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

Cerebrovasc Dis. 2018;45(5-6):213-220. doi: 10.1159/000488911. Epub 2018 Apr 27.

Abstract

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. 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 the Enhanced Control of Hypertension and Thrombolysis Stroke Study.

Methods: In all, 3,284 thrombolysis-eligible AIS patients (mean age 66.6 years; 38% women), with information on lipid-lowering pretreatment, were randomly assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) intravenous alteplase within 4.5 h of symptom onset. Of the total number of patients, 615 (19%) received statin or other lipid-lowering pretreatment. The primary clinical outcome was combined endpoint of death or disability (modified Rankin Scale scores 2-6) at 90 days.

Results: Compared with patients with no lipid-lowering pretreatment, those with lipid-lowering 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 7 days of hospital admission, there were no significant differences in mortality (OR 0.85; 95% 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 European Co-operative Acute Stroke Study 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.

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.

Keywords: Acute stroke outcome; Intracranial haemorrhage; Lipid-lowering therapy; OR; Risk factors; Statins; Stroke.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Brain Ischemia / blood
  • Brain Ischemia / diagnosis
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / mortality
  • Disability Evaluation
  • Female
  • Fibrinolytic Agents / administration & dosage*
  • Fibrinolytic Agents / adverse effects
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Infusions, Intravenous
  • Intracranial Hemorrhages / chemically induced
  • Lipids / blood*
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Factors
  • Stroke / blood
  • Stroke / diagnosis
  • Stroke / drug therapy*
  • Stroke / mortality
  • Thrombolytic Therapy / adverse effects
  • Thrombolytic Therapy / methods*
  • Thrombolytic Therapy / mortality
  • Time Factors
  • Tissue Plasminogen Activator / administration & dosage*
  • Tissue Plasminogen Activator / adverse effects
  • Treatment Outcome

Substances

  • Biomarkers
  • Fibrinolytic Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipids
  • Tissue Plasminogen Activator