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. We assessed the effects of undifferentiated lipid-lowering pretrea...

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Main Authors: 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.
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Published: Karger Publishers 2018
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Online Access:https://eprints.nottingham.ac.uk/51567/
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author 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.
author_facet 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.
author_sort Minhas, Jatinder S.
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-515672020-05-04T19:34:02Z https://eprints.nottingham.ac.uk/51567/ 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. 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. Karger Publishers 2018-04-27 Article PeerReviewed 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. and Robinson, Thompson G. (2018) 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). pp. 213-220. ISSN 1421-9786 Lipid-lowering therapy; Statins; Stroke; Intracranial haemorrhage; Risk factors; Acute stroke outcome https://www.karger.com/Article/Abstract/488911 doi:10.1159/000488911 doi:10.1159/000488911
spellingShingle Lipid-lowering therapy; Statins; Stroke; Intracranial haemorrhage; Risk factors; Acute stroke outcome
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.
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Lipid-lowering therapy; Statins; Stroke; Intracranial haemorrhage; Risk factors; Acute stroke outcome
url https://eprints.nottingham.ac.uk/51567/
https://eprints.nottingham.ac.uk/51567/
https://eprints.nottingham.ac.uk/51567/