Abstract Body (Do not enter title and authors here): Background
Cardiac arrest frequently co-occurs with substance use disorders, yet national trends and disparities in this population remain underexplored.

Hypothesis
We hypothesized that age adjusted mortality rates (AAMR) for cardiac arrest in adults ≥25 years with substance use disorders increased over time and that significant disparities exist by sex, race/ethnicity, geography, and urban/rural status.

Methods
We analyzed CDC WONDER multiple cause-of-death data (1999–2024) for U.S. decedents aged ≥25 years with cardiac arrest (ICD-10 I46) and substance use disorders (ICD-10 F10–F19). We calculated total deaths, place-of-death proportions (medical facility, home, nursing home/long-term care, hospice, and others); annual AAMRs per 100,000; and Joinpoint regression–derived average annual percent change (AAPC) in AAMR. Analyses were stratified by sex, race/ethnicity (NH White, NH Black, Hispanic, NH Other), Census region (Northeast, Midwest, South, West), and urban versus rural status (data available 1999-2020).

Results
From 1999 to 2024, 710,933 adults ≥ 25 years died from cardiac arrest with substance use disorders (456,758 men; 254,175 women). Medical facilities accounted for 55.3% of deaths, followed by home (31.2%), nursing home/long-term care (6.8%), hospice (2.4%), and other locations (4.3%). Overall AAMR rose from 2.6 to 13.7 per 100,000; Joinpoint analysis showed AAPCs of +27.6% (1999–2005), +4.9% (2005–2013), +2.2% (2013–2021), and –6.8% (2021–2024) (all p < 0.001). In 2020, men’s AAMR peaked at 23.5 versus 10.7 for women. NH Black individuals had the highest AAMR (13.2), followed by NH White (12.3) and Hispanic (6.3); NH Black individuals experienced an APC of +35.8% from 2002 to 2005 (p < 0.05). The Northeast had the highest average AAMR (17.1) versus the West (9.2). In 2020, rural AAMR (14.6) exceeded urban (10.6). State AAMRs ranged from 3.8 (Maryland) to 27.7 (New York). Decedents were 80.6% NH White, 11.7% NH Black, 4.9% Hispanic, and 2.4% NH Other.

Conclusions
Cardiac arrest mortality among U.S. adults with substance use disorders surged from 1999 through 2021 before declining through 2024. Persistent disparities by sex, race/ethnicity, region, and urban/rural status underscore the need for targeted interventions addressing substance use and cardiac arrest prevention in high-risk groups.