Skip to main content Accessibility help
×
Hostname: page-component-78c5997874-m6dg7 Total loading time: 0 Render date: 2024-11-10T07:38:23.121Z Has data issue: false hasContentIssue false

Chapter 9 - Acute Antiplatelet Therapy for the Treatment of Ischaemic Stroke and Transient Ischaemic Attack

from Part III - Acute Treatment of Ischaemic Stroke and Transient Ischaemic Attack

Published online by Cambridge University Press:  15 December 2020

Jeffrey L. Saver
Affiliation:
David Geffen School of Medicine, University of Ca
Graeme J. Hankey
Affiliation:
University of Western Australia, Perth
Get access

Summary

Aspirin 160–300 mg daily started within 48 h of onset of acute ischaemic stroke is associated with a small beneficial reduction in recurrent ischaemic stroke (6 fewer per 1000 patients treated) and pulmonary embolism (1.5 fewer per 1000) that outweighs increased risk of bleeding (2 extra symptomatic ICHs and 4 extra major extracranial haemorrhages). The net effect is that, for every 1000 patients treated early with aspirin, 22 have reduced long-term disability, including 11 more achieving full recovery. Only two single antiplatelet regimens have been compared head to head against aspirin alone: cilostazol (a phosphodiesterase inhibitor) performed similarly to aspirin; ticagrelor (a GP IIa/IIIb receptor antagonist) showed tended to reduce ischaemic events but increased minor bleeding and dyspnea. In minor, non-cardioembolic ischaemic stroke or TIA, early dual antiplatelet therapy (DAPT) has shown advantages over early monotherapy. Most well-studied is clopidogrel and aspirin, with similar findings for dipyridamole and aspirin. DAPT reduces all-type (ischaemic and haemorrhagic) recurrent stroke (27 fewer per 1000 treated patients), but minimally increases major extracranial bleedings (3 more per 1000). Confining DAPT to the first 3 w maximizes the benefit to harm ratio. Anticoagulants alone and arterial-dose anticoagulants added to antiplatelet agents offer no net advantages over antiplatelet drugs alone. Venous prophylaxis-dose anticoagulants and aspirin, compared with aspirin alone, reduced recurrent ischaemic stroke more than it tend increased major extracranial haemorrhage.

Type
Chapter
Information
Stroke Prevention and Treatment
An Evidence-based Approach
, pp. 154 - 178
Publisher: Cambridge University Press
Print publication year: 2020

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abciximab Emergent Stroke Treatment Trial (AbESTT) Investigators. (2005). Emergency administration of abciximab for treatment of patients with acute ischemic stroke. Results of a randomized phase 2 trial. Stroke, 36, 880–90.Google Scholar
Abciximab in Ischemic Stroke (AIST) Investigators. (2000). Abciximab in acute ischemic stroke: a randomized, double-blind, placebo-controlled, dose-escalation study. Stroke, 31, 601–09.Google Scholar
Adams, HP Jr, Effron, MB, Torner, J, Davalos, A, Frayne, J, Teal, P, et al. (2008). Emergency administration of abciximab for treatment of patients with acute ischemic stroke: results of an international phase III trial: Abciximab in Emergency Treatment of Stroke Trial (AbESTT-II). Stroke, 39, 8799.CrossRefGoogle ScholarPubMed
Adeoye, O, Sucharew, H, Khoury, J, Vagal, A, Schmit, PA, Ewing, I, et al. (2015). Combined approach to lysis utilizing eptifibatide and recombinant tissue-type plasminogen activator in acute ischemic stroke – full dose regimen stroke trial. Stroke, 46, 2529–33.Google Scholar
Bath, PM, Cotton, D, Martin, RH, Palesch, Y, Yusuf, S, Sacco, R, et al.; PRoFESS Study Group. (2010). Effect of combined aspirin and extended-release dipyridamole versus clopidogrel on functional outcome and recurrence in acute, mild ischemic stroke: PRoFESS subgroup analysis. Stroke, 41, 732–8.CrossRefGoogle ScholarPubMed
Bath, PM, Woodhouse, LJ, Appleton, JP, Beridze, M, Christensen, H, Dineen, RA, et al.; TARDIS Investigators. (2018). Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomized, open-label, phase 3 superiority trial. Lancet, 391, 850–9.Google Scholar
Berge, E, Abdelnoor, M, Nakstad, PH, Sandset, PM. (2000). Low molecular-weight heparin versus aspirin in patients with acute ischaemic stroke and atrial fibrillation: a double-blind randomised study. HAEST Study Group. Heparin in Acute Embolic Stroke Trial. Lancet, 355, 1205–10.Google Scholar
Berge, E, Sandercock, PAG. (2002). Anticoagulants versus antiplatelet agents for acute ischaemic stroke. Cochrane Database Syst Rev, 4. CD003242.Google Scholar
CAST (Chinese Acute Stroke Trial) Collaborative Group. (1997). CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. Lancet, 349, 1641–9.Google Scholar
Chen, ZM, Sandercock, P, Pan, HC, Counsell, C, Collins, R, Liu, LS, et al. (2000). Indications for early aspirin use in acute ischemic stroke: a combined analysis of 40 000 randomized patients from the Chinese Acute Stroke Trial and the international stroke trial. On behalf of the CAST and IST collaborative groups. Stroke, 31, 1240–9.Google Scholar
Ciccone, A, Motto, C, Abraha, I, Cozzolino, F, Santilli, I. (2014). Glycoprotein IIb-IIIa inhibitors for acute ischaemic stroke. Cochrane Database Syst Rev, 3. CD005208. doi:10.1002/14651858.CD005208.pub3.Google Scholar
Ciuffetti, G, Aisa, G, Mercuri, M, Lombardini, R, Paltriccia, R, Neri, C, et al. (1990). Effects of ticlopidine on the neurologic outcome and the hemorheologic pattern in the post acute phase of ischemic stroke: a pilot study. Angiology, 41, 505–11.Google Scholar
Cranston, JS, Kaplan, BD, Saver, JL. (2017). Minimally clinically important difference for safe and simple novel acute ischemic stroke therapies. Stroke, 48, 2946–51.CrossRefGoogle Scholar
Dengler, R, Diener, H-C, Schwartz, A, Grond, M, Schumacher, H, Machnig, T, et al.; for the EARLY Investigators. (2010). Early treatment with aspirin plus extended-release dipyridamole for transient ischaemic attack or ischaemic stroke within 24 h of symptom onset (EARLY trial): a randomised, open-label, blinded-endpoint trial. Lancet Neurol, 9, 159–66.CrossRefGoogle ScholarPubMed
He, F, Xia, C, Zhang, JH, Li, XQ, Zhou, ZH, Li, FP, et al. (2015). Clopidogrel plus aspirin versus aspirin alone for preventing early neurological deterioration in patients with acute ischemic stroke. J Clin Neurosci, 22, 83–6.Google Scholar
International Stroke Trial Collaborative Group. (1997). The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. Lancet, 349, 1569–81.Google Scholar
Jing, J, Meng, X, Zhao, X, Liu, L, Wang, A, Pan, Y, et al. (2018). Dual antiplatelet therapy in transient ischemic attack and minor stroke with different infarction patterns: subgroup analysis of the CHANCE randomized clinical trial. JAMA Neurol, 75, 711–19.CrossRefGoogle ScholarPubMed
Johnston, SC, Amarenco, P, Albers, GW, Denison, H, Easton, JD, Evans, SR, et al; SOCRATES Steering Committee and Investigators. (2016). Ticagrelor versus aspirin in acute stroke or transient ischemic attack. N Engl J Med, 375, 3543.CrossRefGoogle ScholarPubMed
Johnston, SC, Easton, JD, Farrant, M, Barsan, W, Conwit, RA, Elm, JJ, et al.; Clinical Research Collaboration, Neurological Emergencies Treatment Trials Network, and the POINT Investigators. (2018). Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med, 379, 215–25.CrossRefGoogle ScholarPubMed
Johnston, SC, Leira, EC, Hansen, MD, Adams, HP Jr. (2003). Early recovery after cerebral ischemia risk of subsequent neurological deterioration. Ann Neurol, 54, 439–44.Google Scholar
Kennedy, J, Hill, MD, Ryckborst, KJ, Eliasziw, M, Demchuk, AM, Buchan, AM; FASTER Investigators. (2007). Fast assessment of stroke and transient ischaemic attack to prevent early recurrence (FASTER): a randomised controlled pilot trial. Lancet Neurol, 6, 961–9.CrossRefGoogle ScholarPubMed
Lee, YS, Bae, HJ, Kang, DW, Lee, SH, Yu, K, Park, JM, et al. (2011). Cilostazol in Acute Ischemic Stroke Treatment (CAIST Trial): a randomized double-blind non-inferiority trial. Cerebrovasc Dis, 32, 6571.Google Scholar
Liu, L, Wong, KS, Leng, X, Pu, Y, Wang, Y, Jing, J, et al.; CHANCE Investigators. (2015). Dual antiplatelet therapy in stroke and ICAS: subgroup analysis of CHANCE. Neurology, 85, 1154–62.CrossRefGoogle ScholarPubMed
Multicentre Acute Stroke Trial-Italy (MAST-I) Group. (1995). Randomised controlled trial of streptokinase, aspirin, and combination of both in treatment of acute ischaemic stroke. Lancet, 346, 1509–14.Google Scholar
Pan, Y, Jing, J, Chen, W, Meng, X, Li, H, Zhao, X, Liu, L, Wang, D, Johnston, SC, Wang, Y, Wang, Y; CHANCE Investigators. (2017a). Risks and benefits of clopidogrel-aspirin in minor stroke or TIA: time course analysis of CHANCE. Neurology, 88, 1906–11.Google Scholar
Pan, Y, Meng, X, Jing, J, Li, H, Zhao, X, Liu, L, et al; CHANCE Investigators. (2017b). Association of multiple infarctions and ICAS with outcomes of minor stroke and TIA. Neurology, 88, 1081–8.Google Scholar
Pancioli, AM, Adeoye, O, Schmit, PA, Khoury, J, Levine, SR, Tomsick, TA,et al.; CLEAR-ER Investigators. (2013). Combined approach to lysis utilizing eptifibatide and recombinant tissue plasminogen activator in acute ischemic stroke-enhanced regimen stroke trial. Stroke, 44, 2381–7.Google Scholar
Rödén-Jüllig, Å, Britton, M, Malmkvist, K, Leijd, B. (2003). Aspirin in the prevention of progressing stroke: a randomized controlled study. J Intern Med, 254, 584–90.Google Scholar
Sandercock, PAG, Counsell, C, Tseng, MC, Cecconi, E. (2014). Oral antiplatelet therapy for acute ischaemic stroke. Cochrane Database Syst Rev, 3. CD000029. doi:10.1002/14651858.CD000029.pub3.CrossRefGoogle ScholarPubMed
Siebler, M, Hennerici, MG, Schneider, D, von Reutern, GM, Seitz, RJ, Röther, J, et al. (2011). Safety of tirofiban in acute ischemic stroke: the SaTIS trial. Stroke, 42, 2388–92.Google Scholar
Thompson, DD, Murray, GD, Candelise, L, Chen, Z, Sandercock, PA, Whiteley, WN. (2015). Targeting aspirin in acute disabling ischemic stroke: an individual patient data meta-analysis of three large randomized trials. Int J Stroke, 10, 1024–30.Google Scholar
Torgano, G, Zecca, B, Monzani, V, Maestroni, A, Rossi, P, Cazzaniga, M, et al. (2010). Effect of intravenous tirofiban and aspirin in reducing short-term and long-term neurologic deficit in patients with ischemic stroke: a double-blind randomized trial. Cerebrovasc Dis, 29, 275–81.CrossRefGoogle ScholarPubMed
Wang, Y, Meng, X, Chen, W, Lin, Y, Pan, Y, Jing, J, et al.; PRiNCE Investigators. (2018). Ticagrelor with aspirin on platelet reactivity in acute non-disabling cerebrovascular events (PRINCE) trial – Final analysis. International Stroke Conference. https://professional.heart.org/idc/groups/ahamah-public/@wcm/@sop/@scon/documents/downloadable/ucm_498791.pdf. Accessed August 2018.Google Scholar
Wang, Y, Wang, Y, Zhao, X, Liu, L, Wang, D, Wang, C, et al.; CHANCE Investigators. (2013). Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med, 369, 1119.Google Scholar
Wang, Y, Zhao, X, Lin, J, Li, H, Johnston, SC, Lin, Y, et al.; CHANCE Investigators. (2016). 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, 316, 70–8.Google Scholar
Wong, KS, Chen, C, Ng, PW, Tsoi, TH, Li, HL, Fong, WC, et al.; FISS-tris Study Investigators. (2007). Low-molecular-weight heparin compared with aspirin for the treatment of acute ischaemic stroke in Asian patients with large artery occlusive disease: a randomised study. Lancet Neurol, 6, 407–13.Google Scholar
Wong, KS, Wang, Y, Leng, X, Mao, C, Tang, J, Bath, PM, et al. (2013). Early dual versus mono antiplatelet therapy for acute non-cardioembolic ischemic stroke or transient ischemic attack: an updated systematic review and meta-analysis. Circulation, 128, 1656–66.Google Scholar
Yang, Y, Zhou, M, Zhong, X, Wang, Y, Zhao, X, Liu, L, et al. (2018). Dual versus mono antiplatelet therapy for acute non-cardioembolic ischaemic stroke or transient ischaemic attack: a systematic review and meta-analysis. Stroke Vasc Neurol, 3, 107–16.Google Scholar
Yi, X, Lin, J, Wang, C, Zhang, B, Chi, W. (2014). Low-molecular-weight heparin is more effective than aspirin in preventing early neurologic deterioration and improving six-month outcome. J Stroke Cerebrovasc Dis, 23, 1537–44.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×