Older adults are the most rapidly increasing age group globally. 1 55% to 95% of older adults are categorized as multimorbid, and the prevalence is increasing with age. 2 Thus, older adults tend to receive more medical treatment compared to younger people. 3 Treatment guidelines are primarily based on data from randomized clinical trials (RCTs) 4 that tend to some extent to exclude older adults. The insufficient inclusion of older adults is reflected by a lower external validity in RCTs, where the average age, level of function, comorbidities and number of prescribed drugs do not reflect the target population. 5 Using data from RCTs not including older adults sufficiently is problematic since the age-related physiological changes are not taken into account. 6 For instance,

Background:A causal relationship between statin use and intracerebral hemorrhage (ICH) is uncertain. We hypothesized that an association between long-term statin exposure and ICH risk might vary for different ICH locations.Methods:We conducted this analysis using linked Danish nationwide registries. Within the Southern Denmark Region (population 1.2 million), we identified all first-ever cases of ICH between 2009-2018 in persons ages>55 years. Patients with medical record verified diagnoses were classified as having a lobar or non-lobar ICH and matched for age, sex, and calendar year to general population controls. We used a nationwide prescription registry to ascertain prior statin and other medication use that we classified for recency, duration, and intensity. Using conditional logistic regression adjusted for potential confounders, we calculated adjusted odds ratios (aORs) and corresponding 95% Confidence Intervals (CIs) for the risk of lobar and non-lobar ICH.Results:We identified 989 patients with lobar ICH (52.2% women, mean age 76.3-years) who we matched to 39,500 controls, and 1,175 patients with non-lobar ICH (46.5% women, mean age 75.1-years) who we matched to 46,755 controls. Current statin use was associated with a lower risk of lobar (aOR 0.83; 95%CI, 0.70-0.98) and non-lobar ICH (aOR 0.84; 95%CI, 0.72-0.98). Longer duration of statin use was also associated with lower risk of lobar (<1 year: aOR 0.89; 95%CI, 0.69-1.14; ≥1 year to <5years aOR 0.89; 95%CI 0.73-1.09; ≥5 years aOR 0.67; 95%CI, 0.51-0.87;pfor trend 0.040) and non-lobar ICH (<1 year: aOR1.00; 95%CI, 0.80-1.25; ≥1 year to <5years aOR 0.88; 95%CI 0.73-1.06; ≥5 years aOR 0.62; 95%CI, 0.48-0.80;pfor trend <0.001). Estimates stratified by statin intensity were similar to the main estimates for low-medium intensity therapy (lobar aOR 0.82; non-lobar aOR 0.84); the association with high intensity therapy was neutral.Discussion:We found that statin use was associated with a lower risk of ICH, particularly with longer treatment duration. This association did not vary by hematoma location.