually results from the complex interplay between several factors

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Prevalence, predictors and clinical implications of prolonged corrected QT in elderly patients with dementia and suspected syncope

Bo¹,

Ceccofiglio

Mussi

et al. 2019

European Journal of Internal Medicine

View full text Add to dashboard Cite

show abstract

“…Kozik et al retrospectively analysed continuous ECG recordings of 88 patients during the first 72 hours of ICU admission and detected QTc interval> 500 ms in 46% (40/88) [ 23 ], while Ridruejo et al searched the hospital database of a medical ICU of 17 beds for a period of 7 years and identified only 88 cases of LQTS (> 450 ms for men and> 460 ms for women), among 9730 patients (0.9%) [ 24 ]. A retrospective study performed at an emergency department of a tertiary university for 3 months identified a prevalence of 35% (544/1558, 95% CI 32–37%), in which 8% had QTc greater than 500 ms (120/1558, 95% CI of 6 to 9%) [ 27 ], a result similar to that observed in another retrospective study, in which 38% (5650/14804) presented QTc> 450 ms for men and greater than 460 ms for women and 12% (1711/14804) had QTc> 500 ms [ 25 ].…”

Section: Discussionsupporting

confidence: 59%

“…Another study also observed that Bazzet’s formula overestimated the number of patients with prolonged QTc interval, while the Fridericia and Framingham formulas showed the best correction rate and significantly improved the prediction of mortality at 30 days and 1 year [ 14 ]. Despite this, Bazzet's formula continues to be widely used both in clinical practice and for research purposes [ 10 , 12 , 22 – 25 ], and so it was chosen as the QT interval correction formula in this study.…”

Section: Discussionmentioning

confidence: 99%

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QTc interval prolongation in critically ill patients: Prevalence, risk factors and associated medications

et al. 2018

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PurposeTo investigate the prevalence and risk factors of acquired long QT syndrome (LQTS) on admission to a general Intensive Care Unit (ICU), and to assess the risk of LQTS associated with prescribed medications.MethodsProspective observational, cross-sectional study approved by the Institutional Review Board. Between May 2014 and July 2016, 412 patients >18 years-old consecutively admitted to the ICU of a university hospital were included. LQTS was defined as a QT interval on the admission electrocardiogram corrected using Bazett’s formula (QTc) >460 ms for men and >470 ms for women. All medications administered within 24 hours before admission were recorded. Logistic regression was used.ResultsLQTS prevalence was 27.9%. In LQTS patients, 70.4% had ≥ 1 LQTS-inducing drug prescribed in the 24 hours prior to ICU admission versus 70.4% in non-LQTS patients (p = 0.99). Bradycardia and Charlson morbidity index score are independent risk factors for LQTS. Haloperidol (OR 4.416), amiodarone (OR 2.509) and furosemide (OR 1.895) were associated with LQTS, as well as another drug not yet described, namely clopidogrel (OR 2.241).ConclusionsThe LQTS is highly prevalent in critically ill patients, ICU patients are often admitted with LQTS-inducing medications, and patients with slow heart rate or with high Charlson comorbidity index should be evaluated for LQTS.

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Comparative risk of cardiac arrhythmias associated with acetylcholinesterase inhibitors used in treatment of dementias – A narrative review

Huang

Alsabbagh

2020

Pharmacology Res & Perspec

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Donepezil, galantamine, and rivastigmine are the three acetylcholinesterase inhibitors (AChEIs), out of a total of only four medications prescribed in the treatment of Alzheimer's Disease (AD) and related dementias. These medications are known to be associated with bradycardia given their mechanism of action of increasing acetylcholine (ACh). However, in March 2015, donepezil was added to the CredibleMeds “known‐risk” category, a list where medications have a documented risk for acquired long‐QT syndrome (ALQTS) and torsades de pointes (TdP) – a malignant ventricular arrhythmia that is a different adverse event than bradycardia (and is not necessarily associated with ACh action). The purpose of this article is to review the three AChEIs, especially with regards to mechanistic differences that may explain why only donepezil poses this risk; several pharmacological mechanisms may explain why. However, from an empirical point‐of‐view, aside from some case‐reports, only a limited number of studies have generated relevant information regarding AChEIs' and electrocardiogram findings; none have specifically compared donepezil against galantamine or rivastigmine for malignant arrhythmias such as TdP. Currently, the choice of one of the three AChEIs for treatment of AD symptoms is primarily dependent upon clinician and patient preference. However, clinicians should be aware of the potential increased risk associated with donepezil. There is a need to examine the comparative risk of malignant arrhythmias among AChEIs users in real‐world practice; this may have important implications with regards to changes in AChEI prescribing patterns.

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Drug-Induced QTc Prolongation

Cited by 23 publications

References 15 publications

Prevalence, predictors and clinical implications of prolonged corrected QT in elderly patients with dementia and suspected syncope

Prevalence, predictors and clinical implications of prolonged corrected QT in elderly patients with dementia and suspected syncope

QTc interval prolongation in critically ill patients: Prevalence, risk factors and associated medications

Comparative risk of cardiac arrhythmias associated with acetylcholinesterase inhibitors used in treatment of dementias – A narrative review

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