Functional disability after clinically significant extracranial bleeding: a secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) Trial

Background: Clinically significant extracranial bleeding, defined as bleeding at any site other than the brain or spinal cord requiring either a hospital admission >24 hours, red blood cell transfusion, surgery for hemostasis, or resulting in death, is a common side effect of antithrombotic agents. Compared to intracranial bleeding, the impact of clinically significant extracranial bleeding on long-term outcomes, including functional independence, has been poorly studied. Objectives: To determine if clinically significant extracranial bleeding impacts the development of functional disability in healthy older adults. Methods: We performed a secondary analysis of the Aspirin in Reducing Events in the Elderly trial. The primary outcome of this study was incident dependence in the Katz Activities of Daily Living (ADLs), defined as being unable to perform or requiring assistance with any ADLs or being admitted to a long-term care facility. Results: A total of 18 982 participants were included in the analysis, of which 547 (2.9%) developed clinically significant extracranial bleeding during study follow-up. In adjusted analyses, clinically significant extracranial bleeding was significantly associated with the development of incident ADL dependence (hazard ratio [HR], 2.46; 95% CI, 1.97-3.07). This finding was similar for gastrointestinal (HR, 2.29; 95% CI, 1.72-2.08) and nongastrointestinal extracranial bleeds (HR, 2.68; 95% CI, 1.96-3.69). The association with increased risk of incident ADL dependence remained significant in secondary analysis of groups randomized to either aspirin (HR, 2.15; 95% CI, 1.57-2.94) or placebo (HR, 2.84; 95% CI, 2.09-3.86). Conclusion: Clinically significant extracranial bleeding was associated with the development of incident ADL dependence in otherwise healthy older adults.