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

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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.

OriginalsprogEngelsk
TidsskriftBritish Journal of Clinical Pharmacology
Vol/bind88
Udgave nummer2
Sider (fra-til)820-829
Antal sider10
ISSN0306-5251
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
The authors greatly appreciate the contributions of Paulien Homma, Remy Stieglis and Sandra de Haas for data management of the ARREST registry, and are greatly indebted to all participating EMS dispatch centres (Amsterdam, Haarlem and Alkmaar), regional ambulance services (Ambulance Amsterdam, GGD Kennemerland, Witte Kruis and Veiligheidsregio Noord-Holland Noord Ambulancezorg), fire brigades and police departments in the study region for their contribution and support. The authors would also like to thank the pharmacists, PHARMO Database Network and Stichting Farmaceutische Kerngetallen. For completion of the case reports which form the Danish Cardiac Arrest Registry, the authors thank the Danish Emergency Medical Services. This project has received funding from the European Union's Horizon 2020 research and innovation programme under the acronym ESCAPE-NET, registered under grant agreement No. 733381 (T.E.E., M.T.B., H.L.T.), the COST Action PARQ (grant agreement No. CA19137) supported by COST (European Cooperation in Science and Technology), and the Dutch Heart Foundation (CVON2017–15 RESCUED and CVON2018–30 Predict-2; M.T.B., H.L.T.). The Danish Cardiac Arrest Registry was supported by Trygfonden.

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

Funding Information:
The authors greatly appreciate the contributions of Paulien Homma, Remy Stieglis and Sandra de Haas for data management of the ARREST registry, and are greatly indebted to all participating EMS dispatch centres (Amsterdam, Haarlem and Alkmaar), regional ambulance services (Ambulance Amsterdam, GGD Kennemerland, Witte Kruis and Veiligheidsregio Noord‐Holland Noord Ambulancezorg), fire brigades and police departments in the study region for their contribution and support. The authors would also like to thank the pharmacists, PHARMO Database Network and Stichting Farmaceutische Kerngetallen. For completion of the case reports which form the Danish Cardiac Arrest Registry, the authors thank the Danish Emergency Medical Services. This project has received funding from the European Union's Horizon 2020 research and innovation programme under the acronym ESCAPE‐NET, registered under grant agreement No. 733381 (T.E.E., M.T.B., H.L.T.), the COST Action PARQ (grant agreement No. CA19137) supported by COST (European Cooperation in Science and Technology), and the Dutch Heart Foundation (CVON2017–15 RESCUED and CVON2018–30 Predict‐2; M.T.B., H.L.T.). The Danish Cardiac Arrest Registry was supported by Trygfonden.

Publisher Copyright:
© 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

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