Cases of drug-induced Torsade de Pointes: a review of Belgian cases in the EudraVigilance database

Vandael, Eline; Vandenberk, Bert; Vandenberghe, Joris; Willems, Rik; Foulon, Veerle

doi:10.1080/17843286.2017.1300217

Cited by 11 publications

(8 citation statements)

References 14 publications

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“…Advanced age is a recognised risk factor for the development of TdP associated with the use of QTc-prolonging drugs 1 4 11 12. Ageing is also associated with polypharmacy—in Sweden, people aged ≥75 years are prescribed on average five different drugs20—and there is comprehensive evidence that concomitant administration of more than one TdP-classified drug further increases the risk of developing a QTc prolongation and TdP 3 4 21–25. Our results are confirmative in this aspect.…”

Section: Discussionsupporting

confidence: 78%

“…Yet another reason is probably a low reporting rate by healthcare professionals. In general, only a few per cent of adverse drug reactions (ADRs) are reported to the competent authorities; for example, only 1% of hospitalisations caused by ADRs are reported in the Netherlands 21. It is for the abovementioned reasons that it is very difficult to retrospectively make a TdP diagnosis, even if suspicions may exist; for example, an older woman treated with a drug with known TdP risk suddenly dies at home in connection with a gastroenteritis (which can cause electrolyte changes).…”

Section: Discussionmentioning

confidence: 99%

“…Such systems can create patient-specific alerts that automatically take into account the individual risk factors of the patient. These alerts can make the risk management of QTc prolongation and TdP more feasible, and closer monitoring can be limited to high-risk patients, as discussed by Vandael et al 21…”

Section: Discussionmentioning

confidence: 99%

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Drug use and torsades de pointes cardiac arrhythmias in Sweden: a nationwide register-based cohort study

et al. 2020

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ObjectiveTo study the occurrence of torsades de pointes (TdP) ventricular tachycardia in relation to use of drugs labelled with TdP risk, using two nationwide Swedish registers.DesignProspective register-based cohort study.SettingEntire Sweden.ParticipantsPersons aged ≥18 years prescribed and dispensed any drug classified with TdP risk during 2006–2017, according to CredibleMeds. Persons with a registered TdP diagnosis during the study period, using drugs labelled with known (TdP 1), possible (TdP 2) or conditional (TdP 3) risk at the incident of TdP were examined.Primary outcome measuresOccurrence of TdP in relation to exposure rates for individual drugs with TdP risk.Secondary outcome measuresConcurrent use of more than one TdP-labelled drug in a person with a TdP diagnosis.ResultsDuring the study period, 410 TdP cases using drugs with TdP risk labels at the incident were registered; 205 women and 205 men, mean age 74.0 and 71.5 years, respectively. Antidepressants dominated (129/410, 30%), followed by antiarrhythmics (17%). Diuretics and gastric acid-secretion inhibitors, with TdP risk related to induction of hypokalaemia or hypomagnesaemia, were used in 56% and 32% of the 410 TdP cases, respectively. Among the most used antidepressants, citalopram with known TdP 1 risk was associated with both a higher absolute number and incidence of TdP per 100 000 users (two to four times), compared with mirtazapine with possible (TdP 2), and sertraline with conditional (TdP 3) risk. Multiple risk factors, including advanced age, cardiovascular disease and treatment with more than one TdP-classified drug, were frequently observed.ConclusionsAntidepressants followed by antiarrhythmics dominated among TdP risk drugs used by adults with TdP diagnosis, the majority being ≥65 years. TdP risk class and concomitant medication should be considered when prescribing antidepressants to older patients.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

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Drug use and torsades de pointes cardiac arrhythmias in Sweden: a nationwide register-based cohort study

et al. 2020

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“…A retrospective case-control study that quantified the risk of cardiac arrest related to the use of non-arrhythmic LQTS inducers in 140 patients resuscitated from cardiac arrest at a Dutch university hospital found an increased risk of arrest associated with the number of prescribed LQTS-associated drugs (OR 4.8; 95% CI 1.6-14) [28]. Drug interactions also represented a high proportion of cases of drug-induced TdP within a Belgium study using the EudraVigilance database (18/31 cases) [29]. However, some evidence in the literature is conflicting.…”

Section: Discussionmentioning

confidence: 99%

Drug-Associated QTc Prolongation in Geriatric Hospitalized Patients: A Cross-Sectional Study in Internal Medicine

Rossi

Marzi

Natale

et al. 2021

Drugs - Real World Outcomes

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Objective The primary objectives of this prospective cross-sectional study were to estimate the prevalence of drug-related long QT syndrome (LQTS) and the prevalence of use of QT-prolonging drugs in older patients admitted to an internal medicine unit. Methods We screened consecutive patients hospitalized in an internal medicine unit over a 2-year period. A 12-lead electrocardiogram using an electrocardiograph with automated measurement of QT interval was recorded. Patient characteristics (age, sex, body mass index), drug treatments, and variables associated with QT interval prolongation, including hypothyroidism, type 2 diabetes mellitus, and cardiac disease, were also recorded. In addition, we also measured serum levels of potassium, calcium, magnesium, and creatinine at admission. The list of medications known to cause or to contribute to LQTS was obtained from CredibleMeds ® . Results A total of 243 patients were enrolled: mean ± standard deviation age, 79.65 ± 8.27 years; males, n = 121 (40.8%); mean corrected QT (QTc) interval, 453.70 ± 43.77 ms. Overall, 89/243 (36.6%) patients had a prolonged QTc interval, with 29/243 (11.9%) having QTc interval prolongation > 500 ms (11.9%). A vast majority were prescribed at least one QT-prolonging drug (218/243 [89.7%]), whereas 74/218 (30.5%) were receiving at least one medication with a known risk of Torsades des Pointes (TdP). Proton pump inhibitors were the second most commonly prescribed class of drugs. After logistic regression, male sex was independently associated with LQTS (odds ratio 2.85; 95% confidence interval 1.56-5.22; p = 0.001). Conclusions The prevalence of LQTS with QTc interval > 500 ms in geriatric inpatients was > 10%, and QT-prolonging drugs were frequently used on admission (more than 30% of patients were receiving drugs with a known risk of TdP).Franco Laghi-Pasini: Retired.

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“… 41 Drug interactions were also reported to represent a high proportion of cases of drug-induced TdP within a Belgium study using the EudraVigilance database (18 of 31 cases). 42 …”

Section: Discussionmentioning

confidence: 99%

Drugs and life-threatening ventricular arrhythmia risk: results from the DARE study cohort

et al. 2017

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ObjectivesTo establish a unique sample of proarrhythmia cases, determine the characteristics of cases and estimate the contribution of individual drugs to the incidence of proarrhythmia within these cases.SettingSuspected proarrhythmia cases were referred by cardiologists across England between 2003 and 2011. Information on demography, symptoms, prior medical and drug histories and data from hospital notes were collected.ParticipantsTwo expert cardiologists reviewed data for 293 referred cases: 130 were included. Inclusion criteria were new onset or exacerbation of pre-existing ventricular arrhythmias, QTc >500 ms, QTc >450 ms (men) or >470 ms (women) with cardiac syncope, all secondary to drug administration. Exclusion criteria were acute ischaemia and ischaemic polymorphic ventricular tachycardia at presentation, structural heart disease, consent withdrawn or deceased prior to study. Descriptive analysis of Caucasian cases (95% of included cases, n=124) and culpable drug exposures was performed.ResultsOf the 124 Caucasian cases, 95 (77%) were QTc interval prolongation-related; mean age was 62 years (SD 15), and 63% were female. Cardiovascular comorbidities included hypertension (53%) and patient-reported ‘heart rhythm problems’ (73%). Family history of sudden death (36%) and hypokalaemia at presentation (27%) were common. 165 culpable drug exposures were reported, including antiarrhythmics (42%), of which amiodarone and flecainide were the most common. Sotalol, a beta-blocking agent with antiarrhythmic activity, was also common (15%). 26% reported multiple drugs, of which 84% reported at least one cytochrome (CYP) P450 inhibitor. Potential pharmacodynamics interactions identified were mainly QT prolongation (59%).ConclusionsAntiarrhythmics, non-cardiac drugs and drug combinations were found to be culpable in a large cohort of 124 clinically validated proarrhythmia cases. Potential clinical factors that may warn the prescriber of potential proarrhythmia include older women, underlying cardiovascular comorbidity, family history of sudden death and hypokalaemia.

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Cases of drug-induced Torsade de Pointes: a review of Belgian cases in the EudraVigilance database

Cited by 11 publications

References 14 publications

Drug use and torsades de pointes cardiac arrhythmias in Sweden: a nationwide register-based cohort study

Drug use and torsades de pointes cardiac arrhythmias in Sweden: a nationwide register-based cohort study

Drug-Associated QTc Prolongation in Geriatric Hospitalized Patients: A Cross-Sectional Study in Internal Medicine

Drugs and life-threatening ventricular arrhythmia risk: results from the DARE study cohort

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