Closure or medical therapy for cryptogenic stroke with patent foramen ovale

N Engl J Med. 2012 Mar 15;366(11):991-9. doi: 10.1056/NEJMoa1009639.

Abstract

Background: The prevalence of patent foramen ovale among patients with cryptogenic stroke is higher than that in the general population. Closure with a percutaneous device is often recommended in such patients, but it is not known whether this intervention reduces the risk of recurrent stroke.

Methods: We conducted a multicenter, randomized, open-label trial of closure with a percutaneous device, as compared with medical therapy alone, in patients between 18 and 60 years of age who presented with a cryptogenic stroke or transient ischemic attack (TIA) and had a patent foramen ovale. The primary end point was a composite of stroke or transient ischemic attack during 2 years of follow-up, death from any cause during the first 30 days, or death from neurologic causes between 31 days and 2 years.

Results: A total of 909 patients were enrolled in the trial. The cumulative incidence (Kaplan-Meier estimate) of the primary end point was 5.5% in the closure group (447 patients) as compared with 6.8% in the medical-therapy group (462 patients) (adjusted hazard ratio, 0.78; 95% confidence interval, 0.45 to 1.35; P=0.37). The respective rates were 2.9% and 3.1% for stroke (P=0.79) and 3.1% and 4.1% for TIA (P=0.44). No deaths occurred by 30 days in either group, and there were no deaths from neurologic causes during the 2-year follow-up period. A cause other than paradoxical embolism was usually apparent in patients with recurrent neurologic events.

Conclusions: In patients with cryptogenic stroke or TIA who had a patent foramen ovale, closure with a device did not offer a greater benefit than medical therapy alone for the prevention of recurrent stroke or TIA. (Funded by NMT Medical; ClinicalTrials.gov number, NCT00201461.).

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use
  • Aspirin / therapeutic use
  • Clopidogrel
  • Combined Modality Therapy
  • Drug Therapy, Combination
  • Embolism, Paradoxical / prevention & control*
  • Female
  • Foramen Ovale, Patent / complications
  • Foramen Ovale, Patent / drug therapy*
  • Foramen Ovale, Patent / surgery*
  • Humans
  • Ischemic Attack, Transient / etiology
  • Ischemic Attack, Transient / prevention & control*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Postoperative Complications
  • Prostheses and Implants
  • Secondary Prevention
  • Stroke / etiology
  • Stroke / prevention & control*
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / therapeutic use
  • Warfarin / adverse effects
  • Warfarin / therapeutic use
  • Young Adult

Substances

  • Anticoagulants
  • Platelet Aggregation Inhibitors
  • Warfarin
  • Clopidogrel
  • Ticlopidine
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT00201461