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

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Abstract

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.

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Acknowledgements

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

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Authors and Affiliations

  1. Department of Internal Medicine, Hurley Medical Center/Michigan State University, Flint, MI, 48503, USA

    Babikir Kheiri, Tarek Haykal, Bakr Swaid, Adam Chahine & Ghassan Bachuwa

  2. Division of Cardiology, West Virginia University School of Medicine, Morgantown, WV, 26506, USA

    Mohammed Osman

  3. Division of Hematology & Oncology, Ascension St. John Hospital, Grosse Pointe Woods, MI, 48236, USA

    Ahmed Abdalla

  4. Research Assistance, Flint, MI, 48503, USA

    Sahar Ahmed

  5. Division of Cardiology, Hurley Medical Center/Michigan State University, Flint, MI, 48503, USA

    Mustafa Hassan

  6. Division of Neurology, Hurley Medical Center/Michigan State University, Flint, MI, 48503, USA

    Mohammed Al Qasmi

  7. Brigham and Women’s Hospital Heart & Vascular Center, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA

    Deepak L. Bhatt

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  1. Babikir Kheiri
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Correspondence to Deepak L. Bhatt.

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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, ACC.org; 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.

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Kheiri, B., Osman, M., Abdalla, A. et al. Clopidogrel and aspirin after ischemic stroke or transient ischemic attack: an updated systematic review and meta-analysis of randomized clinical trials. J Thromb Thrombolysis 47, 233–247 (2019). https://doi.org/10.1007/s11239-018-1786-z

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