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Possibilities of antiplatelet therapy in non-cardioembolic ischemic stroke

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Most patients survive their first non-cardioembolic ischemic stroke (IS), but a significant proportion of them experience a second stroke within the first year. The main directions for the prevention of recurrent IS are antihypertensive and lipid-lowering therapy, control of glucose levels in patients with diabetes mellitus, and smoking cessation. Clinical guidelines recommend the use of antiplatelet therapy in patients with noncardioembolic IS or transient ischemic attack (TIA). The administration of antiplatelet agents to patients who have had a TIA or stroke reduces their risk of recurrent stroke by 23% and the overall risk of vascular events (myocardial infarction, stroke, and death from cardiovascular disease) by 17% (Antithrombotic Trialists' Collaboration, 2009). Acetylsalicylic acid (ASA), the combined use of clopidogrel and ASA, and the combination of ASA with sustained release dipyridamole have been shown to be effective for secondary prevention of non-cardioembolic IS. Intensive antiplatelet therapy reduces the risk of recurrent stroke, but increases the frequency of bleeding.

About the Authors

M. Yu. Maksimova
Research Center of Neurology
Russian Federation

80, Volokolamskoye Shosse, Moscow 125367

A. S. Airapetova
Research Center of Neurology
Russian Federation

80, Volokolamskoye Shosse, Moscow 125367


1. GBD 2016 Stroke Collaborators. Global, regional, and national burden of stroke, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019 May;18(5):439-58. doi: 10.1016/S1474-4422(19)30034-1. Epub 2019 Mar 11.

2. Flach C, Muruet W, Wolfe CDA, et al. Risk and Secondary Prevention of Stroke Recurrence: A Population-Base Cohort Study. Stroke. 2020 Aug;51(8):2435-44. doi: 10.1161/STROKEAHA.120.028992. Epub 2020 Jul 10.

3. Parfyonov VA, Verbitskaya SV. Antiplatelet therapy in secondary prevention of ischemic stroke. Meditsinskiy sovet = Medical Council. 2015;(5):6-13. doi: 10.21518/2079-701X-2015-5-6-13 (In Russ.).

4. Parfenov VA, Verbitskaya SV. Prevention of recurrent non-cardiac ischaemic stroke on the basis of antiplatelet agents. Aterotromboz. 2016;(2):89-97. doi: 10.21518/2307-1109-2016-2-89-97 (In Russ.).

5. Piradov MA, Tanashyan MM, Maksimova MYu, editors. Insul't: sovremennye tekhnologii diagnostiki i lecheniya: rukovodstvo dlya vrachey [Stroke: modern technologies for diagnosis and treatment: A guide for physicians]. Moscow: MEDpress-inform; 2018. 360 p. (In Russ.).

6. Domashenko MA, Maksimova MYu, Tanashyan MM. Modern view on the antiplatelet drugs appointment for secondary prevention of noncardioembolic ischemic stroke. Effektivnaya farmakoterapiya. 2018;24:82-6 (In Russ.).

7. Suslina ZA, Vysotskaya VG. Antiplatelet effect and clinical effect of low-dose aspirin in the treatment of patients with cerebrovascular pathology on the background of arterial hypertension. Klinicheskaya meditsina = Clinical Medicine. 1983;6(9):51-9 (In Russ.).

8. International Stroke Trial Collaborative Group. The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. Lancet. 1997 May 31;349(9065):1569-81.

9. CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group. Lancet. 1997 Jun 7;349(9066):1641-9.

10. Antithrombotic Trialists' (ATT) Collaboration; Baigent C, Blackwell L, Collins R, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009 May 30;373(9678):1849-60. doi: 10.1016/S0140-6736(09)60503-1

11. Goyan JE. The “trials” of a long-term clinical trial: the Ticlopidine Aspirin Stroke Study and the Canadian-American Ticlopidine Study. Control Clin Trials. 1989;10(4 Suppl):236S-244S. doi: 10.1016/0197-2456(89)90062-7

12. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996;348(9038):1329-39. doi: 10.1016/s0140-6736(96)09457-3

13. Diener HC, Bogousslavsky J, Brass LM, et al; MATCH investigators. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet. 2004;364(9431):331-7. doi: 10.1016/S0140-6736(04)16721-4

14. Bhatt DL, Flather MD, Hacke W, et al; CHARISMA Investigators. Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial. J Am Coll Cardiol. 2007 May 15;49(19):1982-8. doi: 10.1016/j.jacc.2007.03.025. Epub 2007 Apr 11.

15. Wang Y, Pan Y, Zhao X, et al; CHANCE Investigators. Clopidogrel With Aspirin in Acute Minor Stroke or Transient Ischemic Attack (CHANCE) Trial: One-Year Outcomes. Circulation. 2015 Jul 7;132(1):40-6. doi: 10.1161/CIRCULATIONAHA.114.014791. Epub 2015 May 8.

16. Amarenco P, Albers GW, Denison H, et al; SOCRATES Steering Committee and Investigators. Efficacy and safety of ticagrelor versus aspirin in acute stroke or transient ischaemic attack of atherosclerotic origin: a subgroup analysis of SOCRATES, a randomised, double-blind, controlled trial. Lancet Neurol. 2017 Apr;16(4):301-10. doi: 10.1016/S1474-4422(17)30038-8. Epub 2017 Feb 23.

17. Johnston SC, Amarenco P, Denison H, et al; THALES Investigators. The Acute Stroke or Transient Ischemic Attack Treated with Ticagrelor and Aspirin for Prevention of Stroke and Death (THALES) trial: Rationale and design. Int J Stroke. 2019 Oct;14(7):745-51. doi: 10.1177/1747493019830307. Epub 2019 Feb 12.

18. Best LC, McGuire MB, Jones PB, et al. Mode of action of dipyridamole on human platelets. Thromb Res. 1979;16(3-4):367-79. doi: 10.1016/0049-3848(79)90084-7

19. Wang C, Lin W, Playa H, et al. Dipyridamole analogs as pharmacological inhibitors of equilibrative nucleoside transporters. Identification of novel potent and selective inhibitors of the adenosine transporter function of human equilibrative nucleoside transporter 4 (hENT4). Biochem Pharmacol. 2013 Dec 1;86(11):1531-40. doi: 10.1016/j.bcp.2013.08.063. Epub 2013 Sep 7.

20. Dresse A, Chevolet C, Delapierre D, et al. Pharmacokinetics of oral dipyridamole (Persantine) and its effect on platelet adenosine uptake in man. Eur J Clin Pharmacol. 1982;23(3):229-34. doi: 10.1007/BF00547559

21. German DC, Kredich NM, Bjornsson TD. Oral dipyridamole increases plasma adenosine levels in human beings. Clin Pharmacol Ther. 1989 Jan;45(1):80-4. doi: 10.1038/clpt.1989.12

22. Kerndt CC, Nagalli S. Dipyridamole. 2021. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.2021 Nov 25.

23. Kareva EN. Features of the pharmacological actions and the use of dipyridamole in the prevention and treatment of viral infections. Consilium Medicum. 2016;18(12):80-7. doi: 10.26442/2075-1753_2016.12.80-87 (In Russ.).

24. Kim JA, Tran ND, Zhou W, Fisher M. Dipyridamole enhances tissue plasminogen activator release by brain capillary endothelial cells. Thromb Res. 2005;115(5):435-8. doi: 10.1016/j.thromres.2004.10.001. Epub 2004 Nov 5.

25. Costantini V, Talpacci A, Bastiano ML, et al. Increased prostacyclin production from human veins by dipyridamole: an in vitro and ex vivo study. Biomed Biochim Acta. 1990;49(4):263-71.

26. Long Y, Xia JY, Chen SW, et al. ATP2B1 gene Silencing Increases Insulin Sensitivity through Facilitating Akt Activation via the Ca2+/calmodulin Signaling Pathway and Ca2+-associated eNOS Activation in Endothelial Cells. Int J Biol Sci. 2017 Sep 5;13(9):1203-12. doi: 10.7150/ijbs.19666. eCollection 2017.

27. Pirahanchi Y, Dimri M. Biochemistry, Guanylate Cyclase. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.2021 Jul 22.

28. Kim HH, Liao JK. Translational therapeutics of dipyridamole. Arterioscler Thromb Vasc Biol. 2008 Mar;28(3):s39-42. doi: 10.1161/ATVBAHA.107.160226. Epub 2008 Jan 3.

29. Chakrabarti S, Vitseva O, Iyu D, et al. The effect of dipyridamole on vascular cellderived reactive oxygen species. J Pharmacol Exp Ther. 2005 Nov;315(2):494-500. doi: 10.1124/jpet.105.089987. Epub 2005 Jul 2.

30. European Stroke Prevention Study. ESPS Group. Stroke. 1990 Aug;21(8):1122-30. doi: 10.1161/01.str.21.8.1122

31. Diener HC, Cunha L, Forbes C, et al. European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci. 1996 Nov;143(1-2):1-13. doi: 10.1016/s0022-510x(96)00308-5

32. ESPRIT Study Group; Halkes PH, van Gijn J, Kappelle LJ, et al. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Lancet. 2006 May 20;367(9523):1665-73. doi: 10.1016/S0140-6736(06)68734-5

33. Diener HC, Sacco RL, Yusuf S, et al; Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) study group. Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial: a double-blind, active and placebo-controlled study. Lancet Neurol. 2008 Oct;7(10):875-84. doi: 10.1016/S1474-4422(08)70198-4. Epub 2008 Aug 29.

34. Sacco RL, Diener HC, Yusuf S, et al; PRoFESS Study Group. Aspirin and extendedrelease dipyridamole versus clopidogrel for recurrent stroke. N Engl J Med. 2008 Sep 18;359(12):1238-51. doi: 10.1056/NEJMoa0805002. Epub 2008 Aug 27.

35. Weintraub WS. The vascular effects of cilostazol. Can J Cardiol. 2006 Feb;22 Suppl B(Suppl B):56B-60B. doi: 10.1016/s0828-282x(06)70987-4

36. Tornyos D, Balint A, Kupo P, et al. Antithrombotic Therapy for Secondary Prevention in Patients with Non-Cardioembolic Stroke or Transient Ischemic Attack: A Systematic Review. Life (Basel). 2021 May 15;11(5):447. doi: 10.3390/life11050447

37. Albay CEQ, Leyson FGD, Cheng FC. Dual versus mono antiplatelet therapy for acute non-cardio embolic ischemic stroke or transient ischemic attack, an efficacy and safety analysis – updated meta-analysis. BMC Neurol. 2020 Jun 3;20(1):224. doi: 10.1186/s12883-020-01808-y

38. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2019 Dec;50(12):e344-e418. doi: 10.1161/STR.0000000000000211. Epub 2019 Oct 30.

39. Rahman H, Khan SU, Nasir F, et al. Optimal Duration of Aspirin Plus Clopidogrel After Ischemic Stroke or Transient Ischemic Attack. Stroke. 2019 Apr;50(4):947-53. doi: 10.1161/STROKEAHA.118.023978

40. Kleindorfer DO, Towfighi A, Chaturvedi S, et al. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2021 Jul;52(7):e364-e467. doi: 10.1161/STR.0000000000000375. Epub 2021 May 24.


For citations:

Maksimova M.Yu., Airapetova A.S. Possibilities of antiplatelet therapy in non-cardioembolic ischemic stroke. Neurology, Neuropsychiatry, Psychosomatics. 2022;14(3):81-86. (In Russ.)

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