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December 10, 2019

Lp-PLA2 and dual antiplatelet agents in intracranial arterial stenosis

Ming Yang, MD, Anxin Wang, PhD, Jiejie Li, MD, Xingquan Zhao, MD, Liping Liu, MD, Xia Meng, MD, Jing Jing, MD, Nan Zhang, PhD, S. Claiborne Johnston, MD, PhD, Yilong Wang, MD, and Yongjun Wang, MDAuthors Info & Affiliations
January 14, 2020 issue
94 (2) e181-e189
Letters to the Editor
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Abstract

Objective

To evaluate the interaction effect of lipoprotein-associated phospholipase A2 (Lp-PLA2) activity on the efficacy and safety of dual/single antiplatelet therapy in patients with and without intracranial arterial stenosis (ICAS) by the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events trial.

Methods

Patients with both MRI analysis and Lp-PLA2 testing results were included in the current subanalysis. The interaction of Lp-PLA2 activity with the effects of dual and single antiplatelet therapy were analyzed through Cox proportional hazards regressions model.

Results

Among the 797 patients, the mean age was 63.1 ± 10.8 years, 518 (65%) were men, 356 (44.7%) had ICAS, and 441 (55.3%) did not. There were significantly more patients with elevated Lp-PLA2 activity in the ICAS group than in the non-ICAS group (43.8% vs 35.4%, p = 0.02). There was significant interaction between Lp-PLA2 activity levels and the 2 antiplatelet therapies for prevention of stroke recurrences and combined vascular events even after adjustment for confounding factors exclusively for patients with ICAS (p = 0.017, 0.017, respectively), but not for those without (p = 0.332, 0.674, respectively). Compared with aspirin alone, dual antiplatelet therapy significantly reduced the risk of stroke recurrences and combined vascular events (adjusted hazard ratio 0.33 [0.12–0.89], p = 0.028; 0.33 [0.12–0.89], p = 0.028, respectively) for patients with ICAS and nonelevated Lp-PLA2 activity.

Conclusions

Presence of both ICAS and nonelevated Lp-PLA2 activity may predict better response to dual antiplatelet therapy in prevention of recurrent strokes and combined vascular events for patients with minor stroke or high-risk TIA.

Clinicaltrials.gov identifier

NCT00979589.

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Information & Authors

Information

Published In

Neurology®
Volume 94 • Number 2 • January 14, 2020
Pages: e181-e189

Copyright

© 2019 American Academy of Neurology.

Publication History

Received: January 8, 2019
Accepted: July 8, 2019
Published online: December 10, 2019
Published in print: January 14, 2020

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Authors

Affiliations & Disclosures

Ming Yang, MD*
From the Department of Neurology (M.Y., A.W., J.L., X.Z., L.L., X.M., J.J., N.Z., Yilong Wang, Yongjun Wang), Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Center of Stroke, Beijing Institute for Brain Disorders, China; and Dell Medical School (S.C.J.), University of Texas at Austin.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Anxin Wang, PhD*
From the Department of Neurology (M.Y., A.W., J.L., X.Z., L.L., X.M., J.J., N.Z., Yilong Wang, Yongjun Wang), Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Center of Stroke, Beijing Institute for Brain Disorders, China; and Dell Medical School (S.C.J.), University of Texas at Austin.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Jiejie Li, MD
From the Department of Neurology (M.Y., A.W., J.L., X.Z., L.L., X.M., J.J., N.Z., Yilong Wang, Yongjun Wang), Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Center of Stroke, Beijing Institute for Brain Disorders, China; and Dell Medical School (S.C.J.), University of Texas at Austin.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Xingquan Zhao, MD
From the Department of Neurology (M.Y., A.W., J.L., X.Z., L.L., X.M., J.J., N.Z., Yilong Wang, Yongjun Wang), Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Center of Stroke, Beijing Institute for Brain Disorders, China; and Dell Medical School (S.C.J.), University of Texas at Austin.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Liping Liu, MD
From the Department of Neurology (M.Y., A.W., J.L., X.Z., L.L., X.M., J.J., N.Z., Yilong Wang, Yongjun Wang), Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Center of Stroke, Beijing Institute for Brain Disorders, China; and Dell Medical School (S.C.J.), University of Texas at Austin.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
editor of Jouenals Stroke, Neuroepidemiology
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Xia Meng, MD
From the Department of Neurology (M.Y., A.W., J.L., X.Z., L.L., X.M., J.J., N.Z., Yilong Wang, Yongjun Wang), Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Center of Stroke, Beijing Institute for Brain Disorders, China; and Dell Medical School (S.C.J.), University of Texas at Austin.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Jing Jing, MD
From the Department of Neurology (M.Y., A.W., J.L., X.Z., L.L., X.M., J.J., N.Z., Yilong Wang, Yongjun Wang), Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Center of Stroke, Beijing Institute for Brain Disorders, China; and Dell Medical School (S.C.J.), University of Texas at Austin.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Nan Zhang, PhD
From the Department of Neurology (M.Y., A.W., J.L., X.Z., L.L., X.M., J.J., N.Z., Yilong Wang, Yongjun Wang), Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Center of Stroke, Beijing Institute for Brain Disorders, China; and Dell Medical School (S.C.J.), University of Texas at Austin.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
S. Claiborne Johnston, MD, PhD
From the Department of Neurology (M.Y., A.W., J.L., X.Z., L.L., X.M., J.J., N.Z., Yilong Wang, Yongjun Wang), Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Center of Stroke, Beijing Institute for Brain Disorders, China; and Dell Medical School (S.C.J.), University of Texas at Austin.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
$1500 - Duke University Honorarium $1500 - Rochester University
Funding for Travel or Speaker Honoraria:
1.
travel reimbursements 7/17 National Academies of Sciences 8/17 University of Utah Med School 10/17 National Academies of Sciences 11/17 AstraZeneca 12/17 University of Rochester NY 4/18 Duke University 5/18 New York University, Scheinberg Lecture + $500 honorarium 5/18 University of Cincinnati, Aring Lecture, all travel + honorarium 7/18 National Academies of Sciences 8/18 Summit Saúde Brasil 9/18 National Library of Medicine - Travel + $200 honorarium 10/18 National Academies of Sciences 10/18 The Association of Faculties of Medicine Symposium - Travel + 1500 honorarium 11/18 National Academy of Sciences Clinical Trials Workshop 3/19 National Academies of Sciences 5/19 National Library of Medicine
Editorial Boards:
1.
2006-present Chinese Journal of Stroke Editorial Board
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
AstraZeneca(PI), 2/1/13-1/31/16 SOCRATES: Acute Stroke Or Transient Ischemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes, $429,894, direct/yr 1, $5,069,962, direct/yrs 1-4. AstraZeneca (PI): Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death (THALES) SANOFI (PI): Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA (POINT), contributed drug and placebo to the NIH.
Research Support, Government Entities:
1.
UL1 RR024131 (PI), 9/30/06-6/30/16, NIH/NCATS, UCSF Clinical-Translational Science Institute, $13,104,012 direct/yr 1, $83,226,444 direct/yrs 1-10. U01 NS062835-01A1 (PI), 9/30/09-8/31/17, NIH/NINDS $4,841,588, direct/yr 1 POINT: Platelet-Oriented Inhibition in New TIA, $30,157,741 direct/yrs 1-5. U01 NS062835 (PI), NIH/NINDS, POINT: Platelet-Oriented Inhibition in New TIA, 05/01/2017-04/30/2021, $9,818,237, direct year 1 $22,841,251.
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Yilong Wang, MD
From the Department of Neurology (M.Y., A.W., J.L., X.Z., L.L., X.M., J.J., N.Z., Yilong Wang, Yongjun Wang), Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Center of Stroke, Beijing Institute for Brain Disorders, China; and Dell Medical School (S.C.J.), University of Texas at Austin.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
BMC Neurology, Associate Editor.
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
Ministry of Science and Technology of the People’s Republic of China,(2013BAI09B03, 2013BAI09B14, 2015BAI12B04, 2015BAI12B02, 2016YFC0901000, 2016YFC0901001, 2016YFC0901002), Leader investigator.
Research Support, Academic Entities:
1.
(1) Beijing Biobank of Cerebral Vascular Disease, (D131100005313003), Leader investigator, (2) Beijing Institute for Brain Disorders, (1152130306), Leader investigator.
Research Support, Foundations and Societies:
1.
National Natural Science Foundation of China, (No. 81673247, No.816005098),Leader investigator.
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Yongjun Wang, MD
From the Department of Neurology (M.Y., A.W., J.L., X.Z., L.L., X.M., J.J., N.Z., Yilong Wang, Yongjun Wang), Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Center of Stroke, Beijing Institute for Brain Disorders, China; and Dell Medical School (S.C.J.), University of Texas at Austin.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
Stroke and Vascular Neurology, Editor-in-chief, 2016-2018
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
Ministry of Science and Technology of the People’s Republic of China,(2013BAI09B03, 2013BAI09B14, 2015BAI12B04, 2015BAI12B02, 2016YFC0901000, 2016YFC0901001, 2016YFC0901002), Leader investigator.
Research Support, Academic Entities:
1.
(1) Beijing Biobank of Cerebral Vascular Disease, (D131100005313003), Leader investigator, (2) Beijing Institute for Brain Disorders, (1152130306), Leader investigator.
Research Support, Foundations and Societies:
1.
National Natural Science Foundation of China, (No. 81673247, No.816005098),Leader investigator.
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
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Notes

Correspondence Dr. Wang [email protected] or Dr. Wang [email protected]
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
*
These authors contributed equally to this work.

Disclosure

The authors report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.

Study Funding

Supported by grants from the Ministry of Science and Technology of the People's Republic of China (2015BAI12B04, 2015BAI12B02, 2016YFC0901000, 2016YFC0901001, and 2016YFC0901002) and grants from the Beijing Municipal Science and Technology Commission (D151100002015001, D151100002015002, D151100002015003, Z15110200390000, and Z151100003915117).

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