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. 2022 Feb;88(2):820-829.
doi: 10.1111/bcp.15030. Epub 2021 Aug 28.

Out-of-hospital cardiac arrest and differential risk of cardiac and non-cardiac QT-prolonging drugs in 37 000 cases

Talip E Eroglu  1   2   3 , Carlo A Barcella  3 , Marieke T Blom  1 , Grimur H Mohr  3 , Patrick C Souverein  2 , Christian Torp-Pedersen  3   4   5 , Fredrik Folke  3   6 , Mads Wissenberg  3   6 , Anthonius de Boer  2 , Peter J Schwartz  7 , Gunnar H Gislason  3   8   9 , Hanno L Tan  1   10 ; ESCAPE-NET Investigators
Affiliations

Out-of-hospital cardiac arrest and differential risk of cardiac and non-cardiac QT-prolonging drugs in 37 000 cases

Talip E Eroglu et al. Br J Clin Pharmacol. 2022 Feb.

Erratum in

  • Correction.
    [No authors listed] [No authors listed] Br J Clin Pharmacol. 2022 Aug;88(8):3924. doi: 10.1111/bcp.15424. Br J Clin Pharmacol. 2022. PMID: 35844182 Free PMC article. No abstract available.

Abstract

Aims: Drugs that prolong the QT interval, either by design (cardiac QT-prolonging drugs: anti-arrhythmics) or as off-target effect (non-cardiac QT-prolonging drugs), may increase the risk of ventricular arrhythmias and out-of-hospital cardiac arrest (OHCA). Risk mitigation measures were instituted, in particular, surrounding prescription of cardiac QT-prolonging drugs. We studied OHCA risk of both drug types in current clinical practice.

Methods: Using data from large population-based OHCA registries in the Netherlands and Denmark, we conducted two independent case-control studies. OHCA cases with presumed cardiac causes were matched on age/sex/index date with up to five non-OHCA controls. We calculated odds ratios (ORs) for the association of cardiac or non-cardiac QT-prolonging drugs with OHCA risk using conditional logistic regression analyses.

Results: We identified 2503 OHCA cases and 10 543 non-OHCA controls in the Netherlands, and 35 017 OHCA cases and 175 085 non-OHCA controls in Denmark. Compared to no use of QT-prolonging drugs, use of non-cardiac QT-prolonging drugs (Netherlands: cases: 3.0%, controls: 1.9%; Denmark: cases: 14.9%, controls: 7.5%) was associated with increased OHCA risk (Netherlands: OR 1.37 [95% CI: 1.03-1.81]; Denmark: OR 1.63 [95% CI: 1.57-1.70]). The association between cardiac QT-prolonging drugs (Netherlands: cases: 4.0%, controls: 2.5%; Denmark: cases: 2.1%, controls: 0.9%) and OHCA was weaker (Netherlands: OR 1.17 [95% CI: 0.92-1.50]; Denmark: OR 1.21 [95% CI: 1.09-1.33]), although users of cardiac QT-prolonging drugs had more medication use and comorbidities associated with OHCA risk than users of non-cardiac QT-prolonging drugs.

Conclusion: In clinical practice, cardiac QT-prolonging drugs confer lower OHCA risk than non-cardiac QT-prolonging drugs, although users of the former have higher a priori risk. This is likely due to risk mitigation measures surrounding prescription of cardiac QT-prolonging drugs.

Keywords: ESCAPE-NET; QT-prolonging drugs; epidemiology; sudden cardiac arrest.

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Conflict of interest statement

C.T.‐P. reports grants from Bayer and Novo Nordisk. F.F. reports grants from the Novo Nordisk Foundation. No other authors reported disclosures.

Figures

FIGURE 1
FIGURE 1
Flow chart of inclusion of out‐of‐hospital cardiac arrest cases in ARREST (A) and DANCAR (B) OHCA, out‐of‐hospital cardiac arrest; VT/VF, ventricular tachycardia/ventricular fibrillation
FIGURE 2
FIGURE 2
Risk of out‐of‐hospital arrest associated with use of cardiac or non‐cardiac QT‐prolonging drugs Not analysed: cases using both cardiac and non‐cardiac QT‐prolonging drugs in ARREST (n = 2) or DANCAR (n = 146). CI, confidence interval; OR, odds ratio. Numbers are number (%) unless indicated otherwise. In ARREST, effect estimates were adjusted for drug use, which served as proxies for comorbidities. In DANCAR we adjusted for both medication use and comorbidities. Error bars denote 95% confidence intervals
FIGURE 3
FIGURE 3
Risk of out‐of‐hospital cardiac arrest associated with use of individual drugs or types of QT‐prolonging drugs Not analysed: cases using other cardiac QT‐prolonging drugs or types of non‐cardiac QT‐prolonging drugs in ARREST (n = 3) or DANCAR (n = 432), and cases using more than one type of QT‐prolonging drug in ARREST (n = 9) or DANCAR (n = 839). CI, confidence interval; OR, odds ratio. In ARREST, effect estimates were adjusted for drug use, which served as proxies for comorbidities. In DANCAR we adjusted for both medication use and comorbidities. Numbers are number (%) unless indicated otherwise. Error bars denote 95% confidence intervals
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References

    1. Myerburg RJ, Castellanos A. Cardiac arrest and sudden cardiac death. In: Libby P, Bonow RO, Mann DL, Zipes DP, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. Oxford, UK: Elsevier; 2007:933‐974.
    1. Huikuri HV, Castellanos A, Myerburg RJ. Sudden death due to cardiac arrhythmias. N Engl J Med. 2001;345(20):1473‐1482. - PubMed
    1. Roden DM. Drug‐induced prolongation of the QT interval. N Engl J Med. 2004;350(10):1013‐1022. - PubMed
    1. The Cardiac Arrhythmia Suppression Trial (CAST) Investigators . Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med. 1989;321(6):406‐412. - PubMed
    1. Waldo AL, Camm AJ, DeRuyter H, et al. Effect of d‐sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. Lancet. 1996;348(9019):7‐12. - PubMed

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