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Contemporary Antiplatelet and Anticoagulant Therapies for Secondary Stroke Prevention: A Narrative Review of Current Literature and Guidelines

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Abstract

Purpose of Review

Stroke is a leading cause of death and disability worldwide. The annual incidence of new or recurrent stroke is approximately 795,000 cases per year in the United States, of which 87% are ischemic in nature. In addition to the management of modifiable high-risk factors to reduce the risk of recurrent stroke, antithrombotic agents (antiplatelets and anticoagulants) play an important role in secondary stroke prevention. This review will discuss the published literature on the use of antiplatelets and anticoagulants in secondary prevention of acute ischemic stroke and transient ischemic attack (TIA), including their pharmacology, efficacy, and adverse effects. We will also highlight the role of dual antiplatelet therapy (DAPT) in secondary stroke prevention, along with supporting literature.

Recent Findings

Single antiplatelet therapy (SAPT) with aspirin or clopidogrel reduces the risk of recurrent ischemic stroke in patients with non-cardioembolic ischemic stroke or TIA. However, as shown in recent trials, short-term DAPT with aspirin and clopidogrel or ticagrelor for 21–30 days is more effective than SAPT in patients with minor acute non-cardioembolic stroke or high-risk TIA. Although short-term DAPT is highly effective in preventing recurrent stroke, a more prolonged course can increase bleeding risks without additional benefit. DAPT for 90 days, followed by aspirin monotherapy for patients with large vessel intracranial atherosclerotic disease, is suitable for secondary stroke prevention. However, patients need to be monitored for both minor (e.g., bruising) and major (e.g., intracranial) bleeding complications. Conversely, oral warfarin and newer direct oral anticoagulant (DOACs) such as dabigatran, rivaroxaban, apixaban, and edoxaban are the agents of choice for secondary stroke prevention in patients with non-valvular cardioembolic strokes. DOACs may be preferred over warfarin due to decreased bleeding risks, including ICH, lack of need for international normalized ratio monitoring, no dietary restrictions, and limited drug-drug interactions.

Summary

The choice between different antiplatelets and anticoagulants for prevention of ischemic stroke depends on the underlying stroke mechanism, cytochrome P450 2C19 polymorphisms, bleeding risk profile, compliance, drug tolerance, and drug resistance. Physicians must carefully weigh each patient's relative benefits and bleeding risks before initiating an antiplatelet/anticoagulant treatment regimen. Further studies are warranted to study the optimal duration of DAPT in symptomatic intracranial atherosclerosis since the benefit is most pronounced in the short term while the bleeding risk remains high during the extended duration of therapy.

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Authors and Affiliations

  1. Department of Neurology, University of Mississippi Medical Center, Jackson, MS, USA

    Kunal Bhatia, Lindsey M. Ladd & Kelsey H. Carr

  2. Neurological Service, SS Annunziata Hospital, Sulmona, L’Aquila, Italy

    Mario Di Napoli

  3. Department of Neurology, Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA

    Jeffrey L. Saver

  4. Department of Neurology, McGovern Medical School, University of Texas Health Sciences Center, Houston, TX, USA

    Louise D. McCullough

  5. Department of Neurology, University of New Mexico, Albuquerque, NM, USA

    Maryam Hosseini Farahabadi, Sara Y. Sabbagh & Afshin A. Divani

  6. Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, USA

    Diana L. Alsbrook

  7. Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Archana Hinduja

  8. Department of Neurology, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Jorge G. Ortiz Garcia

  9. Department of Neurology, Tufts Medical Center, Boston, MA, USA

    Alibay Jafarli

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Kunal Bhatia, Lindsey M. Ladd, Kelsey H. Carr, Mario Di Napoli, Jeffrey L. Saver, Louise D McCullough, Maryam Hosseini Farahabadi, Diana L. Alsbrook, Archana Hinduja, Jorge G. Ortiz Garcia, Sara Y. Sabbagh, Alibay Jafarli, and Afshin A. Divani each declare no potential conflicts of interest.

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Bhatia, K., Ladd, L.M., Carr, K.H. et al. Contemporary Antiplatelet and Anticoagulant Therapies for Secondary Stroke Prevention: A Narrative Review of Current Literature and Guidelines. Curr Neurol Neurosci Rep 23, 235–262 (2023). https://doi.org/10.1007/s11910-023-01266-2

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