Randomized Controlled Trial of Early Versus Delayed Statin Therapy in Patients With Acute Ischemic Stroke

See related article, p 2922 To improve survival and ameliorate disability after ischemic stroke, many treatment modalities have been used in the acute stage of stroke. Among them, intravenous tPA (tissue-type plasminogen activator) therapy and immediate endovascular thrombectomy have improved clinical outcomes, especially in patients with severe acute ischemic stroke. Several observational studies showed that the administration of statins before ischemic stroke onset was associated with less physical disability and that statin administration during hospitalization was associated with better survival and disability outcomes. However, 1 small randomized controlled trial (RCT) failed to show the benefit of statin use at the acute phase of ischemic stroke for significantly decreased disability. A recent meta-analysis proposed the necessity of an RCT to determine the usefulness of statin therapy for acute ischemic stroke. Thus, we conducted a multicenter RCT to determine the relative efficacy of early versus delayed statin treatment in patients with acute ischemic stroke. We hypothesized that early statin treatment would be associated with significantly improved physical disability at 90 days after acute ischemic stroke. Background and Purpose—Several studies suggested that statins during hospitalization were associated with better disability outcomes in patients with acute ischemic stroke, but only 1 small randomized trial is available. Methods—We conducted a multicenter, open-label, randomized controlled trial in patients with acute ischemic strokes in 11 hospitals in Japan. Patients with acute ischemic stroke and dyslipidemia randomly received statins within 24 hours after admission in the early group or on the seventh day in the delayed group, in a 1:1 ratio. Statins were administered for 12 weeks. The primary outcome was patient disability assessed by modified Rankin Scale at 90 days. Results—A total of 257 patients were randomized and analyzed (early 131, delayed 126). At 90 days, modified Rankin Scale score distribution did not differ between groups (P=0.68), and the adjusted common odds ratio of the early statin group was 0.84 (95% confidence interval, 0.53–1.3; P=0.46) compared with the delayed statin group. There were 3 deaths at 90 days (2 in the early group, 1 in the delayed group) because of malignancy. Ischemic stroke recurred in 9 patients (6.9%) in the early group and 5 patients (4.0%) in the delayed group. The safety profile was similar between groups. Conclusions—Our randomized trial involving patients with acute ischemic stroke and dyslipidemia did not show any superiority of early statin therapy within 24 hours of admission compared with delayed statin therapy 7 days after admission to alleviate the degree of disability at 90 days after onset. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT02549846. (Stroke. 2017;48:3057-3063. DOI: 10.1161/STROKEAHA.117.017623.)