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  • SPS3 Clopidogrel-ASA Original

    • SPS3 Clopidogrel-ASA

    "Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack".
    The New England Journal of Medicine. 2021. 385(1):35-43.
    PubMed•Full text•PDF

    Contents


    1 Clinical Question
    2 Bottom Line
    3 Major Points
    4 Guidelines
    5 Design
    6 Population
    6.1 Inclusion Criteria
    6.2 Exclusion Criteria
    6.3 Baseline Characteristics
    7 Interventions
    8 Outcomes
    8.1 Primary Outcomes
    8.2 Secondary Outcome
    9 Criticisms
    10 Funding
    11 Further Reading

    Clinical Question


    In patients with recent symptomatic lacunar infarcts, does the addition of clopidogrel to aspirin improve outcomes compared to aspirin alone?

    Bottom Line


    Among patients with recent symptomatic lacunar infarcts, the addition of clopidogrel to aspirin did not significantly reduce the risk of recurrent stroke and significantly increased the risk of bleeding and death.

    Major Points


    Lacunar infarcts are a type of stroke caused by cerebral small-vessel disease. The Secondary Prevention of Small Subcortical Strokes (SPS3) trial evaluated whether clopidogrel in combination with aspirin is superior to aspirin alone for secondary stroke prevention in a cohort of patients with MRI-confirmed recent lacunar strokes.

    Guidelines


    Current guidelines do not recommend the addition of clopidogrel to aspirin for the secondary prevention of lacunar stroke based on the results of the SPS3 trial.

    Design


    - Double-blind, multicenter trial
    - N=3020 patients with lacunar infarcts on MRI
    - Randomization to clopidogrel (75 mg daily) plus aspirin (325 mg daily) or placebo plus aspirin
    - Mean follow-up of 3.4 years
    - Analysis: Intention-to-treat
    - Funding: National Institute of Neurological Disorders and Stroke, with study medication donations from Sanofi-Aventis and Bristol-Myers Squibb

    Population


    - Inclusion Criteria: Patients aged ≥30 years old, symptomatic lacunar stroke within the preceding 180 days, no major risk factors for cardioembolic stroke, and met MRI criteria for recent lacunar infarct
    - Exclusion Criteria: Disabling stroke (modified Rankin score ≥4), previous intracerebral hemorrhage or cortical ischemic stroke, microbleeding on MRI
    - Baseline Characteristics: Mean age 63 years, 63% men, 75% history of hypertension, 37% diabetes, 20% current smokers

    Interventions


    - Patients received 325 mg of enteric-coated aspirin daily and were randomized to receive 75 mg of clopidogrel daily or a matching placebo.

    Outcomes


    - Primary Outcomes: Recurrent stroke (ischemic or hemorrhagic)
    - Secondary Outcome: Major extracranial hemorrhage, death

    Criticisms


    - The observed benefit of dual antiplatelet therapy was not seen in the specific patient population with lacunar stroke.
    - The dose of aspirin (325 mg daily) was higher than in some other trials, although not likely a factor affecting outcomes.

    Funding


    - The trial was supported by a grant from the National Institute of Neurological Disorders and Stroke and medication donations from Sanofi-Aventis and Bristol-Myers Squibb.

    Further Reading


    The members of the SPS3 trial investigators are listed in the Supplementary Appendix available at NEJM.org. The original publication of the trial results can be found in the New England Journal of Medicine.