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Current Reviews in Clinical and Experimental Pharmacology


ISSN (Print): 2772-4328
ISSN (Online): 2772-4336

Systematic Review Article

Comparison of Aspirin and P2Y12 Inhibitors for Secondary Prevention of Ischaemic Stroke: A Systematic Review and Meta-analysis

Author(s): Kaili Zhang, Yongle Wang, Tingting Liu and Xiaoyuan Niu*

Volume 18, Issue 3, 2023

Published on: 11 August, 2022

Page: [270 - 283] Pages: 14

DOI: 10.2174/2772432817666220526162144

Price: $65


Background: P2Y12 inhibitors have been widely used as an alternative to aspirin in clinical practice for secondary stroke prevention. We aimed to compare the efficiency and safety of P2Y12 inhibitors and aspirin for stroke prevention in patients with previous stroke or transient ischaemic attack (TIA).

Methods: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched. All randomized trials that compared P2Y12 inhibitors with aspirin among patients with stroke were included. The primary efficacy outcomes of our meta-analysis included stroke, vascular events, and all-cause death. The primary safety outcome was minor or major bleeding events.

Results: The search identified 4 randomized clinical trials comparing P2Y12 inhibitors with aspirin for secondary stroke prevention that collectively enrolled 24508 patients (12253 received P2Y12 inhibitor and 12255 received aspirin). Pooled results from the random-effects model showed that there were no significant differences in the risk of any stroke (OR 0.90 (0.78-1.04); I²=56.9%), vascular event (OR 0.91 (0.74-1.13); I²=78.3%), all-cause death (OR 0.98 (0.83-1.17); I²=0%), or minor or major bleeding (OR 1.13 (0.70-1.82); I²=79%) among patients who received a P2Y12 inhibitor or aspirin. P2Y12 inhibitors were associated with a significantly lower risk of recurrent ischaemic stroke (OR 0.84 (0.73- 0.96); I²=25%) than aspirin.

Conclusion: This meta-analysis suggests that P2Y12 inhibitors are more effective than aspirin in preventing recurrent ischaemic stroke among ischaemic stroke patients despite the absence of any effect on a new ischaemic or haemorrhagic stroke, a new clinical vascular event, all-cause death, and major or minor bleeding events.

Keywords: P2Y12 inhibitor, aspirin, monotherapy, secondary prevention, ischaemic stroke, meta-analysis.

Katan M, Luft A. Global burden of stroke. Semin Neurol 2018; 38(2): 208-11.
[] [PMID: 29791947]
Tsai CF, Thomas B, Sudlow CL. Epidemiology of stroke and its subtypes in Chinese vs. white populations: A systematic review. Neurology 2013; 81(3): 264-72.
[] [PMID: 23858408]
Wang W, Jiang B, Sun H, et al. Prevalence, incidence, and mortality of stroke in China: Results from a nationwide population-based survey of 480687 adults. Circulation 2017; 135(8): 759-71.
[] [PMID: 28052979]
Caprio FZ, Sorond FA. Cerebrovascular disease: Primary and secondary stroke prevention. Med Clin North Am 2019; 103(2): 295-308.
[] [PMID: 30704682]
Chinese Society of N. Chinese Stroke S. Chinese guidelines for diagnosis and treatment of acute ischemic stroke 2018. Chin J Neurol 2018; 51: 666-82.
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; 50(12): e344-418.
[] [PMID: 31662037]
Chen ZM. CAST: Randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. Lancet 1997; 349(9066): 1641-9.
[] [PMID: 9186381]
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; 349(9065): 1569-81.
[] [PMID: 9174558]
Mensah GA, Wei GS, Sorlie PD, et al. Decline in cardiovascular mortality: Possible causes and implications. Circ Res 2017; 120(2): 366-80.
[] [PMID: 28104770]
Armstrong PC, Dhanji AR, Tucker AT, Mitchell JA, Warner TD. Reduction of platelet thromboxane A2 production ex vivo and in vivo by clopidogrel therapy. J Thromb Haemost 2010; 8(3): 613-5.
[] [PMID: 19995405]
Bhavaraju K, Georgakis A, Jin J, et al. Antagonism of P2Y12 reduces physiological thromboxane levels. Platelets 2010; 21(8): 604-9.
[] [PMID: 21067313]
Hass WK, Easton JD, Adams HP Jr, et al. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. N Engl J Med 1989; 321(8): 501-7.
[] [PMID: 2761587]
Gent M. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996; 348(9038): 1329-39.
[] [PMID: 8918275]
Gorelick PB, Richardson D, Kelly M, et al. Aspirin and ticlopidine for prevention of recurrent stroke in black patients: A randomized trial. JAMA 2003; 289(22): 2947-57.
[] [PMID: 12799402]
Johnston SC, Amarenco P, Albers GW, et al. Ticagrelor versus aspirin in acute stroke or transient ischemic attack. N Engl J Med 2016; 375(1): 35-43.
[] [PMID: 27160892]
Chiarito M, Sanz-Sánchez J, Cannata F, et al. Monotherapy with a P2Y12 inhibitor or aspirin for secondary prevention in patients with established atherosclerosis: A systematic review and meta-analysis. Lancet 2020; 395(10235): 1487-95.
[] [PMID: 32386592]
Adams HP Jr, Woolson RF, Biller J, Clarke W. Studies of Org 10172 in patients with acute ischemic stroke. Haemostasis 1992; 22(2): 99-103.
[PMID: 1379970]
Ueda M, Katayama Y. Characteristics and assessment of TOAST classification for diagnosing stroke subtypes. Jpn J Clin Med 2006; 64 (Suppl. 7): 56-60.
[PMID: 17461129]
Acheson RM. The etiology of coronary heart disease: A review from the epidemiological standpoint. Yale J Biol Med 1962; 35: 143-70.
[PMID: 14010850]
Higgins JP, Altman DG, Gøtzsche PC, et al. The cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011; 343(oct18 2): d5928.
[] [PMID: 22008217]
Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361(11): 1045-57.
[] [PMID: 19717846]
Franchi F, Rollini F, Aggarwal N, et al. Pharmacodynamic comparison of prasugrel versus ticagrelor in patients with type 2 diabetes mellitus and coronary artery disease: The OPTIMUS (Optimizing Antiplatelet Therapy in Diabetes Mellitus)-4 Study. Circulation 2016; 134(11): 780-92.
[] [PMID: 27559041]
Traby L, Kollars M, Kaider A, Eichinger S, Wolzt M, Kyrle PA. Effects of P2Y12 receptor inhibition with or without aspirin on hemostatic system activation: A randomized trial in healthy subjects. J Thromb Haemost 2016; 14(2): 273-81.
[] [PMID: 26663880]
Sudlow CL, Mason G, Maurice JB, Wedderburn CJ, Hankey GJ. Thienopyridine derivatives versus aspirin for preventing stroke and other serious vascular events in high vascular risk patients. Cochrane Database Syst Rev 2009; 2009(4): CD001246.
[] [PMID: 19821273]
Jia DM, Chen ZB, Zhang MJ, et al. CYP2C19 polymorphisms and antiplatelet effects of clopidogrel in acute ischemic stroke in China. Stroke 2013; 44(6): 1717-9.
[] [PMID: 23640828]
Wang Y, Zhao X, Lin J, et al. Association between CYP2C19 loss-of-function allele status and efficacy of clopidogrel for risk reduction among patients with minor stroke or transient ischemic attack. JAMA 2016; 316(1): 70-8.
[] [PMID: 27348249]
Kitzmiller JP, Groen DK, Phelps MA, Sadee W. Pharmacogenomic testing: Relevance in medical practice: Why drugs work in some patients but not in others. Cleve Clin J Med 2011; 78(4): 243-57.
[] [PMID: 21460130]
Scott SA, Sangkuhl K, Gardner EE, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450-2C19 (CYP2C19) genotype and clopidogrel therapy. Clin Pharmacol Ther 2011; 90(2): 328-32.
[] [PMID: 21716271]
Hasan MS, Basri HB, Hin LP, Stanslas J. Genetic polymorphisms and drug interactions leading to clopidogrel resistance: Why the Asian population requires special attention. Int J Neurosci 2013; 123(3): 143-54.
[] [PMID: 23110469]
Storey RF, Husted S, Harrington RA, et al. Inhibition of platelet aggregation by AZD6140, a reversible oral P2Y12 receptor antagonist, compared with clopidogrel in patients with acute coronary syndromes. J Am Coll Cardiol 2007; 50(19): 1852-6.
[] [PMID: 17980251]
Tourdot BE, Conaway S, Niisuke K, Edelstein LC, Bray PF, Holinstat M. Mechanism of race-dependent platelet activation through the protease-activated receptor-4 and Gq signaling axis. Arterioscler Thromb Vasc Biol 2014; 34(12): 2644-50.
[] [PMID: 25278289]
Amarenco P, Albers GW, Denison H, et al. 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; 16(4): 301-10.
[] [PMID: 28238711]
Purroy F, Montaner J, Molina CA, Delgado P, Ribo M, Alvarez-Sabín J. Patterns and predictors of early risk of recurrence after transient ischemic attack with respect to etiologic subtypes. Stroke 2007; 38(12): 3225-9.
[] [PMID: 17962602]
Amarenco P, Lavallée PC, Labreuche J, et al. One-year risk of stroke after transient ischemic attack or minor stroke. N Engl J Med 2016; 374(16): 1533-42.
[] [PMID: 27096581]
Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2018; 49(3): e46-e110.
[] [PMID: 29367334]

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