Long-Term Outcomes of Patent Foramen Ovale Closure or Medical Therapy after Stroke

Jeffrey L Saver, John D Carroll, David E Thaler, Richard W Smalling, Lee A MacDonald, David S Marks, David L Tirschwell, RESPECT Investigators, Giovanni Bernardini

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Whether closure of a patent foramen ovale reduces the risk of recurrence of ischemic stroke in patients who have had a cryptogenic ischemic stroke is unknown.

METHODS: In a multicenter, randomized, open-label trial, with blinded adjudication of end-point events, we randomly assigned patients 18 to 60 years of age who had a patent foramen ovale (PFO) and had had a cryptogenic ischemic stroke to undergo closure of the PFO (PFO closure group) or to receive medical therapy alone (aspirin, warfarin, clopidogrel, or aspirin combined with extended-release dipyridamole; medical-therapy group). The primary efficacy end point was a composite of recurrent nonfatal ischemic stroke, fatal ischemic stroke, or early death after randomization. The results of the analysis of the primary outcome from the original trial period have been reported previously; the current analysis of data from the extended follow-up period was considered to be exploratory.

RESULTS: We enrolled 980 patients (mean age, 45.9 years) at 69 sites. Patients were followed for a median of 5.9 years. Treatment exposure in the two groups was unequal (3141 patient-years in the PFO closure group vs. 2669 patient-years in the medical-therapy group), owing to a higher dropout rate in the medical-therapy group. In the intention-to-treat population, recurrent ischemic stroke occurred in 18 patients in the PFO closure group and in 28 patients in the medical-therapy group, resulting in rates of 0.58 events per 100 patient-years and 1.07 events per 100 patient-years, respectively (hazard ratio with PFO closure vs. medical therapy, 0.55; 95% confidence interval [CI], 0.31 to 0.999; P=0.046 by the log-rank test). Recurrent ischemic stroke of undetermined cause occurred in 10 patients in the PFO closure group and in 23 patients in the medical-therapy group (hazard ratio, 0.38; 95% CI, 0.18 to 0.79; P=0.007). Venous thromboembolism (which comprised events of pulmonary embolism and deep-vein thrombosis) was more common in the PFO closure group than in the medical-therapy group.

CONCLUSIONS: Among adults who had had a cryptogenic ischemic stroke, closure of a PFO was associated with a lower rate of recurrent ischemic strokes than medical therapy alone during extended follow-up. (Funded by St. Jude Medical; RESPECT ClinicalTrials.gov number, NCT00465270 .).

Original languageEnglish
Pages (from-to)1022-1032
Number of pages11
JournalNew England Journal of Medicine
Volume377
Issue number11
DOIs
Publication statusPublished - Sep 14 2017

Keywords

  • Adolescent
  • Adult
  • Anticoagulants
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Foramen Ovale, Patent
  • Humans
  • Intention to Treat Analysis
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors
  • Recurrence
  • Secondary Prevention
  • Septal Occluder Device
  • Single-Blind Method
  • Stroke
  • Venous Thromboembolism
  • Young Adult
  • Comparative Study
  • Journal Article
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

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  • Cite this

    Saver, J. L., Carroll, J. D., Thaler, D. E., Smalling, R. W., MacDonald, L. A., Marks, D. S., Tirschwell, D. L., RESPECT Investigators, & Bernardini, G. (2017). Long-Term Outcomes of Patent Foramen Ovale Closure or Medical Therapy after Stroke. New England Journal of Medicine, 377(11), 1022-1032. https://doi.org/10.1056/NEJMoa1610057