Thrombolysis outcomes according to arterial characteristics of acute ischemic stroke by alteplase dose and blood pressure target

Zien Zhou; Chao Xia; Grant Mair; Candice Delcourt; S. Yoshimura; Xiaosheng Liu; Zengai Chen; A. Malavera; C. Carcel; Xiaoying Chen; Xia Wang; R. Al-Shahi Salman; Thompson G. Robinson; R.I. Lindley; John Chalmers; Joanna M. Wardlaw; Mark W. Parsons; A.M. Demchuk; Craig S. Anderson

doi:10.1177/17474930211025436

Thrombolysis outcomes according to arterial characteristics of acute ischemic stroke by alteplase dose and blood pressure target

Zien Zhou, Chao Xia, Grant Mair, Candice Delcourt, S. Yoshimura, Xiaosheng Liu, Zengai Chen, A. Malavera, C. Carcel, Xiaoying Chen, Xia Wang, R. Al-Shahi Salman, Thompson G. Robinson, R.I. Lindley, John Chalmers, Joanna M. Wardlaw, Mark W. Parsons, A.M. Demchuk, Craig S. Anderson

Research output: Contribution to journal › Article › peer-review

Abstract

Background
We explored the influence of low-dose intravenous alteplase and intensive blood pressure lowering on outcomes of acute ischemic stroke according to status/location of vascular obstruction in participants of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED).
Methods
ENCHANTED was a multicenter, quasi-factorial, randomized trial to determine efficacy and safety of low- versus standard-dose intravenous alteplase and intensive- versus guideline-recommended blood pressure lowering in acute ischemic stroke patients. In those who had baseline computed tomography or magnetic resonance imaging angiography, the degree of vascular occlusion was grouped according to being no (NVO), medium (MVO), or large (LVO). Logistic regression models were used to determine 90-day outcomes (modified Rankin scale [mRS] shift [primary], other mRS cut-scores, intracranial hemorrhage, early neurologic deterioration, and recanalization) by vascular obstruction status/site. Heterogeneity in associations for outcomes across subgroups was estimated by adding an interaction term to the models.
Results
There were 940 participants: 607 in alteplase arm only, 243 in blood pressure arm only, and 90 assigned to both arms. Compared to the NVO group, functional outcome was worse in LVO (mRS shift, adjusted OR [95% CI] 2.13 [1.56–2.90]) but comparable in MVO (1.34 [0.96–1.88]) groups. There were no differences in associations of alteplase dose or blood pressure lowering and outcomes across NVO/MVO/LVO groups (mRS shift: low versus standard alteplase dose 0.84 [0.54–1.30]/0.48 [0.25–0.91]/0.99 [0.75–2.09], Pinteraction = 0.28; intensive versus standard blood pressure lowering 1.32 [0.74–2.38]/0.78 [0.31–1.94]/1.24 [0.64–2.41], Pinteraction = 0.41), except for a borderline significant difference for intensive blood pressure lowering and increased early neurologic deterioration (0.63 [0.14–2.72]/0.17 [0.02–1.47]/2.69 [0.90–8.04], Pinteraction = 0.05).
Conclusions
Functional outcome by dose of alteplase or intensity of blood pressure lowering is not modified by vascular obstruction status/site according to analyses from ENCHANTED, although these results are compromised by low statistical power.

Original language	English
Pages (from-to)	566-575
Number of pages	10
Journal	International Journal of Stroke
Volume	17
Issue number	5
DOIs	https://doi.org/10.1177/17474930211025436
Publication status	Published - Jun 2022
Externally published	Yes

Keywords

Acute ischemic stroke
arterial obstruction
thrombolysis
alteplase
blood pressure reduction
ENCHANTED trial

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Zhou, Z., Xia, C., Mair, G., Delcourt, C., Yoshimura, S., Liu, X., Chen, Z., Malavera, A., Carcel, C., Chen, X., Wang, X., Al-Shahi Salman, R., Robinson, T. G., Lindley, R. I., Chalmers, J., Wardlaw, J. M., Parsons, M. W., Demchuk, A. M., & Anderson, C. S. (2022). Thrombolysis outcomes according to arterial characteristics of acute ischemic stroke by alteplase dose and blood pressure target. International Journal of Stroke, 17(5), 566-575. https://doi.org/10.1177/17474930211025436

@article{bc26c543956f4152b4ebff2fb11a77d3,

title = "Thrombolysis outcomes according to arterial characteristics of acute ischemic stroke by alteplase dose and blood pressure target",

abstract = "BackgroundWe explored the influence of low-dose intravenous alteplase and intensive blood pressure lowering on outcomes of acute ischemic stroke according to status/location of vascular obstruction in participants of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED).MethodsENCHANTED was a multicenter, quasi-factorial, randomized trial to determine efficacy and safety of low- versus standard-dose intravenous alteplase and intensive- versus guideline-recommended blood pressure lowering in acute ischemic stroke patients. In those who had baseline computed tomography or magnetic resonance imaging angiography, the degree of vascular occlusion was grouped according to being no (NVO), medium (MVO), or large (LVO). Logistic regression models were used to determine 90-day outcomes (modified Rankin scale [mRS] shift [primary], other mRS cut-scores, intracranial hemorrhage, early neurologic deterioration, and recanalization) by vascular obstruction status/site. Heterogeneity in associations for outcomes across subgroups was estimated by adding an interaction term to the models.ResultsThere were 940 participants: 607 in alteplase arm only, 243 in blood pressure arm only, and 90 assigned to both arms. Compared to the NVO group, functional outcome was worse in LVO (mRS shift, adjusted OR [95% CI] 2.13 [1.56–2.90]) but comparable in MVO (1.34 [0.96–1.88]) groups. There were no differences in associations of alteplase dose or blood pressure lowering and outcomes across NVO/MVO/LVO groups (mRS shift: low versus standard alteplase dose 0.84 [0.54–1.30]/0.48 [0.25–0.91]/0.99 [0.75–2.09], Pinteraction = 0.28; intensive versus standard blood pressure lowering 1.32 [0.74–2.38]/0.78 [0.31–1.94]/1.24 [0.64–2.41], Pinteraction = 0.41), except for a borderline significant difference for intensive blood pressure lowering and increased early neurologic deterioration (0.63 [0.14–2.72]/0.17 [0.02–1.47]/2.69 [0.90–8.04], Pinteraction = 0.05).ConclusionsFunctional outcome by dose of alteplase or intensity of blood pressure lowering is not modified by vascular obstruction status/site according to analyses from ENCHANTED, although these results are compromised by low statistical power.",

keywords = "Acute ischemic stroke, arterial obstruction, thrombolysis, alteplase, blood pressure reduction, ENCHANTED trial",

author = "Zien Zhou and Chao Xia and Grant Mair and Candice Delcourt and S. Yoshimura and Xiaosheng Liu and Zengai Chen and A. Malavera and C. Carcel and Xiaoying Chen and Xia Wang and {Al-Shahi Salman}, R. and Robinson, {Thompson G.} and R.I. Lindley and John Chalmers and Wardlaw, {Joanna M.} and Parsons, {Mark W.} and A.M. Demchuk and Anderson, {Craig S.}",

year = "2022",

month = jun,

doi = "10.1177/17474930211025436",

language = "English",

volume = "17",

pages = "566--575",

journal = "International Journal of Stroke",

issn = "1747-4949",

publisher = "Blackwell Publishing Ltd",

number = "5",

}

Zhou, Z, Xia, C, Mair, G, Delcourt, C, Yoshimura, S, Liu, X, Chen, Z, Malavera, A, Carcel, C, Chen, X, Wang, X, Al-Shahi Salman, R, Robinson, TG, Lindley, RI, Chalmers, J, Wardlaw, JM, Parsons, MW, Demchuk, AM & Anderson, CS 2022, 'Thrombolysis outcomes according to arterial characteristics of acute ischemic stroke by alteplase dose and blood pressure target', International Journal of Stroke, vol. 17, no. 5, pp. 566-575. https://doi.org/10.1177/17474930211025436

TY - JOUR

T1 - Thrombolysis outcomes according to arterial characteristics of acute ischemic stroke by alteplase dose and blood pressure target

AU - Zhou, Zien

AU - Xia, Chao

AU - Mair, Grant

AU - Delcourt, Candice

AU - Yoshimura, S.

AU - Liu, Xiaosheng

AU - Chen, Zengai

AU - Malavera, A.

AU - Carcel, C.

AU - Chen, Xiaoying

AU - Wang, Xia

AU - Al-Shahi Salman, R.

AU - Robinson, Thompson G.

AU - Lindley, R.I.

AU - Chalmers, John

AU - Wardlaw, Joanna M.

AU - Parsons, Mark W.

AU - Demchuk, A.M.

AU - Anderson, Craig S.

PY - 2022/6

Y1 - 2022/6

N2 - BackgroundWe explored the influence of low-dose intravenous alteplase and intensive blood pressure lowering on outcomes of acute ischemic stroke according to status/location of vascular obstruction in participants of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED).MethodsENCHANTED was a multicenter, quasi-factorial, randomized trial to determine efficacy and safety of low- versus standard-dose intravenous alteplase and intensive- versus guideline-recommended blood pressure lowering in acute ischemic stroke patients. In those who had baseline computed tomography or magnetic resonance imaging angiography, the degree of vascular occlusion was grouped according to being no (NVO), medium (MVO), or large (LVO). Logistic regression models were used to determine 90-day outcomes (modified Rankin scale [mRS] shift [primary], other mRS cut-scores, intracranial hemorrhage, early neurologic deterioration, and recanalization) by vascular obstruction status/site. Heterogeneity in associations for outcomes across subgroups was estimated by adding an interaction term to the models.ResultsThere were 940 participants: 607 in alteplase arm only, 243 in blood pressure arm only, and 90 assigned to both arms. Compared to the NVO group, functional outcome was worse in LVO (mRS shift, adjusted OR [95% CI] 2.13 [1.56–2.90]) but comparable in MVO (1.34 [0.96–1.88]) groups. There were no differences in associations of alteplase dose or blood pressure lowering and outcomes across NVO/MVO/LVO groups (mRS shift: low versus standard alteplase dose 0.84 [0.54–1.30]/0.48 [0.25–0.91]/0.99 [0.75–2.09], Pinteraction = 0.28; intensive versus standard blood pressure lowering 1.32 [0.74–2.38]/0.78 [0.31–1.94]/1.24 [0.64–2.41], Pinteraction = 0.41), except for a borderline significant difference for intensive blood pressure lowering and increased early neurologic deterioration (0.63 [0.14–2.72]/0.17 [0.02–1.47]/2.69 [0.90–8.04], Pinteraction = 0.05).ConclusionsFunctional outcome by dose of alteplase or intensity of blood pressure lowering is not modified by vascular obstruction status/site according to analyses from ENCHANTED, although these results are compromised by low statistical power.

AB - BackgroundWe explored the influence of low-dose intravenous alteplase and intensive blood pressure lowering on outcomes of acute ischemic stroke according to status/location of vascular obstruction in participants of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED).MethodsENCHANTED was a multicenter, quasi-factorial, randomized trial to determine efficacy and safety of low- versus standard-dose intravenous alteplase and intensive- versus guideline-recommended blood pressure lowering in acute ischemic stroke patients. In those who had baseline computed tomography or magnetic resonance imaging angiography, the degree of vascular occlusion was grouped according to being no (NVO), medium (MVO), or large (LVO). Logistic regression models were used to determine 90-day outcomes (modified Rankin scale [mRS] shift [primary], other mRS cut-scores, intracranial hemorrhage, early neurologic deterioration, and recanalization) by vascular obstruction status/site. Heterogeneity in associations for outcomes across subgroups was estimated by adding an interaction term to the models.ResultsThere were 940 participants: 607 in alteplase arm only, 243 in blood pressure arm only, and 90 assigned to both arms. Compared to the NVO group, functional outcome was worse in LVO (mRS shift, adjusted OR [95% CI] 2.13 [1.56–2.90]) but comparable in MVO (1.34 [0.96–1.88]) groups. There were no differences in associations of alteplase dose or blood pressure lowering and outcomes across NVO/MVO/LVO groups (mRS shift: low versus standard alteplase dose 0.84 [0.54–1.30]/0.48 [0.25–0.91]/0.99 [0.75–2.09], Pinteraction = 0.28; intensive versus standard blood pressure lowering 1.32 [0.74–2.38]/0.78 [0.31–1.94]/1.24 [0.64–2.41], Pinteraction = 0.41), except for a borderline significant difference for intensive blood pressure lowering and increased early neurologic deterioration (0.63 [0.14–2.72]/0.17 [0.02–1.47]/2.69 [0.90–8.04], Pinteraction = 0.05).ConclusionsFunctional outcome by dose of alteplase or intensity of blood pressure lowering is not modified by vascular obstruction status/site according to analyses from ENCHANTED, although these results are compromised by low statistical power.

KW - Acute ischemic stroke

KW - arterial obstruction

KW - thrombolysis

KW - alteplase

KW - blood pressure reduction

KW - ENCHANTED trial

UR - http://www.scopus.com/inward/record.url?scp=85108789196&partnerID=8YFLogxK

U2 - 10.1177/17474930211025436

DO - 10.1177/17474930211025436

M3 - Article

SN - 1747-4949

VL - 17

SP - 566

EP - 575

JO - International Journal of Stroke

JF - International Journal of Stroke

IS - 5

ER -

Thrombolysis outcomes according to arterial characteristics of acute ischemic stroke by alteplase dose and blood pressure target

Abstract

Keywords

UN SDGs

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