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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.

Authors

Jatinder S. Minhas

Xia Wang

Hisatomi Arima

PHILIP BATH philip.bath@nottingham.ac.uk
Stroke Association Professor of Stroke Medicine

Laurent Billot

Joseph P. Broderick

Geoffrey A. Donnan

Jong S. Kim

Pablo M. Lavados

Tsong-Hai Lee

Sheila Cristina Ouriques Martins

Verónica V. Olavarría

Jeyaraj D. Pandian

Octávio Marques Pontes-Neto

Stefano Ricci

Shoichiro Sato

Vijay K. Sharma

Nguyen H. Thang

Ji-Guang Wang

Mark Woodward

John Chalmers

Craig S. Anderson

Thompson G. Robinson



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 http://eprints.nottingham.ac.uk/id/eprint/51567
Publisher URL https://www.karger.com/Article/Abstract/488911
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf
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

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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