Medicine by the Numbers

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Antiplatelet Agents for Preventing Early Recurrence of Ischemic Stroke or TIA


Am Fam Physician. 2021 Mar 1;103(5):online.


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1 in 40 had a reduced stroke recurrence

1 in 91 had a major extracranial hemorrhage

2.5% reduction in stroke recurrence

1.1% increase in major extracranial hemorrhage

TIA = transient ischemic attack.



1 in 40 had a reduced stroke recurrence

1 in 91 had a major extracranial hemorrhage

2.5% reduction in stroke recurrence

1.1% increase in major extracranial hemorrhage

TIA = transient ischemic attack.

Details for This Review

Study Population: Five randomized controlled trials including a total of 10,739 patients with atherothrombotic ischemic stroke or transient ischemic attack (TIA)

Efficacy End Points: Stroke recurrence and vascular death; secondary outcomes included myocardial infarction, vascular death, and death from all causes

Harm End Points: Intracranial or extracranial hemorrhage

Narrative: Ischemic strokes range in severity from minor to debilitating. Minor strokes and TIAs may be followed by recurrent strokes, with the highest risk in the first 48 hours.1 Approximately 30% of strokes are recurrent.2 Antiplatelet agents may reduce the risk of recurrence and prevent disability, but they may also increase the risk of hemorrhage.24 This Cochrane review updates a previous review examining the effect of adding clopidogrel (Plavix) to aspirin therapy after atherothrombotic acute ischemic stroke or TIA.

This Cochrane review included randomized controlled trials evaluating patients taking any combination of multiple antiplatelet agents vs. a single agent within 72 hours of an atherothrombotic acute ischemic stroke or TIA.5 The primary outcome was stroke recurrence during at least three months of follow-up. Secondary outcomes included myocardial infarction, intracranial hemorrhage, extracranial hemorrhage, and death. When there was more than one follow-up period, the authors included outcomes at one week, one month, three months, and six months.

The meta-analysis included five randomized controlled trials with 10,739 patients that compared aspirin plus clopidogrel vs. aspirin alone.3,69 All medications were administered orally, and most used a loading dose of clopidogrel, 300 mg. Dosing of aspirin ranged from 75 mg to 300 mg. Follow-up ranged from 30 days to one year.

Dual antiplatelet therapy with aspirin plus clopidogrel was associated with less risk of recurrent stroke compared with aspirin alone (6.5%

Author disclosure: No relevant financial affiliations.

Copyright © 2021 MD Aware, LLC ( Used with permission.

This series is coordinated by Christopher W. Bunt, MD, AFP assistant medical editor, and Daniel Runde, MD, from the NNT Group.

A collection of Medicine by the Numbers published in AFP is available at


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4. 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 [published correction appears in Stroke. 2019;50(12):e440–e441]. Stroke. 2019;50(12):e344–e418.

5. Naqvi IA, Kamal AK, Rehman H. Multiple versus fewer antiplatelet agents for preventing early recurrence after ischaemic stroke or transient ischaemic attack. Cochrane Database Syst Rev. 2020;(8):CD009716.

6. Johnston SC, Easton JD, Farrant M, et al.; Clinical Research Collaboration; Neurological Emergencies Treatment Trials Network, and the POINT Investigators. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med. 2018;379(3):215–225.

7. Hankey GJ, Johnston SC, Easton JD, et al.; CHARISMA trial investigators. Effect of clopidogrel plus ASA vs. ASA early after TIA and ischaemic stroke: a substudy of the CHARISMA trial. Int J Stroke. 2011;6(1):3–9.

8. Kennedy J, Hill MD, Ryckborst KJ, et al.; FASTER Investigators. Fast assessment of stroke and transient ischaemic attack to prevent early recurrence (FASTER): a randomised controlled pilot trial. Lancet Neurol. 2007;6(11):961–969.

9. Petrovska-Cvetkovska D, Baneva N, Trencev R, et al. Efficacy and tolerability of aspirin, aspirin plus clopidogrel and statins in prevention after transient ischemic attacks. Int J Stroke. 2008;3(suppl 1):314 (Abst.PO02–192).



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