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Drug Safety
Published in: Drug Safety 6/2017

01-06-2017 | Original Research Article

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

Authors: Kathrin Jobski, Bianca Kollhorst, Edeltraut Garbe, Tania Schink

Published in: Drug Safety | Issue 6/2017

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Abstract

Introduction

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.

Objectives

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.

Methods

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.

Results

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).

Conclusions

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.
Appendix
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Metadata
Title
The Risk of Ischemic Cardio- and Cerebrovascular Events Associated with Oxycodone–Naloxone and Other Extended-Release High-Potency Opioids: A Nested Case–Control Study
Authors
Kathrin Jobski
Bianca Kollhorst
Edeltraut Garbe
Tania Schink
Publication date
01-06-2017
Publisher
Springer International Publishing
Published in
Drug Safety / Issue 6/2017
Print ISSN: 0114-5916
Electronic ISSN: 1179-1942
DOI
https://doi.org/10.1007/s40264-017-0511-8

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