Dose-Related Effects of Statins on Symptomatic Intracerebral Hemorrhage and Outcome After Thrombolysis for Ischemic Stroke

Abstract

H MG-CoA reductase inhibitors (ie, statins) constitute a cornerstone in primary and secondary prevention of ischemic stroke.1 In addition to dose-dependent cholesterol-lowering effects, statins have dose-dependent pleiotropic effects, including antithrombotic properties, and were shown to modify fibrinolytic balance toward a more profibrinolytic state.2 These properties may contribute to the beneficial impact of statins on outcome after ischemic stroke, which was recently confirmed in a large meta-analysis. 3 However, studies on patients receiving intravenous thrombolysis (IVT) reported conflicting results, and the effects on outcome seemed to be attenuated. [3][4][5] Rather, there has been a discussion that patients with previous statin use might be more likely to develop symptomatic intracerebral hemorrhage (sICH) after IVT. [5][6][7] A recently published meta-analysis showed a positive association of statins with IVT-related sICH, but the statistical significance was lost if only studies with adjusted analyses were included. 5Previous studies investigating the impact of statins on outcome and sICH after IVT lacked information about statin dose. Using pooled data from 2 large European thrombolysis registries, we aimed to analyze the effects of statin dose on risk of sICH and outcome after IVT.Background and Purpose-The aim of our study was to assess whether statins have dose-dependent effects on risk of symptomatic intracerebral hemorrhage (sICH) and outcome after intravenous thrombolysis for ischemic stroke. Methods-We pooled data from 2 European intravenous thrombolysis registries. Statin doses were stratified in 3 groups according to the attainable lowering of cholesterol levels (low dose: simvastatin 20 mg or equivalent; medium dose: simvastatin 40 mg or equivalent; and high dose: simvastatin 80 mg or equivalent). sICH was defined according to the European Cooperative Acute Stroke Study. Modified Rankin Scale score 0 to 2 at 3 months was considered a favorable outcome. Results-Among 1446 patients analyzed (median age, 75 years; median initial National Institutes of Health Stroke Scale score, 11; 54% men), 317 (22%) used statins before intravenous thrombolysis. Of them, 120 patients had low-dose, 134 medium-dose, and 63 high-dose statin therapy. sICH occurred in 4% of patients (n=53). Frequency of sICH was 2%, 6%, and 13% in patients with low-, medium-, and high-dose statin treatment, respectively (P<0.01). Adjusted odds ratio (OR) for sICH was 2. 4,9,10 All patients were treated in a specialized stroke unit for ≥24 hours. The registries were approved by the respective ethics committees.Baseline characteristics, including age, sex, and medical history (atrial fibrillation, coronary artery disease, current smoking, diabetes mellitus, hypertension, and previous stroke), were collected. Stroke severity was assessed via the National Institutes of Health Stroke Scale (NIHSS) by certified raters. Moreover, onsetto-treatment time and blood pressure on admission were recorded. Laboratory measures included glucose l...

Intravenous Thrombolysis in Patients Dependent on the Daily Help of Others Before Stroke

“…[6][7][8][9] Local study investigators filled in the forms systematically using prospectively ascertained in-hospital intravenous ischemic stroke thrombolysis registries. Completed forms from all centers were compiled in the coordinating center Basel, where the analysis of the pooled data was performed, as done previously.…”

Number of Cerebral Microbleeds and Risk of Intracerebral Hemorrhage After Intravenous Thrombolysis

“…This is in line with recent observations that especially patients using higher statin doses might be prone to hemorrhagic complications. 30 Moreover, higher blood pressure on admission was confirmed to be associated with thrombolysis-related ICH. 31 In univariate analysis, patients with presence of ≥5 CMBs were less likely to achieve a favorable outcome, but in multivariable analysis, the association did not remain significant.…”

Recanalization Therapies in Acute Ischemic Stroke Patients

“…[27][28][29] Local investigators completed the forms systematically using data from (1) prospectively ascertained in-hospital thrombolysis or stroke registries or (2) from patients' records and charts in case patients were identified by local patient lists about consecutive IVT/IAT. Completed forms from all centers were sent to the coordinating center in Basel, where analyses of pooled data were performed.…”

“…Variables likely to affect outcome or complications were chosen based on previous studies. [27][28][29][30] PSM predictors were age, sex, time-to-treatment, admission NIHSS, systolic and diastolic blood pressure, blood glucose level, creatinine and prior medication with statins, antihypertensive agents, or antiplatelets, as well, and the presence of diabetes mellitus, hypertension, hypercholesterolemia, coronary artery disease, atrial fibrillation, and history of previous ischemic stroke.…”