Intracranial Occlusion in Cryptogenic Stroke Is Not Predictive of Recurrent Ischemic Stroke: A Propensity-Score Matched Analysis of the Cardiac Abnormalities in Stroke Prevention and Risk of Recurrence Study

Matthew M. Smith; James R. Brorson; Elena Badillo Goicoechea; Mary Penckofer; Kelsey Eklund; Christoph Stretz; Christina M. Lineback; Farid Khasiyev; Deborah Kerrigan; Skylar Lewis; Hamid Ali; Hassan Aboul-Nour; Adam de Havenon; Collin J. Culbertson; Emiliya Melkumova; Dinesh Jillella; Oana M. Dumitrascu; Parth Parikh; Charles Doolittle; Ian Yahnke; Anvitha Sathya; Samantha Brown; Jieun Kang; Anna Bowman; Mahan Shahrivari; Cheran Elangovan; Siddharth Sehgal; Kelly L. Sloane; Muhammad Alvi; Balaji Krishnaiah; Wayneho Kam; Sachin Kothari; Ahmad Abu Qdais; Mudassir Farooqui; Fadi Nahab; Gustavo Antezana Quintela; Richa Sharma; Neeharika Thottempudi; Simona Nedelcu; Franziska Herpich; Patrick Glover; Dalia Chahien; David S. Liebeskind; Guillermo Linares; Jean Philippe Daniel; Sami Al Kasab; Eesha Singh; Marissa D’Souza; Elizabeth Gaudio; Yasmin Aziz; Shadi Yaghi; Narendra Kala; Monica Sarkar; Eric D. Goldsteinm; Lucia Chen; Russel Van Coevering; Jesse M. Thon; Brian Stamm; Sean L. Thompson; James E. Siegler

doi:10.1161/JAHA.125.041500

Intracranial Occlusion in Cryptogenic Stroke Is Not Predictive of Recurrent Ischemic Stroke: A Propensity-Score Matched Analysis of the Cardiac Abnormalities in Stroke Prevention and Risk of Recurrence Study

Matthew M. Smith
, James R. Brorson
, Elena Badillo Goicoechea
, Mary Penckofer
, Kelsey Eklund
, Christoph Stretz
, Christina M. Lineback
, Farid Khasiyev
, Deborah Kerrigan
, Skylar Lewis
, Hamid Ali
, Hassan Aboul-Nour
, Adam de Havenon
, Collin J. Culbertson
, Emiliya Melkumova
, Dinesh Jillella
, Oana M. Dumitrascu
, Parth Parikh
, Charles Doolittle
, Ian Yahnke

Anvitha Sathya, Samantha Brown, Jieun Kang, Anna Bowman, Mahan Shahrivari, Cheran Elangovan, Siddharth Sehgal, Kelly L. Sloane, Muhammad Alvi, Balaji Krishnaiah, Wayneho Kam, Sachin Kothari, Ahmad Abu Qdais, Mudassir Farooqui, Fadi Nahab, Gustavo Antezana Quintela, Richa Sharma, Neeharika Thottempudi, Simona Nedelcu, Franziska Herpich, Patrick Glover, Dalia Chahien, David S. Liebeskind, Guillermo Linares, Jean Philippe Daniel, Sami Al Kasab, Eesha Singh, Marissa D’Souza, Elizabeth Gaudio, Yasmin Aziz, Shadi Yaghi, Narendra Kala, Monica Sarkar, Eric D. Goldsteinm, Lucia Chen, Russel Van Coevering, Jesse M. Thon, Brian Stamm, Sean L. Thompson, James E. Siegler

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

Abstract

BACKGROUND: Intracranial occlusions in embolic stroke of undetermined source are histopathologically similar to cardiac sources of embolism. Whether patients with embolic stroke of undetermined source and intracranial occlusion benefit from anticoagulation is unknown. METHODS: A multicenter retrospective cohort of adults with cryptogenic stroke was queried for patients with proximal or medium/ distal vessel occlusion. The primary outcome was recurrent ischemic stroke, which was assessed in unadjusted and adjusted Cox proportional hazards models and repeated following 1:1 propensity score matching and biweight kernel density matching. RESULTS: Of the 2328 patients who were followed over a median of 1.31 years (interquartile range, 0.34–2.85), 999 (42.6%) had an intracranial occlusion. When compared with patients without an intracranial occlusion, those with an occlusion had fewer atherosclerotic vascular risk factors, more severe symptoms, and less severe cerebral microvascular disease. The rate of recurrent stroke was similar between patients with versus without an intracranial occlusion (6.8%/year [95% CI, 5.7–8.2] versus 7.0%/year [95% CI 6.0–8.1]; adjusted hazard ratio [HR], 1.09 [95% CI, 0.77–1.55]). There was no association between occlusion and recurrent stroke in the adjusted propensity score matching (HR, 1.01 [95% CI, 0.64–1.59]) or kernel density models (HR, 0.95 [95% CI, 0.62–1.45]). There was no interaction between occlusion and treatment with anticoagulation, sex, age, or high-risk sources of embolism for the primary outcome in the unmatched and matched analyses. CONCLUSIONS: Intracranial occlusion in patients with embolic stroke of undetermined source is not associated with a greater risk of recurrence when compared with patients without an intracranial occlusion. There was no difference in rate of recurrent stroke with anticoagulation when stratified by presence or absence of occlusion.

Original language	English (US)
Article number	e041500
Journal	Journal of the American Heart Association
Volume	14
Issue number	19
DOIs	https://doi.org/10.1161/JAHA.125.041500
State	Published - Sep 25 2025
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2025 The Author(s). Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

ESUS
LVO
cryptogenic stroke
embolism
recurrent stroke

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10.1161/JAHA.125.041500

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Smith, M. M., Brorson, J. R., Goicoechea, E. B., Penckofer, M., Eklund, K., Stretz, C., Lineback, C. M., Khasiyev, F., Kerrigan, D., Lewis, S., Ali, H., Aboul-Nour, H., de Havenon, A., Culbertson, C. J., Melkumova, E., Jillella, D., Dumitrascu, O. M., Parikh, P., Doolittle, C., ... Siegler, J. E. (2025). Intracranial Occlusion in Cryptogenic Stroke Is Not Predictive of Recurrent Ischemic Stroke: A Propensity-Score Matched Analysis of the Cardiac Abnormalities in Stroke Prevention and Risk of Recurrence Study. Journal of the American Heart Association, 14(19), Article e041500. https://doi.org/10.1161/JAHA.125.041500

Intracranial Occlusion in Cryptogenic Stroke Is Not Predictive of Recurrent Ischemic Stroke: A Propensity-Score Matched Analysis of the Cardiac Abnormalities in Stroke Prevention and Risk of Recurrence Study. / Smith, Matthew M.; Brorson, James R.; Goicoechea, Elena Badillo et al.
In: Journal of the American Heart Association, Vol. 14, No. 19, e041500, 25.09.2025.

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

Smith, MM, Brorson, JR, Goicoechea, EB, Penckofer, M, Eklund, K, Stretz, C, Lineback, CM, Khasiyev, F, Kerrigan, D, Lewis, S, Ali, H, Aboul-Nour, H, de Havenon, A, Culbertson, CJ, Melkumova, E, Jillella, D, Dumitrascu, OM, Parikh, P, Doolittle, C, Yahnke, I, Sathya, A, Brown, S, Kang, J, Bowman, A, Shahrivari, M, Elangovan, C, Sehgal, S, Sloane, KL, Alvi, M, Krishnaiah, B, Kam, W, Kothari, S, Qdais, AA, Farooqui, M, Nahab, F, Quintela, GA, Sharma, R, Thottempudi, N, Nedelcu, S, Herpich, F, Glover, P, Chahien, D, Liebeskind, DS, Linares, G, Daniel, JP, Al Kasab, S, Singh, E, D’Souza, M, Gaudio, E, Aziz, Y, Yaghi, S, Kala, N, Sarkar, M, Goldsteinm, ED, Chen, L, Van Coevering, R, Thon, JM, Stamm, B, Thompson, SL & Siegler, JE 2025, 'Intracranial Occlusion in Cryptogenic Stroke Is Not Predictive of Recurrent Ischemic Stroke: A Propensity-Score Matched Analysis of the Cardiac Abnormalities in Stroke Prevention and Risk of Recurrence Study', Journal of the American Heart Association, vol. 14, no. 19, e041500. https://doi.org/10.1161/JAHA.125.041500

Smith MM, Brorson JR, Goicoechea EB, Penckofer M, Eklund K, Stretz C et al. Intracranial Occlusion in Cryptogenic Stroke Is Not Predictive of Recurrent Ischemic Stroke: A Propensity-Score Matched Analysis of the Cardiac Abnormalities in Stroke Prevention and Risk of Recurrence Study. Journal of the American Heart Association. 2025 Sep 25;14(19):e041500. doi: 10.1161/JAHA.125.041500

@article{9617f1a17b35443d9ac014e69f21b2d7,

title = "Intracranial Occlusion in Cryptogenic Stroke Is Not Predictive of Recurrent Ischemic Stroke: A Propensity-Score Matched Analysis of the Cardiac Abnormalities in Stroke Prevention and Risk of Recurrence Study",

abstract = "BACKGROUND: Intracranial occlusions in embolic stroke of undetermined source are histopathologically similar to cardiac sources of embolism. Whether patients with embolic stroke of undetermined source and intracranial occlusion benefit from anticoagulation is unknown. METHODS: A multicenter retrospective cohort of adults with cryptogenic stroke was queried for patients with proximal or medium/ distal vessel occlusion. The primary outcome was recurrent ischemic stroke, which was assessed in unadjusted and adjusted Cox proportional hazards models and repeated following 1:1 propensity score matching and biweight kernel density matching. RESULTS: Of the 2328 patients who were followed over a median of 1.31 years (interquartile range, 0.34–2.85), 999 (42.6\%) had an intracranial occlusion. When compared with patients without an intracranial occlusion, those with an occlusion had fewer atherosclerotic vascular risk factors, more severe symptoms, and less severe cerebral microvascular disease. The rate of recurrent stroke was similar between patients with versus without an intracranial occlusion (6.8\%/year [95\% CI, 5.7–8.2] versus 7.0\%/year [95\% CI 6.0–8.1]; adjusted hazard ratio [HR], 1.09 [95\% CI, 0.77–1.55]). There was no association between occlusion and recurrent stroke in the adjusted propensity score matching (HR, 1.01 [95\% CI, 0.64–1.59]) or kernel density models (HR, 0.95 [95\% CI, 0.62–1.45]). There was no interaction between occlusion and treatment with anticoagulation, sex, age, or high-risk sources of embolism for the primary outcome in the unmatched and matched analyses. CONCLUSIONS: Intracranial occlusion in patients with embolic stroke of undetermined source is not associated with a greater risk of recurrence when compared with patients without an intracranial occlusion. There was no difference in rate of recurrent stroke with anticoagulation when stratified by presence or absence of occlusion.",

keywords = "ESUS, LVO, cryptogenic stroke, embolism, recurrent stroke",

author = "Smith, \{Matthew M.\} and Brorson, \{James R.\} and Goicoechea, \{Elena Badillo\} and Mary Penckofer and Kelsey Eklund and Christoph Stretz and Lineback, \{Christina M.\} and Farid Khasiyev and Deborah Kerrigan and Skylar Lewis and Hamid Ali and Hassan Aboul-Nour and \{de Havenon\}, Adam and Culbertson, \{Collin J.\} and Emiliya Melkumova and Dinesh Jillella and Dumitrascu, \{Oana M.\} and Parth Parikh and Charles Doolittle and Ian Yahnke and Anvitha Sathya and Samantha Brown and Jieun Kang and Anna Bowman and Mahan Shahrivari and Cheran Elangovan and Siddharth Sehgal and Sloane, \{Kelly L.\} and Muhammad Alvi and Balaji Krishnaiah and Wayneho Kam and Sachin Kothari and Qdais, \{Ahmad Abu\} and Mudassir Farooqui and Fadi Nahab and Quintela, \{Gustavo Antezana\} and Richa Sharma and Neeharika Thottempudi and Simona Nedelcu and Franziska Herpich and Patrick Glover and Dalia Chahien and Liebeskind, \{David S.\} and Guillermo Linares and Daniel, \{Jean Philippe\} and \{Al Kasab\}, Sami and Eesha Singh and Marissa D{\textquoteright}Souza and Elizabeth Gaudio and Yasmin Aziz and Shadi Yaghi and Narendra Kala and Monica Sarkar and Goldsteinm, \{Eric D.\} and Lucia Chen and \{Van Coevering\}, Russel and Thon, \{Jesse M.\} and Brian Stamm and Thompson, \{Sean L.\} and Siegler, \{James E.\}",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.",

year = "2025",

month = sep,

day = "25",

doi = "10.1161/JAHA.125.041500",

language = "English (US)",

volume = "14",

journal = "Journal of the American Heart Association",

issn = "2047-9980",

publisher = "American Heart Association Inc.",

number = "19",

}

TY - JOUR

T1 - Intracranial Occlusion in Cryptogenic Stroke Is Not Predictive of Recurrent Ischemic Stroke

T2 - A Propensity-Score Matched Analysis of the Cardiac Abnormalities in Stroke Prevention and Risk of Recurrence Study

AU - Smith, Matthew M.

AU - Brorson, James R.

AU - Goicoechea, Elena Badillo

AU - Penckofer, Mary

AU - Eklund, Kelsey

AU - Stretz, Christoph

AU - Lineback, Christina M.

AU - Khasiyev, Farid

AU - Kerrigan, Deborah

AU - Lewis, Skylar

AU - Ali, Hamid

AU - Aboul-Nour, Hassan

AU - de Havenon, Adam

AU - Culbertson, Collin J.

AU - Melkumova, Emiliya

AU - Jillella, Dinesh

AU - Dumitrascu, Oana M.

AU - Parikh, Parth

AU - Doolittle, Charles

AU - Yahnke, Ian

AU - Sathya, Anvitha

AU - Brown, Samantha

AU - Kang, Jieun

AU - Bowman, Anna

AU - Shahrivari, Mahan

AU - Elangovan, Cheran

AU - Sehgal, Siddharth

AU - Sloane, Kelly L.

AU - Alvi, Muhammad

AU - Krishnaiah, Balaji

AU - Kam, Wayneho

AU - Kothari, Sachin

AU - Qdais, Ahmad Abu

AU - Farooqui, Mudassir

AU - Nahab, Fadi

AU - Quintela, Gustavo Antezana

AU - Sharma, Richa

AU - Thottempudi, Neeharika

AU - Nedelcu, Simona

AU - Herpich, Franziska

AU - Glover, Patrick

AU - Chahien, Dalia

AU - Liebeskind, David S.

AU - Linares, Guillermo

AU - Daniel, Jean Philippe

AU - Al Kasab, Sami

AU - Singh, Eesha

AU - D’Souza, Marissa

AU - Gaudio, Elizabeth

AU - Aziz, Yasmin

AU - Yaghi, Shadi

AU - Kala, Narendra

AU - Sarkar, Monica

AU - Goldsteinm, Eric D.

AU - Chen, Lucia

AU - Van Coevering, Russel

AU - Thon, Jesse M.

AU - Stamm, Brian

AU - Thompson, Sean L.

AU - Siegler, James E.

N1 - Publisher Copyright: © 2025 The Author(s). Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

PY - 2025/9/25

Y1 - 2025/9/25

N2 - BACKGROUND: Intracranial occlusions in embolic stroke of undetermined source are histopathologically similar to cardiac sources of embolism. Whether patients with embolic stroke of undetermined source and intracranial occlusion benefit from anticoagulation is unknown. METHODS: A multicenter retrospective cohort of adults with cryptogenic stroke was queried for patients with proximal or medium/ distal vessel occlusion. The primary outcome was recurrent ischemic stroke, which was assessed in unadjusted and adjusted Cox proportional hazards models and repeated following 1:1 propensity score matching and biweight kernel density matching. RESULTS: Of the 2328 patients who were followed over a median of 1.31 years (interquartile range, 0.34–2.85), 999 (42.6%) had an intracranial occlusion. When compared with patients without an intracranial occlusion, those with an occlusion had fewer atherosclerotic vascular risk factors, more severe symptoms, and less severe cerebral microvascular disease. The rate of recurrent stroke was similar between patients with versus without an intracranial occlusion (6.8%/year [95% CI, 5.7–8.2] versus 7.0%/year [95% CI 6.0–8.1]; adjusted hazard ratio [HR], 1.09 [95% CI, 0.77–1.55]). There was no association between occlusion and recurrent stroke in the adjusted propensity score matching (HR, 1.01 [95% CI, 0.64–1.59]) or kernel density models (HR, 0.95 [95% CI, 0.62–1.45]). There was no interaction between occlusion and treatment with anticoagulation, sex, age, or high-risk sources of embolism for the primary outcome in the unmatched and matched analyses. CONCLUSIONS: Intracranial occlusion in patients with embolic stroke of undetermined source is not associated with a greater risk of recurrence when compared with patients without an intracranial occlusion. There was no difference in rate of recurrent stroke with anticoagulation when stratified by presence or absence of occlusion.

AB - BACKGROUND: Intracranial occlusions in embolic stroke of undetermined source are histopathologically similar to cardiac sources of embolism. Whether patients with embolic stroke of undetermined source and intracranial occlusion benefit from anticoagulation is unknown. METHODS: A multicenter retrospective cohort of adults with cryptogenic stroke was queried for patients with proximal or medium/ distal vessel occlusion. The primary outcome was recurrent ischemic stroke, which was assessed in unadjusted and adjusted Cox proportional hazards models and repeated following 1:1 propensity score matching and biweight kernel density matching. RESULTS: Of the 2328 patients who were followed over a median of 1.31 years (interquartile range, 0.34–2.85), 999 (42.6%) had an intracranial occlusion. When compared with patients without an intracranial occlusion, those with an occlusion had fewer atherosclerotic vascular risk factors, more severe symptoms, and less severe cerebral microvascular disease. The rate of recurrent stroke was similar between patients with versus without an intracranial occlusion (6.8%/year [95% CI, 5.7–8.2] versus 7.0%/year [95% CI 6.0–8.1]; adjusted hazard ratio [HR], 1.09 [95% CI, 0.77–1.55]). There was no association between occlusion and recurrent stroke in the adjusted propensity score matching (HR, 1.01 [95% CI, 0.64–1.59]) or kernel density models (HR, 0.95 [95% CI, 0.62–1.45]). There was no interaction between occlusion and treatment with anticoagulation, sex, age, or high-risk sources of embolism for the primary outcome in the unmatched and matched analyses. CONCLUSIONS: Intracranial occlusion in patients with embolic stroke of undetermined source is not associated with a greater risk of recurrence when compared with patients without an intracranial occlusion. There was no difference in rate of recurrent stroke with anticoagulation when stratified by presence or absence of occlusion.

KW - ESUS

KW - LVO

KW - cryptogenic stroke

KW - embolism

KW - recurrent stroke

UR - https://www.scopus.com/pages/publications/105018018570

UR - https://www.scopus.com/pages/publications/105018018570#tab=citedBy

U2 - 10.1161/JAHA.125.041500

DO - 10.1161/JAHA.125.041500

M3 - Article

C2 - 40996035

AN - SCOPUS:105018018570

SN - 2047-9980

VL - 14

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

IS - 19

M1 - e041500

ER -

Intracranial Occlusion in Cryptogenic Stroke Is Not Predictive of Recurrent Ischemic Stroke: A Propensity-Score Matched Analysis of the Cardiac Abnormalities in Stroke Prevention and Risk of Recurrence Study

Abstract

Bibliographical note

UN SDGs

Keywords

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