Mortality and Causes of Death among Individuals in a National Opioid Agonist Treatment Cohort

Introduction: People with opioid use disorder experience markedly elevated all-cause and cause-specific mortality. Opioid-agonist treatment (OAT) reduces mortality risk, and OAT populations across Europe are ageing, with cardiovascular, respiratory, and liver diseases accounting for a growing proportion of deaths. However, cause-specific mortality beyond overdose remains poorly characterized in large national cohorts. Methods: We conducted a retrospective cohort study including all 26,031 individuals (76% men) recorded in the Austrian national OAT registry between January 1, 2002, and December 31, 2019, linked to the national causes of death registry with follow-up through December 31, 2021. We calculated sex-specific age-standardized mortality rates per 100,000 person-years (2013 European Standard Population), standardized rate ratios (SRRs), and cause-specific standardized mortality ratios (SMRs) compared with the Austrian general population. Results: Across 278,959 person-years of follow-up, 2,358 deaths occurred. Cohort members had substantially higher mortality across all causes, with greater excess among women (SRR 7.06, 95% CI 6.45-7.72) than men (3.86; 3.69-4.04). Beyond substance use-related causes (SMR 33.2, 95% CI 31.4-35.2), the highest SMRs were found for viral hepatitis (63.8, 52.3-77.8), HIV (48.6, 39.0-60.6), and valvular heart diseases and endocarditis (28.4, 18.6-43.6). By the early to mid-40s, deaths from non-communicable diseases collectively exceeded those from substance use-related causes. Conclusion: Austria´s national OAT cohort experiences substantial excess mortality across all major causes, with high relative excess for substance use-related, infectious, and liver-related conditions. As OAT populations age, non-communicable diseases account for an increasing share of deaths. Future analyses linking the cohort to additional data sources will be needed to disentangle the underlying contributions to this excess mortality.