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

Talip E Eroglu, Carlo A Barcella, Marieke T Blom, Patrick C Souverein, Grimur H Mohr, Christian Torp-Pedersen, Fredrik Folke, Mads Wissenberg, Anthonius de Boer, Gunnar H Gislason, Hanno L Tan*, ESCAPE-NET Investigators

*Corresponding author for this work


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.

Original languageEnglish
JournalBritish Journal of Clinical Pharmacology
Issue number5
Pages (from-to)2256-2266
Number of pages11
Publication statusPublished - May 2022


  • Analgesics, Opioid/adverse effects
  • Case-Control Studies
  • Drug Overdose/complications
  • Female
  • Humans
  • Male
  • Opioid-Related Disorders/complications
  • Out-of-Hospital Cardiac Arrest/chemically induced
  • Registries
  • epidemiology
  • sudden cardiac arrest
  • opioids


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