TY - JOUR

T1 - Opioid use is associated with increased out-of-hospital cardiac arrest risk among 40 000-cases across two countries

AU - Eroglu, Talip E.

AU - Barcella, Carlo A.

AU - Blom, Marieke T.

AU - Souverein, Patrick C.

AU - Mohr, Grimur H.

AU - Torp-Pedersen, Christian

AU - Folke, Fredrik

AU - Wissenberg, Mads

AU - de Boer, Anthonius

AU - Gislason, Gunnar H.

AU - Tan, Hanno L.

AU - for the ESCAPE-NET Investigators

N1 - 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 PHARMO Database Network, Stichting Farmaceutische Kerngetallen and the pharmacists for the participation in this study. For completion of the case reports which form the Danish Cardiac Arrest Registry, the authors thank the Danish Emergency Medical Services. This work was supported by 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 Netherlands Cardio Vascular Research Initiative (Dutch Heart Foundation, Dutch Federation of University Medical Centers, Netherlands Organization for Health Research and Development, and Royal Netherlands Academy of Sciences) grants CVON‐2017‐15 RESCUED (H.L.T.) and CVON‐2018‐30 Predict‐2 (M.T.B., H.L.T.). The Arrest registry is supported by an unconditional grant of Stryker Emergency Care, Redmond, WA, USA. The Danish Cardiac Arrest Registry was supported by Trygfonden. The funders were not involved in designing the study, collecting and analysing the data, preparing the manuscript, or decision to publish. Publisher Copyright: © 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

PY - 2022

Y1 - 2022

N2 - Aims: Opioid use has substantially increased in the last decade and is associated with overdose mortality, but also with increased mortality from cardiovascular causes. This finding may partly reflect an association between opioids and out-of-hospital cardiac arrest (OHCA). Therefore, we aimed to investigate OHCA-risk of opioids in the community. Methods: We conducted 2 population-based case–control studies separately in the Netherlands (2009–2018) and Denmark (2001–2015). Cases were individuals who experienced OHCA of presumed cardiac cause. Each case was matched with up to 5 non-OHCA-controls according to age, sex and OHCA-date. Conditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: We included 5473 OHCA-cases matched with 21 866 non-OHCA-controls in the Netherlands, and 35 017 OHCA-cases matched with 175 085 non-OHCA-controls in Denmark. We found that use of opioids (the Netherlands: cases: 5.4%, controls: 1.8%; Denmark: cases: 11.9%, controls: 4.4%) was associated with increased OHCA-risk in both regions (the Netherlands: OR 2.1 [95% CI 1.8–2.5]; Denmark: OR 1.8 [95% CI 1.5–2.1]). The association was observed in both sexes, and in individuals with cardiovascular disease (the Netherlands: OR 1.8 [95% CI 1.5–2.1]; Denmark: OR 1.6 [95% CI 1.5–1.7]) or without (the Netherlands: OR 3.4 [95% CI: 2.4–4.8], Pinteraction <.0001; Denmark: OR 2.3 [95% CI: 2.0–2.5], Pinteraction <.0001). Conclusion: Use of opioids is associated with increased OHCA-risk in both sexes, independently of concomitant cardiovascular disease. These findings should be considered when evaluating the harms and benefits of treatment with opioids.

AB - Aims: Opioid use has substantially increased in the last decade and is associated with overdose mortality, but also with increased mortality from cardiovascular causes. This finding may partly reflect an association between opioids and out-of-hospital cardiac arrest (OHCA). Therefore, we aimed to investigate OHCA-risk of opioids in the community. Methods: We conducted 2 population-based case–control studies separately in the Netherlands (2009–2018) and Denmark (2001–2015). Cases were individuals who experienced OHCA of presumed cardiac cause. Each case was matched with up to 5 non-OHCA-controls according to age, sex and OHCA-date. Conditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: We included 5473 OHCA-cases matched with 21 866 non-OHCA-controls in the Netherlands, and 35 017 OHCA-cases matched with 175 085 non-OHCA-controls in Denmark. We found that use of opioids (the Netherlands: cases: 5.4%, controls: 1.8%; Denmark: cases: 11.9%, controls: 4.4%) was associated with increased OHCA-risk in both regions (the Netherlands: OR 2.1 [95% CI 1.8–2.5]; Denmark: OR 1.8 [95% CI 1.5–2.1]). The association was observed in both sexes, and in individuals with cardiovascular disease (the Netherlands: OR 1.8 [95% CI 1.5–2.1]; Denmark: OR 1.6 [95% CI 1.5–1.7]) or without (the Netherlands: OR 3.4 [95% CI: 2.4–4.8], Pinteraction <.0001; Denmark: OR 2.3 [95% CI: 2.0–2.5], Pinteraction <.0001). Conclusion: Use of opioids is associated with increased OHCA-risk in both sexes, independently of concomitant cardiovascular disease. These findings should be considered when evaluating the harms and benefits of treatment with opioids.

KW - epidemiology

KW - opioids

KW - sudden cardiac arrest

U2 - 10.1111/bcp.15157

DO - 10.1111/bcp.15157

M3 - Journal article

C2 - 34837236

AN - SCOPUS:85121729810

VL - 88

SP - 2256

EP - 2266

JO - British Journal of Clinical Pharmacology, Supplement

JF - British Journal of Clinical Pharmacology, Supplement

SN - 0264-3774

IS - 5

ER -