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

Minhas, Jatinder S.; Wang, Xia; Arima, Hisatomi; Bath, Philip M.W.; Billot, Laurent; Broderick, Joseph P.; Donnan, Geoffrey A.; Kim, Jong S.; Lavados, Pablo M.; Lee, Tsong-Hai; Martins, Sheila Cristina Ouriques; Olavarría, Verónica V.; Pandian, Jeyaraj D.; Pontes-Neto, Octávio Marques; Ricci, Stefano; Sato, Shoichiro; Sharma, Vijay K.; Thang, Nguyen H.; Wang, Ji-Guang; Woodward, Mark; Chalmers, John; Anderson, Craig S.; Robinson, Thompson G.

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.

Citation

Minhas, J. S., Wang, X., Arima, H., Bath, P. M., Billot, L., Broderick, J. P., …Robinson, T. G. (in press). 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. Cerebrovascular Diseases, 45(5-6), https://doi.org/10.1159/000488911

• Journal Article Type: Article
• Acceptance Date: Mar 3, 2018
• Online Publication Date: Apr 27, 2018
• Deposit Date: May 4, 2018
• Publicly Available Date: May 4, 2018
• Journal: Cerebrovascular Diseases
• Print ISSN: 1015-9770
• Electronic ISSN: 1421-9786
• Publisher: Karger Publishers
• Peer Reviewed: Peer Reviewed
• Volume: 45
• Issue: 5-6
• DOI: https://doi.org/10.1159/000488911
• Keywords: Lipid-lowering therapy; Statins; Stroke; Intracranial haemorrhage; Risk factors; Acute stroke outcome
• Public URL: https://nottingham-repository.worktribe.com/output/929176
• Publisher URL: https://www.karger.com/Article/Abstract/488911
• Additional Information: This is the peer-reviewed but unedited manuscript version of the following article: Minhas J, S, Wang X, Arima H, Bath P, M, Billot L, Broderick J, P, Donnan G, A, Kim J, S, Lavados P, M, Lee T, -H, Martins S, C, O, Olavarría V, V, Pandian J, D, Pontes-Neto O, M, Ricci S, Sato S, Sharma V, K, Thang N, H, Wang J, -G, Woodward M, Chalmers J, Anderson C, S, Robinson T, G, 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; 45:213-220. The final, published version is available at http://www.karger.com/?doi=/10.1159/000488911