Drug Safety

, Volume 40, Issue 6, pp 505–515

The Risk of Ischemic Cardio- and Cerebrovascular Events Associated with Oxycodone–Naloxone and Other Extended-Release High-Potency Opioids: A Nested Case–Control Study

  • Kathrin Jobski
  • Bianca Kollhorst
  • Edeltraut Garbe
  • Tania Schink
Original Research Article

DOI: 10.1007/s40264-017-0511-8

Cite this article as:
Jobski, K., Kollhorst, B., Garbe, E. et al. Drug Saf (2017) 40: 505. doi:10.1007/s40264-017-0511-8



In Germany, an extended-release (ER) combination of the high-potency opioid (HPO) oxycodone and the antagonist naloxone was approved in 2006. In recent years, the cardio- and cerebrovascular safety of opioid antagonists and of opioids themselves has been discussed.


The objective of this study was to estimate the risk of major ischemic cardio- and cerebrovascular events in patients receiving ER oxycodone–naloxone compared with those receiving other ER HPOs.


We used the German Pharmacoepidemiological Research Database (GePaRD) to conduct a nested case–control study (2006–2011) within a cohort of ER HPO users. Cases were defined as patients hospitalized for acute myocardial infarction (MI) or ischemic stroke (IS). For each case, up to ten controls were selected by risk-set sampling. Using conditional logistic regression, confounder-adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were obtained for the risk of MI/IS associated with (1) current HPO treatment, (2) recent discontinuation, or (3) recent switch of HPO therapy compared with past treatment.


In 309,936 ER HPO users, 12,384 MI/IS events were detected, resulting in a crude incidence rate of 19.48 (95% CI 19.14–19.82) per 1000 person years. A small but significantly elevated aOR was found for morphine (1.12; 95% CI 1.04–1.22) but not for oxycodone–naloxone. Recent discontinuation and recent switch of any ER HPO also had a significant impact on the outcome (aOR 1.12; 95% CI 1.04–1.21 and 1.25; 95% CI 1.03–1.52, respectively).


Our study does not indicate an association between oxycodone–naloxone and ischemic cardio- or cerebrovascular events. However, our findings do suggest that every change in ER HPO therapy should be conducted with caution.

Supplementary material

40264_2017_511_MOESM1_ESM.docx (71 kb)
Supplementary material 1 (DOCX 70 kb)

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  1. 1.Leibniz Institute for Prevention Research and Epidemiology-BIPSBremenGermany
  2. 2.Department of Health Services ResearchCarl von Ossietzky University OldenburgOldenburgGermany
  3. 3.Core Scientific Area ‘Health Sciences’University of BremenBremenGermany

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