Hemorrhagic transformation after large cerebral infarction in rats pretreated with dabigatran or warfarin

Il Kwon, Sunho An, Jayoung Kim, Seung Hee Yang, Joonsang Yoo, Jang Hyun Baek, Hyo Suk Nam, Young Dae Kim, Hye Sun Lee, Hyun Jung Choi, Jihoe Heo

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background and Purpose: It is uncertain whether hemorrhagic transformation (HT) after large cerebral infarction is less frequent in dabigatran users than warfarin users. We compared the occurrence of HT after large cerebral infarction among rats pretreated with dabigatran, warfarin, or placebo. Methods: This was a triple-blind, randomized, and placebo-controlled experiment. After treatment with warfarin (0.2 mg/kg), dabigatran (20 mg/kg), or saline for 7 days, Wistar rats were subjected to transient middle cerebral artery occlusion. As the primary outcome, HT was determined by gradient-recalled echo imaging. For the secondary outcome, intracranial hemorrhage was assessed via gradient-recalled echo imaging in surviving rats and via autopsy for dead rats. Results: Of 62 rats, there were 33 deaths (53.2%, 17 technical reasons). Of the intention-to-treat population, 33 rats underwent brain imaging. HT was less frequent in the dabigatran group than the warfarin group (placebo 2/14 [14%], dabigatran 0/10 [0%], and warfarin 9/9 [100%]; dabigatran versus warfarin; P<0.001). In all 62 rats, compared with the placebo (2/14 [14.3%]), the incidence of intracranial hemorrhage was significantly higher in the warfarin group (19/29 [65.5%]; P=0.003), but not in the dabigatran group (6/19 [31.6%]; P=0.420). Mortality was significantly higher in the warfarin group than the dabigatran group (79.3% versus 47.4%; P=0.022), but not related to the hemorrhage frequency. Conclusions: The risk of HT after a large cerebral infarction was significantly increased in rats pretreated with warfarin than those with dabigatran. However, the results here may not have an exact clinical translation.

Original languageEnglish
Pages (from-to)2865-2871
Number of pages7
JournalStroke
Volume48
Issue number10
DOIs
Publication statusPublished - 2017 Oct 1

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Cerebral Infarction
Warfarin
Placebos
Intracranial Hemorrhages
Dabigatran
Middle Cerebral Artery Infarction
Neuroimaging
Wistar Rats
Autopsy
Hemorrhage
Mortality
Incidence

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

Cite this

Kwon, Il ; An, Sunho ; Kim, Jayoung ; Yang, Seung Hee ; Yoo, Joonsang ; Baek, Jang Hyun ; Nam, Hyo Suk ; Kim, Young Dae ; Lee, Hye Sun ; Choi, Hyun Jung ; Heo, Jihoe. / Hemorrhagic transformation after large cerebral infarction in rats pretreated with dabigatran or warfarin. In: Stroke. 2017 ; Vol. 48, No. 10. pp. 2865-2871.
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title = "Hemorrhagic transformation after large cerebral infarction in rats pretreated with dabigatran or warfarin",
abstract = "Background and Purpose: It is uncertain whether hemorrhagic transformation (HT) after large cerebral infarction is less frequent in dabigatran users than warfarin users. We compared the occurrence of HT after large cerebral infarction among rats pretreated with dabigatran, warfarin, or placebo. Methods: This was a triple-blind, randomized, and placebo-controlled experiment. After treatment with warfarin (0.2 mg/kg), dabigatran (20 mg/kg), or saline for 7 days, Wistar rats were subjected to transient middle cerebral artery occlusion. As the primary outcome, HT was determined by gradient-recalled echo imaging. For the secondary outcome, intracranial hemorrhage was assessed via gradient-recalled echo imaging in surviving rats and via autopsy for dead rats. Results: Of 62 rats, there were 33 deaths (53.2{\%}, 17 technical reasons). Of the intention-to-treat population, 33 rats underwent brain imaging. HT was less frequent in the dabigatran group than the warfarin group (placebo 2/14 [14{\%}], dabigatran 0/10 [0{\%}], and warfarin 9/9 [100{\%}]; dabigatran versus warfarin; P<0.001). In all 62 rats, compared with the placebo (2/14 [14.3{\%}]), the incidence of intracranial hemorrhage was significantly higher in the warfarin group (19/29 [65.5{\%}]; P=0.003), but not in the dabigatran group (6/19 [31.6{\%}]; P=0.420). Mortality was significantly higher in the warfarin group than the dabigatran group (79.3{\%} versus 47.4{\%}; P=0.022), but not related to the hemorrhage frequency. Conclusions: The risk of HT after a large cerebral infarction was significantly increased in rats pretreated with warfarin than those with dabigatran. However, the results here may not have an exact clinical translation.",
author = "Il Kwon and Sunho An and Jayoung Kim and Yang, {Seung Hee} and Joonsang Yoo and Baek, {Jang Hyun} and Nam, {Hyo Suk} and Kim, {Young Dae} and Lee, {Hye Sun} and Choi, {Hyun Jung} and Jihoe Heo",
year = "2017",
month = "10",
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doi = "10.1161/STROKEAHA.117.017751",
language = "English",
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pages = "2865--2871",
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Kwon, I, An, S, Kim, J, Yang, SH, Yoo, J, Baek, JH, Nam, HS, Kim, YD, Lee, HS, Choi, HJ & Heo, J 2017, 'Hemorrhagic transformation after large cerebral infarction in rats pretreated with dabigatran or warfarin', Stroke, vol. 48, no. 10, pp. 2865-2871. https://doi.org/10.1161/STROKEAHA.117.017751

Hemorrhagic transformation after large cerebral infarction in rats pretreated with dabigatran or warfarin. / Kwon, Il; An, Sunho; Kim, Jayoung; Yang, Seung Hee; Yoo, Joonsang; Baek, Jang Hyun; Nam, Hyo Suk; Kim, Young Dae; Lee, Hye Sun; Choi, Hyun Jung; Heo, Jihoe.

In: Stroke, Vol. 48, No. 10, 01.10.2017, p. 2865-2871.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Hemorrhagic transformation after large cerebral infarction in rats pretreated with dabigatran or warfarin

AU - Kwon, Il

AU - An, Sunho

AU - Kim, Jayoung

AU - Yang, Seung Hee

AU - Yoo, Joonsang

AU - Baek, Jang Hyun

AU - Nam, Hyo Suk

AU - Kim, Young Dae

AU - Lee, Hye Sun

AU - Choi, Hyun Jung

AU - Heo, Jihoe

PY - 2017/10/1

Y1 - 2017/10/1

N2 - Background and Purpose: It is uncertain whether hemorrhagic transformation (HT) after large cerebral infarction is less frequent in dabigatran users than warfarin users. We compared the occurrence of HT after large cerebral infarction among rats pretreated with dabigatran, warfarin, or placebo. Methods: This was a triple-blind, randomized, and placebo-controlled experiment. After treatment with warfarin (0.2 mg/kg), dabigatran (20 mg/kg), or saline for 7 days, Wistar rats were subjected to transient middle cerebral artery occlusion. As the primary outcome, HT was determined by gradient-recalled echo imaging. For the secondary outcome, intracranial hemorrhage was assessed via gradient-recalled echo imaging in surviving rats and via autopsy for dead rats. Results: Of 62 rats, there were 33 deaths (53.2%, 17 technical reasons). Of the intention-to-treat population, 33 rats underwent brain imaging. HT was less frequent in the dabigatran group than the warfarin group (placebo 2/14 [14%], dabigatran 0/10 [0%], and warfarin 9/9 [100%]; dabigatran versus warfarin; P<0.001). In all 62 rats, compared with the placebo (2/14 [14.3%]), the incidence of intracranial hemorrhage was significantly higher in the warfarin group (19/29 [65.5%]; P=0.003), but not in the dabigatran group (6/19 [31.6%]; P=0.420). Mortality was significantly higher in the warfarin group than the dabigatran group (79.3% versus 47.4%; P=0.022), but not related to the hemorrhage frequency. Conclusions: The risk of HT after a large cerebral infarction was significantly increased in rats pretreated with warfarin than those with dabigatran. However, the results here may not have an exact clinical translation.

AB - Background and Purpose: It is uncertain whether hemorrhagic transformation (HT) after large cerebral infarction is less frequent in dabigatran users than warfarin users. We compared the occurrence of HT after large cerebral infarction among rats pretreated with dabigatran, warfarin, or placebo. Methods: This was a triple-blind, randomized, and placebo-controlled experiment. After treatment with warfarin (0.2 mg/kg), dabigatran (20 mg/kg), or saline for 7 days, Wistar rats were subjected to transient middle cerebral artery occlusion. As the primary outcome, HT was determined by gradient-recalled echo imaging. For the secondary outcome, intracranial hemorrhage was assessed via gradient-recalled echo imaging in surviving rats and via autopsy for dead rats. Results: Of 62 rats, there were 33 deaths (53.2%, 17 technical reasons). Of the intention-to-treat population, 33 rats underwent brain imaging. HT was less frequent in the dabigatran group than the warfarin group (placebo 2/14 [14%], dabigatran 0/10 [0%], and warfarin 9/9 [100%]; dabigatran versus warfarin; P<0.001). In all 62 rats, compared with the placebo (2/14 [14.3%]), the incidence of intracranial hemorrhage was significantly higher in the warfarin group (19/29 [65.5%]; P=0.003), but not in the dabigatran group (6/19 [31.6%]; P=0.420). Mortality was significantly higher in the warfarin group than the dabigatran group (79.3% versus 47.4%; P=0.022), but not related to the hemorrhage frequency. Conclusions: The risk of HT after a large cerebral infarction was significantly increased in rats pretreated with warfarin than those with dabigatran. However, the results here may not have an exact clinical translation.

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JF - Stroke

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