Lipid-lowering pretreatment and outcome following intravenous thrombolysis for acute ischaemic stroke: a post hoc analysis of the Enhanced Control Of Hypertension And Thrombolysis Stroke Study trial

Background: Debate exists as to whether statin pretreatment confers an increased risk of 90- day mortality and symptomatic intracranial haemorrhage (sICH) in acute ischaemic stroke (AIS) patients treated with intravenous thrombolysis (IVT). We assessed the effects of undifferentiated lipid-lowering pretreatment on outcomes and interaction with low-dose versus standard-dose alteplase in a post hoc subgroup analysis of ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study). Methods: 3284 thrombolysis-eligible AIS patients (mean age 66.6 years; 38% women), with information on lipid-lowering pretreatment, were randomly assigned to low-dose (0.6mg/kg) or standard-dose (0.9mg/kg) intravenous alteplase within 4.5 hours of symptom onset. 615 (19%) patients received statin or other lipid-lowering pretreatment. The primary clinical outcome was combined endpoint of death or disability (modified Rankin Scale (mRS) scores 2-6) at 90 days. Results: Compared with patients with no lipid-lowering pretreatment, those with lipidlowering pretreatment were significantly older, more likely to be non-Asian and more likely to have a medical history including vascular co-morbidity. After propensity analysis assessment and adjustment for important baseline variables at the time of randomisation, as well as imbalances in management during the first seven days of hospital admission, there were no significant differences in mortality (odds ratio (OR), 0.85; 95% confidence intervals (CI) 0.58-1.25, P=0.42), or in overall 90-day death and disability (OR 0.85, 95%CI 0.67-1.09, P=0.19), despite a significant decrease in sICH among those with lipid lowering pretreatment according to the ECASS-2 definition (OR 0.49, 95%CI 0.28-0.83, P=0.009). No differences in key efficacy or safety outcomes were seen in patients with and without lipid-lowering pretreatment between low- and standard-dose alteplase arms. 5 Conclusions: Lipid-lowering pretreatment is not associated with adverse outcome in AIS patients treated with intravenous alteplase, whether assessed by 90-day death and disability or death alone.