Journal of Thrombosis and Thrombolysis

, Volume 47, Issue 2, pp 233–247 | Cite as

Clopidogrel and aspirin after ischemic stroke or transient ischemic attack: an updated systematic review and meta-analysis of randomized clinical trials

  • Babikir Kheiri
  • Mohammed Osman
  • Ahmed Abdalla
  • Tarek Haykal
  • Bakr Swaid
  • Sahar Ahmed
  • Adam Chahine
  • Mustafa Hassan
  • Ghassan Bachuwa
  • Mohammed Al Qasmi
  • Deepak L. BhattEmail author


Recurrent stroke is common immediately following a transient ischemic attack (TIA) or ischemic stroke. Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin may provide greater protection against subsequent stroke than monotherapy. Electronic databases were searched for randomized clinical trials (RCTs) comparing DAPT with monotherapy in ischemic stroke/TIA. Sixteen RCTs with a total of 29,032 patients were included. Compared with monotherapy, DAPT was associated with significantly lower rates of any stroke (risk ratio [RR] 0.80; 95% confidence interval [CI] 0.72–0.89) and ischemic stroke (RR 0.75; 95% CI 0.66–0.85) during any follow-up period. Although significant increases in intracranial bleeding (RR 1.55; 95% CI 1.20–2.01) and major bleeding (RR 1.90; 95% CI 1.33–2.72) were associated with DAPT, especially with long-term follow-up, the number needed to harm was 258 and 113, respectively. Nevertheless, short-duration DAPT (≤ 1 month) started during the early acute ischemic phase was associated with less bleeding than longer DAPT and greater reduction of recurrent strokes compared with monotherapy. In contrast, long DAPT and DAPT started later after the index event (≥ 1 month) were associated with similar rates of any stroke and increased risks of bleeding compared with monotherapy. Other clinical outcomes were essentially similar between the two groups and included recurrent TIA (RR 0.88; 95% CI 0.72–1.07), myocardial infarction (RR 1.04; 95% CI 0.84–1.29), vascular death (RR 0.99; 95% CI 0.82–1.19), and any death (RR 1.12; 95% CI 0.88–1.42). Similar findings were observed in patients who presented with minor stroke/TIA. Conclusions: Among patients who presented with ischemic stroke/TIA, short-course clopidogrel plus aspirin immediately following the index event appears to be more effective than and as safe as monotherapy for secondary stroke prevention.


Clopidogrel Aspirin DAPT Ischemic stroke Acute stroke TIA Meta-analysis 



We would like to thank Katherine Negele, editorial assistant, research department, Hurley Medical Center, for assistance with manuscript editing.

Compliance with ethical standards

Conflict of interest

Dr. Mustafa Hassan has received a research grant from Abbott. Dr. Mohammed Al Qasmi is on speaker bureau for Genentech. Dr. Deepak L. Bhatt discloses the following relationships - Advisory Board: Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care; Chair: American Heart Association Quality Oversight Committee; Data Monitoring Committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic, Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine, Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News,; Vice-Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Abbott, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Idorsia, Ironwood, Ischemix, Lilly, Medtronic, PhaseBio, Pfizer, Regeneron, Roche, Sanofi Aventis, Synaptic, The Medicines Company; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); Site Co-Investigator: Biotronik, Boston Scientific, St. Jude Medical (now Abbott), Svelte; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Merck, Novo Nordisk, PLx Pharma, Takeda. The remaining authors report no relationships that could be construed as a conflict of interest.

Supplementary material

11239_2018_1786_MOESM1_ESM.docx (237 kb)
Supplementary material 1 (DOCX 236 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Babikir Kheiri
    • 1
  • Mohammed Osman
    • 2
  • Ahmed Abdalla
    • 3
  • Tarek Haykal
    • 1
  • Bakr Swaid
    • 1
  • Sahar Ahmed
    • 4
  • Adam Chahine
    • 1
  • Mustafa Hassan
    • 5
  • Ghassan Bachuwa
    • 1
  • Mohammed Al Qasmi
    • 6
  • Deepak L. Bhatt
    • 7
    Email author
  1. 1.Department of Internal MedicineHurley Medical Center/Michigan State UniversityFlintUSA
  2. 2.Division of CardiologyWest Virginia University School of MedicineMorgantownUSA
  3. 3.Division of Hematology & OncologyAscension St. John HospitalGrosse Pointe WoodsUSA
  4. 4.Research AssistanceFlintUSA
  5. 5.Division of CardiologyHurley Medical Center/Michigan State UniversityFlintUSA
  6. 6.Division of NeurologyHurley Medical Center/Michigan State UniversityFlintUSA
  7. 7.Brigham and Women’s Hospital Heart & Vascular CenterHarvard Medical SchoolBostonUSA

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