Published November 26, 2021 | Version v1
Journal article Open

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

  • 1. Department of Cardiology, Heart Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  • 2. Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Gentofte, Denmark
  • 3. Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands

Description

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.

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Additional details

Funding

European Commission
ESCAPE-NET – European Sudden Cardiac Arrest network: towards Prevention, Education and NEw Treatment 733381