Abstract

Survivors of spontaneous intracerebral hemorrhage (ICH) may have indications for statin therapy. The effect of statins on the risk of subsequent hemorrhagic and ischemic stroke (IS) in this setting is uncertain. We sought to determine the risk of any stroke (ischemic stroke, IS or recurrent-ICH), IS and recurrent-ICH associated with statin use among ICH-survivors. Using the Danish Stroke Registry, we identified all patients admitted to a hospital in Denmark (population 5.8 million) with a first-ever ICH between January 2003-to-December 2021 who were age ≥50-years and survived >30-days. Patients were followed until August 2022. Within this cohort, we conducted three nested case-control analyses for any stroke, IS, and recurrent-ICH. We matched controls for age, sex, time since first-ever ICH, and history of prior IS. The primary exposure was statin use before or on the date of subsequent stroke or the equivalent date in matched controls. Using conditional logistic regression, we calculated adjusted odds ratios (aORs) and corresponding 95% confidence intervals (CIs) for any stroke, IS, and recurrent-ICH associated with statin exposure. We identified 1,959 patients with any stroke (women 45.3%; mean [SD] age, 72.6 [9.7] years) who were matched to 7,400 controls; 1,073 patients with IS (women 42.0%; mean [SD] age, 72.4 [10.0] years) who were matched to 4,035 controls, and 984 patients with recurrent-ICH (women 48.7%; mean [SD] age, 72.7 [9.2] years) who were matched to 3,755 controls. Statin exposure was associated with a lower risk of both any stroke (cases 38.6%, controls 41.1%; (aOR 0.88; 95%CI, 0.78-0.99) and IS (cases 39.8%, controls 41.8%, aOR 0.79; 95%CI, 0.67-0.92), but was not associated with recurrent-ICH risk (cases 39.1%, controls 40.8%, aOR 1.05; 95%CI, 0.88-1.24). Exposure to statins was not associated with an increased risk of recurrent-ICH but was associated with lower risk of any stroke, largely due to a lower risk of IS. Confirmation of these findings in randomized trials is needed. This study provides class III evidence that statin use in ICH patients is associated with a lower risk of any stroke and IS and not with increased risk of recurrent-ICH.

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