High-dose atorvastatin after stroke or transient ischemic attack. Simvastatin in the acute phase of ischemic stroke: a safety and efficacy pilot trial. Fast assessment of stroke and transient ischaemic attack to prevent early recurrence (FASTER): a randomised controlled pilot trial. Aspirin vs anticoagulation in carotid artery dissection: a study of 298 patients.
Statins reduce the incidence of strokes among patients at increased risk for cardiovascular disease; whether they reduce the risk of stroke after a recent stroke or transient ischemic attack (TIA) remains to be established.
                We randomly assigned 4731 patients who had had a stroke or TIA within one to six months before study entry, had low-density lipoprotein (LDL) cholesterol levels of 100 to 190 mg per deciliter (2.6 to 4.9 mmol per liter), and had no known coronary heart disease to double-blind treatment with 80 mg of atorvastatin per day or placebo. The primary end point was a first nonfatal or fatal stroke.
                The mean LDL cholesterol level during the trial was 73 mg per deciliter (1.9 mmol per liter) among patients receiving atorvastatin and 129 mg per deciliter (3.3 mmol per liter) among patients receiving placebo. During a median follow-up of 4.9 years, 265 patients (11.2 percent) receiving atorvastatin and 311 patients (13.1 percent) receiving placebo had a fatal or nonfatal stroke (5-year absolute reduction in risk, 2.2 percent; adjusted hazard ratio, 0.84; 95 percent confidence interval, 0.71 to 0.99; P=0.03; unadjusted P=0.05). The atorvastatin group had 218 ischemic strokes and 55 hemorrhagic strokes, whereas the placebo group had 274 ischemic strokes and 33 hemorrhagic strokes. The five-year absolute reduction in the risk of major cardiovascular events was 3.5 percent (hazard ratio, 0.80; 95 percent confidence interval, 0.69 to 0.92; P=0.002). The overall mortality rate was similar, with 216 deaths in the atorvastatin group and 211 deaths in the placebo group (P=0.98), as were the rates of serious adverse events. Elevated liver enzyme values were more common in patients taking atorvastatin.
                In patients with recent stroke or TIA and without known coronary heart disease, 80 mg of atorvastatin per day reduced the overall incidence of strokes and of cardiovascular events, despite a small increase in the incidence of hemorrhagic stroke. (ClinicalTrials.gov number, NCT00147602 [ClinicalTrials.gov].).
                Copyright 2006 Massachusetts Medical Society. Although statins are being used for secondary prevention of ischemic stroke, recent experimental data have shown new pleiotropic effects of these drugs responsible for their role in neuroprotection. We conducted a pilot, double-blind, randomized, multicenter clinical trial to study for the first time safety and efficacy of simvastatin in the acute phase of ischemic stroke. Simvastatin/placebo was given at 3-12 h from symptom onset to 60 patients with cortical strokes. Efficacy on the evolution of several inflammation markers [interleukin (IL)-6, IL-8, IL-10, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, C-reactive protein, sApo/Fas, tumor necrosis factor-alpha, E-selectin, L-selectin and nitrites+nitrates] and neurological outcome was evaluated at baseline, day 1, 3, 5, 7 and 90. No differences were found amongst the biomarkers studied regarding treatment allocation. Although simvastatin patients improved significantly by the third day (46.4% vs. 17.9%, P = 0.022), a non-significant increase in mortality and greater proportion of infections (odds ratio 2.4, confidence interval 1.06-5.4) in the simvastatin group were the main safety concerns. Therefore, a larger clinical trial is needed to confirm the net benefit of this therapeutic approach. Patients with transient ischaemic attack (TIA) or minor stroke are at high immediate risk of stroke. The optimum early treatment options for these patients are not known.
                Within 24 h of symptom onset, we randomly assigned, in a factorial design, 392 patients with TIA or minor stroke to clopidogrel (300 mg loading dose then 75 mg daily; 198 patients) or placebo (194 patients), and simvastatin (40 mg daily; 199 patients) or placebo (193 patients). All patients were also given aspirin and were followed for 90 days. Descriptive analyses were done by intention to treat. The primary outcome was total stroke (ischaemic and haemorrhagic) within 90 days. Safety outcomes included haemorrhage related to clopidogrel and myositis related to simvastatin. This study is registered as an International Standard Randomised Controlled Trial (number 35624812) and with ClinicalTrials.gov (NCT00109382).
                The median time to stroke outcome was 1 day (range 0-62 days). The trial was stopped early due to a failure to recruit patients at the prespecified minimum enrolment rate because of increased use of statins. 14 (7.1%) patients on clopidogrel had a stroke within 90 days compared with 21 (10.8%) patients on placebo (risk ratio 0.7 [95% CI 0.3-1.2]; absolute risk reduction -3.8% [95% CI -9.4 to 1.9]; p=0.19). 21 (10.6%) patients on simvastatin had a stroke within 90 days compared with 14 (7.3%) patients on placebo (risk ratio 1.3 [0.7-2.4]; absolute risk increase 3.3% [-2.3 to 8.9]; p=0.25). The interaction between clopidogrel and simvastatin was not significant (p=0.64). Two patients on clopidogrel had intracranial haemorrhage compared with none on placebo (absolute risk increase 1.0% [-0.4 to 2.4]; p=0.5). There was no difference between groups for the simvastatin safety outcomes.
                Immediately after TIA or minor stroke, patients are at high risk of stroke, which might be reduced by using clopidogrel in addition to aspirin. The haemorrhagic risks of the combination of aspirin and clopidogrel do not seem to offset this potential benefit. We were unable to provide evidence of benefit of simvastatin in this setting. This aggressive prevention approach merits further study. No randomized study has yet compared efficacy and safety of aspirin and anticoagulants in patients with spontaneous dissection of the cervical carotid artery (sICAD).
                Prospectively collected data from 298 consecutive patients with sICAD (56% men; mean age 46 +/- 10 years) treated with anticoagulants alone (n = 202) or aspirin alone (n = 96) were retrospectively analyzed. Admission diagnosis was ischemic stroke in 165, TIA in 37, retinal ischemia in 8, and local symptoms and signs (headache, neck pain, Horner syndrome, cranial nerve palsy) in 80 patients, while 8 patients were asymptomatic. Clinical follow-up was obtained after 3 months by neurologic examination (97% of patients) or structured telephone interview. Outcome measures were 1) new cerebral ischemic events, defined as ischemic stroke, TIA, or retinal ischemia, 2) symptomatic intracranial hemorrhage, and 3) major extracranial bleeding.
                During follow-up, ischemic events were rare (ischemic stroke, 0.3%; TIA, 3.4%; retinal ischemia, 1%); their frequency did not significantly differ between patients treated with anticoagulants (5.9%) and those treated with aspirin (2.1%). The same was true for hemorrhagic adverse events (anticoagulants, 2%; aspirin, 1%). New ischemic events were significantly more frequent in patients with ischemic events at onset (6.2%) than in patients with local symptoms or asymptomatic patients (1.1%).
                Within the limitations of a nonrandomized study, our data suggest that frequency of new cerebral and retinal ischemic events in patients with spontaneous dissection of the cervical carotid artery is low and probably independent of the type of antithrombotic treatment (aspirin or anticoagulants).
Insufficient data were available from randomized trials to establish if statins are safe and effective in cases of acute ischemic stroke and TIA.