Aplastic anemia and substance use: National trends and associations in the United States from 1999-2023- a CDC wonder analysis

Abstract Background: In recent years, aplastic anemia has emerged as a life-threatening disease, with known links to certain medications and toxins. However, links between substance use and aplastic anemia have been underexplored. This study examines trends and disparities in mortality related to substance use-associated aplastic anemia among adults in the United States. Methods: Data was analyzed from the CDC WONDER database to observe mortality and identify trends in aplastic anemic patients with substance use aged ≥25 years from 1999-2023. Age-adjusted mortality rates (AAMRs) and crude mortality rates (CMRs) per 100,000 persons, average annual percent change (AAPC), and annual percent change (APC) with their 95% CI were calculated and categorized by sex, year, race, geographic location, and age. Joinpoint Regression Program (V 5.4.0, National Cancer Institute) was used to quantify these trends. Results: From 1999-2023, a total of 117,737 deaths related to substance use in aplastic anemic patients were recorded. AAMR demonstrated an overall significant incline, from 0.39 in 1999 to 3.15 in 2023 (AAPC: 9.91; 95% CI: 8.57-11.25; p 0.0000001). Men observed a higher overall AAMR as compared to women (2.72 vs 1.43), consequently experiencing a higher number of deaths (70,240 vs 47,497). The majority of deaths were demonstrated by NH White individuals (100,921), however NH Black/African American individuals demonstrated a greater overall AAMR as compared to NH White (2.35 vs 1.99). When stratified by geographic location, the highest overall AAMR was exhibited by the Midwest (2.49), followed by the South (2.05), the Northeast (1.79), and the West (1.47). From 1999-2020, non-metropolitan areas observed a higher overall AAMR as compared to metropolitan areas (2.54 vs 1.64), while also exhibiting a greater AAPC of 11.94 (95% CI: 10.30-13.60; p 0.000001), however, mortality was higher in metropolitan areas (68.571 vs 22,119 deaths). Between 1999 and 2023, AAMR ranged from 0.56 in California, to 8.35 in Minnesota. States that consistently classified in the top 90th percentile were Nebraska, North Dakota, Oregon, South Dakota, and Wyoming, which had roughly double the AAMRs as compared to states that classified in the lower 10th percentile. Older adults saw a higher overall CMR of 7.38 as compared to middle-aged adults (1.38), and young adults (0.13). Conclusion: Throughout the study period, the toll on substance use in patients with aplastic anemia observed a marked rise. Men and African American individuals experienced disproportionately higher mortality rates, while NH White individuals accounted for a higher mortality. Although mortality rates were highest among older adults, a consistent rise across all age groups raises public health concerns. These findings indicate that preventive measures must be taken to improve hematologic care.