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  • CLOSURE I Original

    • CLOSURE I

    "Closure or Medical Therapy for Cryptogenic Stroke with Patent Foramen Ovale". The New England Journal of Medicine. ClinicalTrials.gov number, NCT00201461.

    Clinical Question


    Does closure with a percutaneous device reduce the risk of recurrent stroke or TIA in patients with cryptogenic stroke or TIA and patent foramen ovale, compared to medical therapy alone?

    Bottom Line


    In patients with cryptogenic stroke or TIA who also have a patent foramen ovale, closure with a device did not result in a greater benefit than medical therapy alone in preventing recurrent stroke or TIA.

    Major Points




    Guidelines


    At the time of the study, closure of PFO with a percutaneous transcatheter device was an investigational procedure by the FDA. Many patients with cryptogenic stroke and PFO were treated off-label.

    Design


    - Multicenter, randomized, open-label, two-group superiority trial.
    - Participants: 909 patients, aged 18-60, with cryptogenic stroke or TIA and PFO.
    - Interventions: Closure with STARFlex device plus antiplatelet therapy (n=447) vs medical therapy alone (n=462).
    - 2 years of follow-up.
    - Primary outcome: Composite of stroke or TIA, any death within 30 days, or death from neurologic causes between 31 days and 2 years.

    Population


    - Inclusion criteria: Patients 18-60 years, had ischemic stroke or TIA within 6 months, evidence of PFO.
    - Exclusion criteria: Identified potential causes of ischemic stroke or TIA other than PFO.

    Interventions


    - Percutaneous closure of PFO with STARFlex device.
    - Medical therapy treated with warfarin or aspirin or both at investigator's discretion.

    Outcomes


    - Primary outcome (composite of stroke/TIA, death from any cause within 30 days, or death from neurologic causes within 31 days to 2 years): 5.5% in closure group vs 6.8% in medical therapy, adjusted HR 0.78 (95% CI, 0.45 to 1.35; P=0.37).
    - Stroke: 2.9% closure group vs 3.1% medical therapy (P=0.79).
    - TIA: 3.1% closure group vs 4.1% medical therapy (P=0.44).
    - No significant differences in rates of other serious adverse events.

    Criticisms


    - Did not have power to detect small reductions in event rates.
    - The results do not preclude a role for PFO closure in highly selected patient groups.
    - Increased rate of atrial fibrillation in the closure group.
    - Periprocedural major vascular complications occurred only in the closure group (3.2%).

    Funding


    NMT Medical, Boston (sponsor of the trial).

    Further Reading


    The full text of this article is available at NEJM.org and detailed inclusion/exclusion criteria, definitions of major end points, and more information about the supplementary results can be found in the Supplementary Appendix linked in the original full text.