Efficacy of triple antiplatelet therapy (aspirin, clopidogrel, and cilostazol) in cerebral infarction presenting with hemiplegia: A case report and critical appraisal of current evidence
Keywords:
Cerebral infarction, Triple antiplatelet therapy, bleeding intracranial, hemiplegic motor deficitAbstract
Cerebral infarction, a type of stroke, occurs when blood vessels in the brain become occluded. Triple antiplatelet therapy (aspirin, clopidogrel, and cilostazol) has been used to prevent recurrent episodes in patients with cerebral infarction; however, it carries a risk of bleeding. In this case report, we demonstrated the effectiveness of triple antiplatelet therapy in a patient with cerebral infarction and hemiplegic motor deficits. A 38-year-old man presented with paralysis of the right side of his body and slurred speech after resting for 14 hours before hospital admission. He denied prior head trauma, fever, headache, nausea, or loss of consciousness. There was no history of hypertension, diabetes mellitus, or heart disease, but the patient reported smoking 24 cigarettes daily. A head CT scan revealed an infarction in the external capsule and left corona radiata. Cerebral angiography showed occlusion of the left lenticulostriate artery, a branch of the middle cerebral artery (MCA) at the M1 segment. The patient was treated with citicoline, mecobalamin, atorvastatin, and ranitidine, in addition to triple antiplatelet therapy (aspirin, clopidogrel, and cilostazol). After eight days of treatment, the motor strength in the right upper and lower extremities showed significant improvement. The use of triple antiplatelet therapy in cerebral infarction remains a controversial topic due to the associated risk of major bleeding. However, in this case, the administration of triple antiplatelet therapy, guided by the TARDIS study, resulted in a favorable clinical outcome.
References
1. Tadi P, Lui F. Acute stroke. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. Available from: https://www.ncbi.nlm.nih.gov/books/NBK535369/ [updated 2023 Feb 28].
2. Kuriakose D, Xiao Z. Pathophysiology and treatment of stroke: present status and future perspectives. Int J Mol Sci. 2020;21(20):7609. doi:10.3390/ijms21207609.
3. Lucotti S, Cerutti C, Soyer M, et al. Aspirin blocks formation of metastatic intravascular niches by inhibiting platelet-derived COX-1/thromboxane A2. J Clin Invest. 2019;129(5):1845–62. doi:10.1172/JCI121985.
4. Balinski AM, Preuss CV. Cilostazol. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. Available from: https://www.ncbi.nlm.nih.gov/books/NBK544363/ [updated 2022 Sep 21].
5. Beavers CJ, Naqvi IA. Clopidogrel. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470539/ [updated 2022 Jul 11].
6. Andrade JG, Deyell MW, Khoo C, Lee M, Humphries K, Cairns JA. Risk of bleeding on triple antithrombotic therapy after percutaneous coronary intervention/stenting: a systematic review and meta-analysis. Can J Cardiol. 2013;29(2):204–12. doi:10.1016/j.cjca.2012.06.012.
7. Adibhatla RM, Hatcher JF, Dempsey RJ. Citicoline: neuroprotective mechanisms in cerebral ischemia. J Neurochem. 2002;80(1):12–23. doi:10.1046/j.0022-3042.2001.00697.x.
8. Gupta JK, Sana QS. Potential benefits of methylcobalamin: a review. Austin J Pharmacol Ther. 2015;3(3):1076.
9. Zhao J, Zhang X, Dong L, Wen Y, Cui L. The many roles of statins in ischemic stroke. Curr Neuropharmacol. 2014;12(6):564–74. doi:10.2174/1570159X12666140923210929.
10. Morgan KA, Ahlawat R. Ranitidine. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532989/ [updated 2022 Dec 11].
11. Benjamin EJ, Muntner P, Alonso A, et al. heart disease and stroke statistics-2019 update: a report from the American Heart Association. Circulation. 2019;139(10): e56–528. doi:10.1161/CIR.0000000000000659. [published correction appears in Circulation. 2020;141(2):e33. doi:10.1161/CIR.0000000000000746].
12. Hurford R, Sekhar A, Hughes TAT, Muir KW. Diagnosis and management of acute ischaemic stroke. Pract Neurol. 2020;20(4):304–16. doi:10.1136/practneurol-2020-002557.
13. Kamarova M, Baig S, Patel H, et al. Antiplatelet use in ischemic stroke. Ann Pharmacother. 2022;56(10):1159–73. doi:10.1177/10600280211073009.
14. Iqbal AM, Lopez RA, Hai O. Antiplatelet medications. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Nov 7.
15. Willmot M, Zhao L, Heptinstall S, Bath P. Triple antiplatelet therapy for secondary prevention of recurrent ischemic stroke. J Stroke Cerebrovasc Dis. 2004;13(3):138–40. doi: 10.1016/j.jstrokecerebrovasdis.2004.03.001.
16. Sprigg N, Gray LJ, England T, et al. A randomised controlled trial of triple antiplatelet therapy (aspirin, clopidogrel and dipyridamole) in the secondary prevention of stroke: safety, tolerability and feasibility. PLoS One. 2008;3(8): e2852. doi: 10.1371/journal.pone.0002852.
17. TARDIS Trial Investigators, Krishnan K, Beridze M, et al. Safety and efficacy of intensive vs guideline antiplatelet therapy in high-risk patients with recent ischemic stroke or transient ischemic attack: rationale and design of the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) trial. Int J Stroke. 2015;10(7):1159–65. doi:10.1111/ijs.12538.
18. Geeganage C, Wilcox R, Bath PM. Triple antiplatelet therapy for preventing vascular events: a systematic review and meta-analysis. BMC Med. 2010; 8:36. doi:10.1186/1741-7015-8-36.
19. Maguida G, Shuaib A. Collateral circulation in ischemic stroke: an updated review. J Stroke. 2023;25(2):179–98. doi:10.5853/jos.2022.02936.
20. Ban M, Han X, Bao W, Zhang H, Zhang P. Evaluation of collateral status and outcome in patients with middle cerebral artery stenosis in late time window by CT perfusion imaging. Front Neurol. 2022; 13:991023. doi:10.3389/fneur.2022.991023.
21. Okyere B, Mills WA 3rd, Wang X, et al. EphA4/Tie2 crosstalk regulates leptomeningeal collateral remodeling following ischemic stroke. J Clin Invest. 2020;130(2):1024–35. doi:10.1172/JCI131493.
22. Bath PM, Woodhouse LJ, Appleton JP, et al. Triple versus guideline antiplatelet therapy to prevent recurrence after acute ischaemic stroke or transient ischaemic attack: the TARDIS RCT. Health Technol Assess. 2018;22(48):1–76. doi:10.3310/hta22480.
23. Kim TJ, Lee JS, Yoon JS, et al. Multiple antiplatelet therapy in ischemic stroke already on antiplatelet agents based on the linked big data for stroke. J Korean Med Sci. 2023;38(38): e294. doi:10.3346/jkms.2023.38. e294.
24. Wu Z, Liu AF, Zhou J, et al. The safety of triple antiplatelet therapy under thromboelastography guidance in patients undergoing stenting for ischemic cerebrovascular disease. J Neurointerv Surg. 2019;11(4):352–6. doi:10.1136/neurintsurg-2018-013987.
25. Woodhouse LJ, Appleton JP, Christensen H, et al. Bleeding with intensive versus guideline antiplatelet therapy in acute cerebral ischaemia. Sci Rep. 2023;13(1):11717. doi:10.1038/s41598-023-38474-2.
26. Jonas S, Grieco G. Potential value of triple antiplatelet therapy for secondary stroke prevention. Stroke. 2003;34(10): e182–3. doi: 10.1161/01.STR.0000092896.70446.87.
27. Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high-risk patients. BMJ. 2002;324(7329):71–86. doi:10.1136/bmj.324.7329.71. [published correction appears in BMJ. 2002;324(7330):141].
28. Wang MT, Tsai CK, Kuo SH, et al. The dipyridamole added to dual antiplatelet therapy in cerebral infarction after first acute myocardial infarction: a nationwide, case-control study. Front Neurol. 2018; 9:1003. doi:10.3389/fneur.2018.01003.
29. Liu L, Huang J, Zhang X, Tang X. Efficacy and safety of triple therapy versus dual antiplatelet therapy in patients with atrial fibrillation undergoing coronary stenting: a meta-analysis. PLoS One. 2018;13(6): e0199232. doi: 10.1371/journal.pone.0199232.
30. Gwyn JCV, Thomas MR, Kirchhof P. Triple antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention: a viewpoint. Eur Heart J Cardiovasc Pharmacother. 2017;3(3):157–62. doi:10.1093/ehjcvp/pvx002.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Muhammad Yunus Amran, Muhammad Akbar Yunus, M Fajrin Hidayah, Fitri Jafani La’biran, Siti Giranti Ardilia Gunadi, Irbab Hawari

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transfer of Copyright and Permission to Reproduce Parts of Published Papers.
Authors retain the copyright for their published work. No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent. Reproductions with commercial intent will require written permission and payment of royalties.

