Gender differences in association of prescription opioid use and mortality: A propensity-matched analysis from the REasons for Geographic And Racial Differences in Stroke (REGARDS) prospective cohort

Abstract

Background

Prescription opioids (PO) have been widely used for chronic non-cancer pain, with commensurate concerns for overdose. The long-term effect of these medications on non-overdose mortality in the general population remains poorly understood. This study’s objective was to examine the association of prescription opioid use and mortality in a large cohort, accounting for gender differences and concurrent benzodiazepine use, and using propensity score matching. Methods: 29,025 US community-dwellers were enrolled in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort between 2003 and 2007, and followed through December 31, 2012. At baseline there were 1907 participants with PO; 1864 of them were matched to participants without PO, based on the model-derived propensity to receive opioid prescriptions. Causes of death were expert-adjudicated. Results: Over median follow-up of 6 years there were 4428 deaths (413 among persons with PO). The risk for all-cause mortality was 12% higher, in absolute terms, for persons with PO compared to those without PO in the overall sample, with gender differences (interaction p = .0008). The risk of death was increased for women with PO (hazard ratio [HR] 1.21 [95% Confidence Interval (CI) 1.04–1.40]), but not men (HR 0.92 [95% CI 0.77–1.10]). Women with PO were at higher risk of cardiovascular disease (CVD) death (HR 1.43 [95% CI 1.12–1.84]), sudden death (HR 2.02 [95% CI 1.29–3.15]) (a subset of CVD death), and accidents (HR 2.18 [95% CI 1.03–4.60]). These risks were not observed for men with PO. Conclusion: Over 6 years of follow-up, women but not men who had opioid prescriptions were at higher risk of all-cause mortality, CVD death, sudden death, and accidents. Special caution in prescribing opioids for women may be warranted until these findings are confirmed.

Keywords:

• Prescription opioids; mortality; cohort study; propensity score

Disclosure statement

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke or the National Institutes of Health. The authors thank the other investigators, the staff, and the participants of the REGARDS study for their valuable contributions. A full list of participating REGARDS investigators and institutions can be found at http://www.regardsstudy.org The REGARDS study invites collaboration. More information can be found on the REGARDS web-site: http://www.regardsstudy.org/researchers.

Author contributions

Drs. Monika Safford and Yulia Khodneva had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. YK has developed the concept of the study, performed statistical analysis and drafted the text of the manuscript, figures and tables. JR performed statistical analysis and reviewed data and manuscript draft. SK assisted in the development of the study concept and reviewed data and manuscript draft. MS has provided overall project supervision, assisted in the development of the study concept and reviewed data and manuscript draft.

Additional information

Funding

This research was supported in part by an Agency for Healthcare Research and Quality (AHRQ) training grant to the University of Alabama at Birmingham (2T32HS013852-16).