Skip to main content

Advertisement

SpringerLink
Log in

Low-dose antiplatelet therapy survey after intracerebral hemorrhage in China: a retrospective hospital-based study

  • Original Article
  • Published:
Neurosurgical Review Aims and scope Submit manuscript

Abstract

Restarting of antiplatelet therapy (AT) for patients with a history of intracerebral hemorrhage (ICH) is still a clinical dilemma in China. We aimed to investigate the association between low-dose AT and the long-term clinical outcome in Chinese ICH patients. A total of 312 patients with a history of ICH were retrospectively enrolled and followed. The ischemic vascular events, recurrent ICH, and all-cause death were reviewed retrospectively. We explored the predictors of ischemic vascular events and recurrent ICH from all patients using Cox proportional hazard regression model. One hundred fifty-one (48.4%) patients were treated with low-dose AT, and the median duration of follow-up was 4.0 years (interquartile range, 2.5–5 years). Compared to 30 (19.8%) of 151 participants who restarted low-dose AT had ischemic vascular events, 51 (31.7%) of 161 participants who did not receive AT showed ischemic vascular events (p=0.025). Eighteen (11.9%) of 151 participants treated with low-dose AT had recurrent ICH and 21 (13.0%) of 161 in non-AT participants (p=0.830). Cox regression analysis also showed that diabetes mellitus was an independent risk factor for ischemic vascular events (p=0.029). Uncontrolled blood pressure (BP) was independently associated with the risk for both ischemic vascular events (p=0.025) and recurrent ICH (p=0.001). Atrial fibrillation (AF) was an independent risk factor for recurrent ICH among patients with a history of ICH (p=0.018). In a Chinese population of patients with predominantly deep, mild to moderate severity ICH, restarting of low-dose AT at a median of 6.2 months was associated with a lower risk of ischemic vascular events without increased risk of recurrent ICH.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable

References

  1. Al-Shahi Salman R, Dennis MS, Murray GD, Innes K, Drever J, Dinsmore L, Williams C, White PM, Whiteley WN, Sandercock PAG, Sudlow CLM, Newby DE, Sprigg N, Werring DJ (2018) The REstart or STop Antithrombotics Randomised Trial (RESTART) after stroke due to intracerebral haemorrhage: study protocol for a randomised controlled trial. Trials 19. https://doi.org/10.1186/s13063-018-2542-6

  2. Biffi A, Anderson CD, Battey TW, Ayres AM, Greenberg SM, Viswanathan A, Rosand J (2015) Association between blood pressure control and risk of recurrent intracerebral hemorrhage. JAMA 314:904–912. https://doi.org/10.1001/jama.2015.10082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Chao TF, Liu CJ, Liao JN, Wang KL, Lin YJ, Chang SL, Lo LW, Hu YF, Tuan TC, Chung FP, Chen TJ, Lip GY, Chen SA (2016) Use of oral anticoagulants for stroke prevention in patients with atrial fibrillation who have a history of intracranial hemorrhage. Circulation 133:1540–1547. https://doi.org/10.1161/CIRCULATIONAHA.115.019794

    Article  CAS  PubMed  Google Scholar 

  4. Charidimou A, Kakar P, Fox Z, Werring DJ (2013) Cerebral microbleeds and recurrent stroke risk: systematic review and meta-analysis of prospective ischemic stroke and transient ischemic attack cohorts. Stroke 44:995–1001. https://doi.org/10.1161/STROKEAHA.111.000038

    Article  PubMed  Google Scholar 

  5. Ding X, Liu X, Tan C, Yin M, Wang T, Liu Y, Mo L, Wei X, Tan X, Deng F, Chen L (2018) Resumption of antiplatelet therapy in patients with primary intracranial hemorrhage-benefits and risks: a meta-analysis of cohort studies. J Neurol Sci 384:133–138. https://doi.org/10.1016/j.jns.2017.11.009

    Article  PubMed  Google Scholar 

  6. Eckman MH, Rosand J, Knudsen KA, Singer DE, Greenberg SM (2003) Can patients be anticoagulated after intracerebral hemorrhage? A decision analysis. Stroke 34:1710–1716. https://doi.org/10.1161/01.STR.0000078311.18928.16

    Article  PubMed  Google Scholar 

  7. Feigin VL, Lawes CMM, Bennett DA, Barker-Collo SL, Parag V (2009) Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol 8:355–369. https://doi.org/10.1016/s1474-4422(09)70025-0

    Article  PubMed  Google Scholar 

  8. Flynn RW, MacDonald TM, Murray GD, MacWalter RS, Doney AS (2010) Prescribing antiplatelet medicine and subsequent events after intracerebral hemorrhage. Stroke 41:2606–2611. https://doi.org/10.1161/STROKEAHA.110.589143

    Article  PubMed  Google Scholar 

  9. Gonzalez-Perez A, Gaist D, de Abajo FJ, Saez ME, Garcia Rodriguez LA (2017) Low-dose aspirin after an episode of haemorrhagic stroke is associated with improved survival. Thromb Haemost 117:2396–2405. https://doi.org/10.1160/TH17-05-0342

    Article  PubMed  Google Scholar 

  10. Goto S, Zhu J, Liu L, Oh BH, Wojdyla DM, Aylward P, Bahit MC, Gersh BJ, Hanna M, Horowitz J, Lopes RD, Wallentin L, Xavier D, Alexander JH, Investigators A (2014) Efficacy and safety of apixaban compared with warfarin for stroke prevention in patients with atrial fibrillation from East Asia: a subanalysis of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial. Am Heart J 168:303–309. https://doi.org/10.1016/j.ahj.2014.06.005

    Article  CAS  PubMed  Google Scholar 

  11. Hawkes MA, Rabinstein AA (2018) Anticoagulation for atrial fibrillation after intracranial hemorrhage: a systematic review. Neurol Clin Pract 8:48–57. https://doi.org/10.1212/CPJ.0000000000000425

    Article  PubMed  PubMed Central  Google Scholar 

  12. Hemphill JC 3rd, Bonovich DC, Besmertis L, Manley GT, Johnston SC (2001) The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke 32:891–897. https://doi.org/10.1161/01.str.32.4.891

    Article  PubMed  Google Scholar 

  13. Horstmann S, Mohlenbruch M, Wegele C, Rizos T, Laible M, Rauch G, Veltkamp R (2015) Prevalence of atrial fibrillation and association of previous antithrombotic treatment in patients with cerebral microbleeds. Eur J Neurol 22:1355–1362. https://doi.org/10.1111/ene.12608

    Article  CAS  PubMed  Google Scholar 

  14. Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD, Fang MC, Fisher M, Furie KL, Heck DV, Johnston SC, Kasner SE, Kittner SJ, Mitchell PH, Rich MW, Richardson D, Schwamm LH, Wilson JA, American Heart Association Stroke Council CoC, Stroke Nursing CoCC, Council on Peripheral Vascular D (2014) Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 45:2160–2236. https://doi.org/10.1161/STR.0000000000000024

    Article  PubMed  Google Scholar 

  15. Ka Sing LW, Hu DY, Oomamn A, Tan RS, Patel MR, Singer DE, Breithardt G, Mahaffey KW, Becker RC, Califf R, Fox KA, Berkowitz SD, Hacke W, Hankey GJ, Investigators ESCatRAS (2014) Rivaroxaban for stroke prevention in East Asian patients from the ROCKET AF trial. Stroke 45:305–310. https://doi.org/10.1161/STROKEAHA

    Article  Google Scholar 

  16. Murthy SB, Biffi A, Falcone GJ, Sansing LH, Torres Lopez V, Navi BB, Roh DJ, Mandava P, Hanley DF, Ziai WC, Kamel H, Rosand J, Sheth KN, Collaborators V-ISC (2019) Antiplatelet therapy after spontaneous intracerebral hemorrhage and functional outcomes. Stroke 50:3057–3063. https://doi.org/10.1161/STROKEAHA.119.025972

    Article  PubMed  PubMed Central  Google Scholar 

  17. Nielsen PB, Larsen TB, Skjoth F, Gorst-Rasmussen A, Rasmussen LH, Lip GY (2015) Restarting anticoagulant treatment after intracranial hemorrhage in patients with atrial fibrillation and the impact on recurrent stroke, mortality, and bleeding: a nationwide cohort study. Circulation 132:517–525. https://doi.org/10.1161/CIRCULATIONAHA.115.015735

    Article  CAS  PubMed  Google Scholar 

  18. Ohkubo K, Fujimoto Y, Iwata Y, Kitahara H, Kadohira T, Sugimoto K, Morino T, Kobayashi Y (2014) Efficacy and safety of low-dose clopidogrel in Japanese patients after drug-eluting stent implantation: a randomized pilot trial. Heart Vessel 29:1–6. https://doi.org/10.1007/s00380-012-0318-6

    Article  Google Scholar 

  19. Ohkubo K, Kobayashi Y (2011) Long-term safety and efficacy of low-dose clopidogrel in Japanese patients undergoing coronary stenting: a preliminary study. Cardiovasc Interv Ther 26:104–108. https://doi.org/10.1007/s12928-010-0043-y

    Article  CAS  PubMed  Google Scholar 

  20. Olesen JB, Lip GY, Hansen ML, Hansen PR, Tolstrup JS, Lindhardsen J, Selmer C, Ahlehoff O, Olsen AM, Gislason GH, Torp-Pedersen C (2011) Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study. Bmj 342:d124. https://doi.org/10.1136/bmj.d124

    Article  PubMed  PubMed Central  Google Scholar 

  21. Ottosen TP, Grijota M, Hansen ML, Brandes A, Damgaard D, Husted SE, Johnsen SP (2016) Use of antithrombotic therapy and long-term clinical outcome among patients surviving intracerebral hemorrhage. Stroke 47:1837–1843. https://doi.org/10.1161/STROKEAHA.116.012945

    Article  CAS  PubMed  Google Scholar 

  22. Pasquini M, Charidimou A, van Asch CJ, Baharoglu MI, Samarasekera N, Werring DJ, Klijn CJ, Roos YB, Al-Shahi Salman R, Cordonnier C (2014) Variation in restarting antithrombotic drugs at hospital discharge after intracerebral hemorrhage. Stroke 45:2643–2648. https://doi.org/10.1161/STROKEAHA.114.006202

    Article  CAS  PubMed  Google Scholar 

  23. Pennlert J, Asplund K, Carlberg B, Wiklund PG, Wisten A, Asberg S, Eriksson M (2015) antithrombotic treatment following intracerebral hemorrhage in patients with and without atrial fibrillation. Stroke 46:2094–2099. https://doi.org/10.1161/STROKEAHA.115.009087

    Article  CAS  PubMed  Google Scholar 

  24. Poon MT, Fonville AF, Al-Shahi Salman R (2014) Long-term prognosis after intracerebral haemorrhage: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 85:660–667. https://doi.org/10.1136/jnnp-2013-306476

    Article  PubMed  Google Scholar 

  25. Saito T, Kawamura Y, Tanabe Y, Asanome A, Takahashi K, Sawada J, Katayama T, Sato N, Aizawa H, Hasebe N (2014) Cerebral microbleeds and asymptomatic cerebral infarctions in patients with atrial fibrillation. J Stroke Cerebrovasc Dis 23:1616–1622. https://doi.org/10.1016/j.jstrokecerebrovasdis.2014.01.005

    Article  PubMed  Google Scholar 

  26. Teo KC, Lau GKK, Mak RHY, Leung HY, Chang RSK, Tse MY, Lee R, Leung GKK, Ho SL, Cheung RTF, Siu DCW, Chan KH (2017) Antiplatelet resumption after antiplatelet-related intracerebral hemorrhage: a retrospective hospital-based study. World Neurosurg 106:85–91. https://doi.org/10.1016/j.wneu.2017.06.015

    Article  PubMed  Google Scholar 

  27. Tun NN, Arunagirinathan G, Munshi SK, Pappachan JM (2017) Diabetes mellitus and stroke: a clinical update. World J Diabetes 8:235–248. https://doi.org/10.4239/wjd.v8.i6.235

    Article  PubMed  PubMed Central  Google Scholar 

  28. van Asch CJJ, Luitse MJA, Rinkel GJE, van der Tweel I, Algra A, Klijn CJM (2010) Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol 9:167–176. https://doi.org/10.1016/s1474-4422(09)70340-0

    Article  Google Scholar 

  29. van Etten ES, Auriel E, Haley KE, Ayres AM, Vashkevich A, Schwab KM, Rosand J, Viswanathan A, Greenberg SM, Gurol ME (2014) Incidence of symptomatic hemorrhage in patients with lobar microbleeds. Stroke 45:2280–2285. https://doi.org/10.1161/STROKEAHA.114.005151

    Article  PubMed  PubMed Central  Google Scholar 

  30. Jia WH, Zhou LC (2011) Use of antiplatelets. A survey of secondary prevention of ischemic stroke with intracranial hemorrhage history in Chinese patients. Neurosciences (Riyadh) 16:335–339

    Article  Google Scholar 

  31. Yamashita T, Koretsune Y, Yang Y, Chen SA, Chung N, Shimada YJ, Kimura T, Miyazaki K, Abe K, Mercuri M, Ruff CT, Giugliano RP (2016) Edoxaban vs. warfarin in east Asian patients with atrial fibrillation- an ENGAGE AF-TIMI 48 subanalysis. Circ J 80:860–869. https://doi.org/10.1253/circj.CJ-15-1082

    Article  CAS  PubMed  Google Scholar 

  32. Zazulia A (2015) Antiplatelet and anticoagulant therapy after intracerebral hemorrhage. Neurol Clin 33:329–345. https://doi.org/10.1016/j.ncl.2014.12.005

    Article  PubMed  Google Scholar 

Download references

Funding

This study was supported by the Wu Jieping Medical Foundation of China (No: 320.675.1279), the National Natural Science Foundation of China (81501483), and Shanghai Natural Science Foundation (18ZR1435400).

Author information

Author notes

  1. Xiangke Ma and Dongtao Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University, No. 5 Jingyuan Road, Beijing, 100043, China

    Xiangke Ma

  2. Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University, No. 5 Jingyuan Road, Beijing, 100043, China

    Dongtao Liu, Changqing Li & Lichun Zhou

  3. Department of Neurosurgery, Linyi People’s Hospital, No. 105, Guangchang Street, Dezhou City, 251500, Shandong Province, China

    Siqiang Niu

  4. Department of Echocardiography, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China

    Wei Zhao, Xifang Song & Jing Ma

  5. Department of Neurology, Shijingshan Teaching Hospital, Beijing Shijingshan Hospital, Capital Medical University, No. 24, Shijingshan Road, Beijing, 100041, China

    Weihua Jia

Authors
  1. Xiangke Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dongtao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Siqiang Niu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wei Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xifang Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Changqing Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lichun Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jing Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Weihua Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

DL, XM, and SN contributed to the preparation of the manuscript and data collection. WZ, XS, CL, LZ, and JM contributed to data analysis and interpretation. DL and WJ contributed to the experimental design and manuscript revision.

Corresponding authors

Correspondence to Xiangke Ma or Weihua Jia.

Ethics declarations

Ethics approval

Approval for the retrospective study was obtained from the research ethic committee and Institutional Review Board (IRB) of Beijing Chaoyang Hospital and Beijing Shijingshan Hospital, Capital Medical University.

Consent to participate

Due to a retrospective analysis of collected data, additional informed consent was deemed unnecessary.

Consent for publication

All authors of this manuscript also consent to the publication of the manuscript in Neurosurgical Review journal.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ma, X., Liu, D., Niu, S. et al. Low-dose antiplatelet therapy survey after intracerebral hemorrhage in China: a retrospective hospital-based study. Neurosurg Rev 44, 2923–2931 (2021). https://doi.org/10.1007/s10143-021-01483-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10143-021-01483-8

Keywords

Search

Navigation