Faculty Collaboration Database

Closure of patent foramen ovale versus medical therapy after cryptogenic stroke. N Engl J Med 2013 Mar 21;368(12):1092-100

Date

03/22/2013

Pubmed ID

23514286

DOI

10.1056/NEJMoa1301440

Abstract

BACKGROUND: Whether closure of a patent foramen ovale is effective in the prevention of recurrent ischemic stroke in patients who have had a cryptogenic stroke is unknown. We conducted a trial to evaluate whether closure is superior to medical therapy alone in preventing recurrent ischemic stroke or early death in patients 18 to 60 years of age.

METHODS: In this prospective, multicenter, randomized, event-driven trial, we randomly assigned patients, in a 1:1 ratio, to medical therapy alone or closure of the patent foramen ovale. The primary results of the trial were analyzed when the target of 25 primary end-point events had been observed and adjudicated.

RESULTS: We enrolled 980 patients (mean age, 45.9 years) at 69 sites. The medical-therapy group received one or more antiplatelet medications (74.8%) or warfarin (25.2%). Treatment exposure between the two groups was unequal (1375 patient-years in the closure group vs. 1184 patient-years in the medical-therapy group, P=0.009) owing to a higher dropout rate in the medical-therapy group. In the intention-to-treat cohort, 9 patients in the closure group and 16 in the medical-therapy group had a recurrence of stroke (hazard ratio with closure, 0.49; 95% confidence interval [CI], 0.22 to 1.11; P=0.08). The between-group difference in the rate of recurrent stroke was significant in the prespecified per-protocol cohort (6 events in the closure group vs. 14 events in the medical-therapy group; hazard ratio, 0.37; 95% CI, 0.14 to 0.96; P=0.03) and in the as-treated cohort (5 events vs. 16 events; hazard ratio, 0.27; 95% CI, 0.10 to 0.75; P=0.007). Serious adverse events occurred in 23.0% of the patients in the closure group and in 21.6% in the medical-therapy group (P=0.65). Procedure-related or device-related serious adverse events occurred in 21 of 499 patients in the closure group (4.2%), but the rate of atrial fibrillation or device thrombus was not increased.

CONCLUSIONS: In the primary intention-to-treat analysis, there was no significant benefit associated with closure of a patent foramen ovale in adults who had had a cryptogenic ischemic stroke. However, closure was superior to medical therapy alone in the prespecified per-protocol and as-treated analyses, with a low rate of associated risks. (Funded by St. Jude Medical; RESPECT ClinicalTrials.gov number, NCT00465270.).

Author List

Carroll JD, Saver JL, Thaler DE, Smalling RW, Berry S, MacDonald LA, Marks DS, Tirschwell DL, RESPECT Investigators

Authors

Diane S. Book MD Associate Professor in the Neurology department at Medical College of Wisconsin
David S. Marks MD Vice Chair, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Cardiac Catheterization
Embolism
Female
Fibrinolytic Agents
Follow-Up Studies
Foramen Ovale, Patent
Humans
Intention to Treat Analysis
Male
Middle Aged
Proportional Hazards Models
Prospective Studies
Risk
Secondary Prevention
Septal Occluder Device
Single-Blind Method
Stroke
Treatment Outcome