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.

ImportanceSurvivors of spontaneous (ie, nontraumatic and with no known structural cause) intracerebral hemorrhage (ICH) have an increased risk of major cardiovascular events (MACEs), including recurrent ICH, ischemic stroke (IS), and myocardial infarction (MI). Only limited data are available from large, unselected population studies assessing the risk of MACEs according to index hematoma location.ObjectiveTo examine the risk of MACEs (ie, the composite of ICH, IS, spontaneous intracranial extra-axial hemorrhage, MI, systemic embolism, or vascular death) after ICH based on ICH location (lobar vs nonlobar).Design, Setting, and ParticipantsThis cohort study identified 2819 patients in southern Denmark (population of 1.2 million) 50 years or older hospitalized with first-ever spontaneous ICH from January 1, 2009, to December 31, 2018. Intracerebral hemorrhage was categorized as lobar or nonlobar, and the cohorts were linked to registry data until the end of 2018 to identify the occurrence of MACEs and separately recurrent ICH, IS, and MI. Outcome events were validated using medical records. Associations were adjusted for potential confounders using inverse probability weighting.ExposureLocation of ICH (lobar vs nonlobar).Main Outcomes and MeasuresThe main outcomes were MACEs and separately recurrent ICH, IS, and MI. Crude absolute event rates per 100 person-years and adjusted hazard ratios (aHRs) with 95% CIs were calculated. Data were analyzed from February to September 2022.ResultsCompared with patients with nonlobar ICH (n = 1255; 680 [54.2%] men and 575 [45.8%] women; mean [SD] age, 73.5 [11.4] years), those with lobar ICH (n = 1034; 495 [47.9%] men and 539 [52.1%] women, mean [SD] age, 75.2 [10.7] years) had higher rates of MACEs per 100 person-years (10.84 [95% CI, 9.51-12.37] vs 7.91 [95% CI, 6.93-9.03]; aHR, 1.26; 95% CI, 1.10-1.44) and recurrent ICH (3.74 [95% CI, 3.01-4.66] vs 1.24 [95% CI, 0.89-1.73]; aHR, 2.63; 95% CI, 1.97-3.49) but not IS (1.45 [95% CI, 1.02-2.06] vs 1.77 [95% CI, 1.34-2.34]; aHR, 0.81; 95% CI, 0.60-1.10) or MI (0.42 [95% CI, 0.22-0.81] vs 0.64 [95% CI, 0.40-1.01]; aHR, 0.64; 95% CI, 0.38-1.09).Conclusions and RelevanceIn this cohort study, spontaneous lobar ICH was associated with a higher rate of subsequent MACEs than nonlobar ICH, primarily due to a higher rate of recurrent ICH. This study highlights the importance of secondary ICH prevention strategies in patients with lobar ICH.

Purpose: Danish registries could be an attractive resource for studies of recurrent intracerebral hemorrhage (re-ICH). We developed and validated algorithms to identify re-ICH in the Danish Stroke Registry (DSR) and the Danish National Patient Registry (DNPR). Patients and Methods: Using multiple sources, we followed-up an inception cohort with verified first-ever spontaneous ICH (n = 2528) for their first re-ICH in 2009-2018 (study period). We used verified cases of re-ICH (n = 124) as the gold standard to assess the performance of register-based algorithms for identifying re-ICH. For each cohort member, we traced events of re-ICH (ICD-10-code I61) in the study period according to DSR and DNPR, respectively. For each registry, we tested algorithms with a blanking period (BP) -ie, a period immediately following the index ICH during which outcome events were ignoredof varying length (7 days-360 days). The algorithm with the shortest BP that returned a positive predictive value (PPV) of ≥80% was considered optimal. We also calculated negative predictive value (NPV), sensitivity, and specificity of each algorithm and [95% confidence intervals] for all proportions. Results: The optimal algorithm for DSR (BP 30 days) had a PPV of 89.