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Chapter 19 - Long-term Antithrombotic Therapy for Large and Small Artery Occlusive Disease

from Part V - Prevention

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
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Summary

Long-term (>1 year) single antiplatelet therapy with aspirin is effective in reducing the risk of any early recurrent stroke by about one-sixth compared with no antiplatelet therapy. Clopidogrel monotherapy is marginally but significantly more effective than aspirin in reducing major vascular events. Cilostazol is also more effective than aspirin in Asian patients, and its therapeutic efficacy may be augmented by the addition of probucol in patients with ischaemic stroke and high risk of cerebral haemorrhage. The safety and effectiveness of cilostazol in non-Asian patients is not known. Prasugrel monotherapy (3.75 mg daily) is not non-inferior to clopidogrel monotherapy among Japanese patients with non-cardioembolic ischaemic stroke. Dual antiplatelet therapy with aspirin and extended-release dipyridamole is more effective than aspirin monotherapy and equally effective as clopidogrel monotherapy in preventing recurrent stroke. Dual antiplatelet therapy with aspirin and clopidogrel is more effective than aspirin monotherapy in preventing recurrent ischaemic stroke and myocardial infarction in high vascular risk patients, but it also increases the risk of major bleeding which may offset its benefits. Dual antiplatelet therapy with cilostazol added to aspirin or clopidogrel is more effective, and as safe as, aspirin or clopidogrel monotherapy in Japanese patients with non-cardioembolic ischaemic stroke.

Type
Chapter
Information
Stroke Prevention and Treatment
An Evidence-based Approach
, pp. 384 - 411
Publisher: Cambridge University Press
Print publication year: 2020

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References

Amarenco, P, Davis, S, Jones, EF, Cohen, AA, Heiss, WD, Kaste, M, et al.; Aortic Arch Related Cerebral Hazard Trial Investigators. (2014). Clopidogrel plus aspirin versus warfarin in patients with stroke and aortic arch plaques. Stroke, 45, 1248–57Google Scholar
Anand, SS, Bosch, J, Eikelboom, JW, Connolly, SJ, Diaz, R, Widimsky, P, et al.; COMPASS Investigators. (2018). Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet, 391, 219–29.CrossRefGoogle ScholarPubMed
Antithrombotic Trialists’ (ATT) Collaboration, Baigent, C, Blackwell, L, Collins, R, Emberson, J, Godwin, J, Peto, R, et al. (2009). Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet, 373, 1849–60.Google ScholarPubMed
Bhatt, DL, Fox, KA, Hacke, W, Berger, PB, Black, HR, Boden, WE, et al.; CHARISMA Investigators. (2006). Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med, 354,1706–17CrossRefGoogle ScholarPubMed
Bhatt, DL, Paré, G, Eikelboom, JW, Simonsen, KL, Emison, ES, Fox, KA, et al.; CHARISMA Investigators. (2012). The relationship between CYP2C19 polymorphisms and ischaemic and bleeding outcomes in stable outpatients: the CHARISMA genetics study. Eur Heart J, 33, 2143–50.Google Scholar
Bousser, MG, Amarenco, P, Chamorro, A, Fisher, M, Ford, I, Fox, KM, et al., for the PERFORM Study Investigators. (2011). Terutroban versus aspirin in patients with cerebral ischaemic events (PERFORM): a randomised, double-blind, parallel-group trial. Lancet, 377, 2013–22. Erratum in: Lancet, 378, 402.CrossRefGoogle ScholarPubMed
CAPRIE Steering Committee. (1996) A randomised, blinded trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet, 348, 1329–39.Google Scholar
Costa, J, Ferro, J, Matias-Guiu, J, Alvarez-Sabin, J, Torres, F. (2005). Triflusal for preventing serious vascular events in people at high risk. Cochrane Database Syst Rev, 3. CD004296.Google Scholar
De Schryver, ELLM, Algra, A, vanGijn, J. (2007). Dipyridamole for preventing stroke and other vascular events in patients with vascular disease. Cochrane Database Syst Rev, 3. CD001820. doi:10.1002/14651858.CD001820.pub3.CrossRefGoogle ScholarPubMed
De Schryver, ELLM, Algra, A, Kappelle, LJ, van Gijn, J, Koudstaal, PJ. (2012). Vitamin K antagonists versus antiplatelet therapy after transient ischaemic attack or minor ischaemic stroke of presumed arterial origin. Cochrane Database Syst Rev, 9. CD001342. doi:10.1002/14651858.CD001342.pub3.CrossRefGoogle ScholarPubMed
Diener, HC, Bogousslavsky, J, Brass, LM, Cimminiello, C, Csiba, L, Kaste, M, et al.; MATCH Investigators. (2004). 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, 364, 331–7.Google Scholar
Diener, HC, Cunha, L, Forbes, C, Sivenius, J, Smets, P, Lowenthal, A. (1996). European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci, 143, 1-13.Google Scholar
Diener, HC, Easton, JD, Granger, CB, Cronin, L, Duffy, C, Cotton, D, et al.; RE-SPECT ESUS Investigators. (2015). Design of Randomized, double-blind, Evaluation in secondary Stroke Prevention comparing the EfficaCy and safety of the oral Thrombin inhibitor dabigatran etexilate vs. acetylsalicylic acid in patients with Embolic Stroke of Undetermined Source (RE-SPECT ESUS). Int J Stroke, 10, 1309–12.Google Scholar
Dinicolantonio, JJ, Lavie, CJ, Fares, H, Menezes, AR, O’Keefe, JH, Bangalore, S, et al. (2013). Meta-analysis of cilostazol versus aspirin for the secondary prevention of stroke. Am J Cardiol, 112, 1230–4.Google Scholar
Donadini, MP, Bellesini, M, Squizzato, A. (2018). Aspirin plus clopidogrel vs aspirin alone for preventing cardiovascular events among patients at high risk for cardiovascular events. JAMA, 320, 593–4. doi:10.1001/jama.2018.9641.CrossRefGoogle ScholarPubMed
Eikelboom, JW, Connolly, SJ, Bosch, J, Dagenais, GR, Hart, RG, Shestakovska, O, et al.; COMPASS Investigators. (2017). Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med, 377, 1319–30.Google Scholar
Gotoh, F, Tohgi, H, Hirai, S, Terashi, A, Fukuuchi, Y, Otomo, E, et al. (2000). Cilostazol Stroke Prevention Study: a placebo-controlled double-blind trial for secondary prevention of cerebral infarction. J Stroke Cerebrovasc Dis, 9, 147–57.Google Scholar
Gouya, G, Arrich, J, Wolzt, M, Huber, K, Verheugt, FW, Gurbel, PA, et al. (2014). Antiplatelet treatment for prevention of cerebrovascular events in patients with vascular diseases: a systematic review and meta-analysis. Stroke, 45, 492503.Google Scholar
Halkes, PH, Gray, LJ, Bath, PM, Diener, HC, Guiraud-Chaumeil, B, Yatsu, FM, et al. (2008). Dipyridamole plus aspirin versus aspirin alone in secondary prevention after TIA or stroke: a meta-analysis by risk. J Neurol Neurosurg Psychiatry, 79, 1218–23.Google Scholar
Hankey, GJ, Johnston, SC, Easton, JD, Hacke, W, Mas, JL, Brennan, D, et al.; CHARISMA Trial Investigators. (2011). Effect of clopidogrel plus ASA vs. ASA early after TIA and ischaemic stroke: a substudy of the CHARISMA trial. Int J Stroke, 6, 39.Google Scholar
Hart, RG, Sharma, M, Mundl, H, Kasner, SE, Bangdiwala, SI, Berkowitz, SD, et al.; NAVIGATE ESUS Investigators. (2018) Rivaroxaban for stroke prevention after embolic stroke of undetermined source. N Engl J Med, 378, 21912201.Google Scholar
Hilkens, NA, Algra, A, Kappelle, LJ, Bath, PM, Csiba, L, Rothwell, PM, Greving, JP; CAT Collaboration. (2018a). Early time course of major bleeding on antiplatelet therapy after TIA or ischemic stroke. Neurology, 90, e683–9.Google Scholar
Hilkens, NA, Algra, A, Diener, HC, Reitsma, JB, Bath, PM, Csiba, L, et al.; Cerebrovascular Antiplatelet Trialists’ Collaborative Group. (2017). Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets: S2TOP-BLEED. Neurology, 89, 936–43.Google Scholar
Hilkens, NA, Li, L, Rothwell, PM, Algra, A, Greving, JP. (2018b). External validation of risk scores for major bleeding in a population-based cohort of transient ischemic attack and ischemic stroke patients. Stroke, 49, 601–06.Google Scholar
Huang, WY, Singer, DE, Wu, YL, Chiang, CE, Weng, HH, Lee, M, Ovbiagele, B. (2018). Association of intracranial hemorrhage risk with non-vitamin K antagonist oral anticoagulant use vs aspirin use: a systematic review and meta-analysis. JAMA Neurol, 75(12), 1511–18. doi:10.1001/jamaneurol.2018.2215.Google Scholar
Kamal, AK, Naqvi, I, Husain, MR, Khealani, BA. (2011). Cilostazol versus aspirin for secondary prevention of vascular events after stroke of arterial origin. Cochrane Database Syst Rev, 1. CD008076. doi:10.1002/14651858.CD008076.pub2.Google Scholar
Kim, BJ, Lee, E-J, Kwon, SU, Park, JH, Kim, YJ, Hong, KS, et al. (2018). Prevention of cardiovascular events in Asian patients with ischaemic stroke at high risk of cerebral haemorrhage (PICASSO): a multicentre, randomised controlled trial. Lancet Neurol, 17, 509–18.Google Scholar
Kwok, CS, Shoamanesh, A, Copley, HC, Myint, PK, Loke, YK, Benavente, OR. (2015). Efficacy of antiplatelet therapy in secondary prevention following lacunar stroke: pooled analysis of randomized trials. Stroke, 46, 1014–23.CrossRefGoogle ScholarPubMed
Leonardi-Bee, J, Bath, PM, Bousser, MG, Davalos, A, Diener, HC, Guiraud-Chaumeil, B, et al.; Dipyridamole in Stroke Collaboration (DISC). (2005). Dipyridamole for preventing recurrent ischemic stroke and other vascular events: a meta-analysis of individual patient data from randomized controlled trials. Stroke, 36, 162–8.CrossRefGoogle ScholarPubMed
Markus, HS, Levi, C, King, A, Madigan, J, Norris, J; Cervical Artery Dissection in Stroke Study (CADISS) Investigators. (2019). Antiplatelet therapy vs anticoagulation therapy in cervical artery dissection: the Cervical Artery Dissection in Stroke Study (CADISS) Randomized Clinical Trial Final Results. JAMA Neurol, 76, 657-64.Google Scholar
McDonough, CW, McClure, LA, Mitchell, BD, Gong, Y, Horenstein, RB, Lewis, JP, et al. (2015). CYP2C19 metabolizer status and clopidogrel efficacy in the Secondary Prevention of Small Subcortical Strokes (SPS3) study. JAHA, 4, e001652.Google Scholar
Morrow, DA, Alberts, MJ, Mohr, JP, Ameriso, SF, Bonaca, MP, Goto, S, Hankey, GJ, et al.; Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events–TIMI 50 Steering Committee and Investigators. (2013). Efficacy and safety of vorapaxar in patients with prior ischemic stroke. Stroke, 44, 691–8.Google Scholar
Ogawa, A, Toyoda, K, Kitagawa, K, Kitazono, T, Nagao, T, Yamagami, H, et al. (2019). Comparison of prasugrel and clopidogrel in patients with non-cardioembolic ischaemic stroke: the PRASTRO-I randomised trial. Lancet Neurol, 18, 238–47.Google Scholar
Roe, MT, Armstrong, PW, Fox, KA, White, HD, Prabhakaran, D, Goodman, SG, et al. (2012). Prasugrel versus clopidogrel for acute coronary syndromes without revascularization. N Engl J Med, 367, 1297–309.Google Scholar
Rothwell, PM, Algra, A, Chen, Z, Diener, HC, Norrving, B, Mehta, Z. (2016). Effects of aspirin on risk and severity of early recurrent stroke after transient ischaemic attack and ischaemic stroke: time-course analysis of randomised trials. Lancet, 388, 365–75Google Scholar
Rothwell, PM, Cook, NR, Gaziano, JM, Price, JF, Belch, JFF, Roncaglioni, MC, et al. (2018). Effects of aspirin on risks of vascular events and cancer according to bodyweight and dose: analysis of individual patient data from randomised trials. Lancet, 392, 387–99.CrossRefGoogle ScholarPubMed
Sacco, RL, Diener, H-C, Yusuf, S, Cotton, D, Ounpuu, S, Lawton, WA, et al. (2008). Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. The Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. N Engl J Med, 359, 1238–51.CrossRefGoogle Scholar
Sandercock, PAG, Gibson, LM, Liu, M. (2009). Anticoagulants for preventing recurrence following presumed non-cardioembolic ischaemic stroke or transient ischaemic attack. Cochrane Database Syst Rev, 2. CD000248. doi:10.1002/14651858.CD000248.pub2.CrossRefGoogle ScholarPubMed
Sharma, M, Hart, RG, Connolly, S, Bosch, J, Shestakovska, O, Ng, KH, et al. (2019). Stroke Outcomes in the Cardiovascular OutcoMes for People using Anticoagulation StrategieS (COMPASS) trial. Circulation, 139(9), 1134–45. doi 10.1161/CIRCULATIONAHA.118.035864.Google Scholar
SPS3 Investigators, Benavente, OR, Hart, RG, McClure, LA, Szychowski, JM, Coffey, CS, Pearce, LA. (2012). Effects of clopidogrel added to aspirin in patients with recent lacunar stroke. N Engl J Med, 367, 817–25.Google Scholar
Squizzato, A, Bellesini, M, Takeda, A, Middeldorp, S, Donadini, MP. (2017). Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular events. Cochrane Database Syst Rev, 12. CD005158.Google Scholar
Sudlow, CLM, Mason, G, Maurice, JB, Wedderburn, CJ, Hankey, GJ. (2009). Thienopyridine derivatives versus aspirin for preventing stroke and other serious vascular events in high vascular risk patients. Cochrane Database Syst Rev, 4. CD001246. doi:10.1002/14651858.CD001246.pub2.CrossRefGoogle ScholarPubMed
Topol, EJ, Easton, D, Harrington, RA, Amarenco, P, Califf, RM, Graffagnino, C, et al.; Blockade of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion Trial Investigators. (2003). Randomized, double-blind, placebo-controlled, international trial of the oral IIb/IIIa antagonist lotrafiban in coronary and cerebrovascular disease. Circulation, 108, 399406.Google Scholar
Toyoda, K, Uchiyama, S, Yamaguchi, T, Easton, JD, Kimura, K, Hoshino, H, et al., for the CSPS.com Trial Investigators. (2019). Dual antiplatelet therapy using cilostazol for secondary prevention in high-risk ischaemic stroke: a multicentre randomised controlled trial. Lancet Neurol, 18(6), 539–48.Google Scholar
Wiviott, SD, Braunwald, E, McCabe, CH, Montalescot, G, Ruzyllo, W, Gottlieb, S, et al. (2007). Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med, 357, 2001–15.Google Scholar

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