Department of Cardiology, Heart Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Br J Clin Pharmacol. 2022 May;88(5):2256-2266. doi: 10.1111/bcp.15157. Epub 2021 Dec 23.
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.
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).
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], P < .0001; Denmark: OR 2.3 [95% CI: 2.0-2.5], P < .0001).
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.
在过去十年中，阿片类药物的使用大幅增加，与过量死亡相关，但也与心血管原因导致的死亡率增加相关。这一发现可能部分反映了阿片类药物与院外心脏骤停（OHCA）之间的关联。因此，我们旨在研究社区中阿片类药物与 OHCA 的风险。
我们分别在荷兰（2009-2018 年）和丹麦（2001-2015 年）进行了两项基于人群的病例对照研究。病例为疑似心源性 OHCA 的个体。每个病例都根据年龄、性别和 OHCA 日期与多达 5 名非 OHCA 对照相匹配。使用条件逻辑回归分析计算比值比（OR）和 95%置信区间（CI）。
我们纳入了荷兰的 5473 例 OHCA 病例和 21866 例非 OHCA 对照，以及丹麦的 35017 例 OHCA 病例和 175085 例非 OHCA 对照。我们发现，在两个地区，阿片类药物的使用（荷兰：病例：5.4%，对照：1.8%；丹麦：病例：11.9%，对照：4.4%）与 OHCA 风险增加相关（荷兰：OR 2.1 [95% CI 1.8-2.5]；丹麦：OR 1.8 [95% CI 1.5-2.1]）。这种关联在两性中以及患有心血管疾病的个体中（荷兰：OR 1.8 [95% CI 1.5-2.1]；丹麦：OR 1.6 [95% CI 1.5-1.7]）或没有（荷兰：OR 3.4 [95% CI：2.4-4.8]，P ＜0.0001；丹麦：OR 2.3 [95% CI：2.0-2.5]，P ＜0.0001）中均观察到。
无论是否伴有并存的心血管疾病，阿片类药物的使用与两性中 OHCA 风险的增加相关。在评估阿片类药物治疗的危害和益处时，应考虑这些发现。
