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  • Review Article
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Antithrombotics for secondary prevention of noncardioembolic ischaemic stroke

Nature Reviews Neurology volume 8, pages 223–235 (2012)Cite this article

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Abstract

Antiplatelet therapy is more effective than anticoagulation for the prevention of noncardioembolic ischaemic stroke. The choice of antiplatelet regimen, however, remains contentious. Recent controversies regarding aspirin resistance and the optimal dosing of aspirin, as well as recognition of the variable bioactivation of clopidogrel, have added further confusion to the debate. The American Heart Association (AHA) and American Stroke Association (ASA) recently released their third joint guideline in the past 5 years on secondary stroke prevention. The European Stroke Organisation has published three guidelines on this issue since 2000. These frequent updates have been necessary because of rapidly accumulating data from clinical trials. Careful consideration of the sometimes confusing trial results reveals that the 2011 AHA–ASA guidelines are correct in no longer specifying a 'preferred' antiplatelet regimen from among the choices recently studied. This recommendation does not, however, mean that all antiplatelet regimens should be considered equal. This Review discusses the various antiplatelet regimens, and the trials that led to the rapid evolution of the guidelines for secondary prevention of ischaemic stroke.

Key Points

  • Numerous organization-specific guidelines and frequent guideline updates have made the selection of appropriate antithrombotic therapy for secondary prevention of noncardioembolic ischaemic stroke challenging

  • Aspirin, with strong efficacy data, good tolerability and low cost, is recommended as first-line therapy at a dose of 81–162 mg/day

  • Trials directly comparing clopidogrel with aspirin for secondary stroke prevention are lacking, but clopidogrel is considered an acceptable alternative for patients who cannot take aspirin or have experienced a cerebrovascular event while taking aspirin

  • Evidence supports the superiority of extended-release dipyridamole plus aspirin over aspirin monotherapy, but tolerability issues and compliance limit use of this agent in clinical practice

  • Dual antiplatelet therapy with clopidogrel and aspirin, and adjusted-dose anticoagulation do not provide benefit compared with aspirin monotherapy and are associated with harmful outcomes

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Figure 1: Overview of platelet activation and inhibition by endogenous mediators and antiplatelet therapies.
Figure 2: Results of a meta-analysis evaluating the effect of combination therapy comprising aspirin plus either immediate-release dipyridamole or extended-release dipyridamole on occurrence of nonfatal stroke.
Figure 3: Thienopyridine versus aspirin for secondary prevention of all-cause stroke.
Figure 4: Dipyridamole: an incompletely understood drug.

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Authors and Affiliations

  1. Oregon Health and Science University Hospital, 3181 SW Sam Jackson Road, Portland, 97239, OR, USA

    Bruce A. Warden & Craig D. Williams

  2. Oregon State University/Oregon Health and Science University College of Pharmacy, 3303 SW Bond Avenue, CH12C, Portland, 97239, OR, USA

    Alana M. Willman

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All authors contributed to researching data for the article and discussion of the article content. B. A. Warden and C. D. Williams wrote the article. All authors contributed to review and/or editing of the manuscript before submission.

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Correspondence to Craig D. Williams.

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Supplementary information

Supplementary Table 1

Trials of non-aspirin antiplatelet therapies for secondary stroke prevention (DOC 57 kb)

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Warden, B., Willman, A. & Williams, C. Antithrombotics for secondary prevention of noncardioembolic ischaemic stroke. Nat Rev Neurol 8, 223–235 (2012). https://doi.org/10.1038/nrneurol.2012.33

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