Archive for the ‘Patent foramen ovale closure’ Category

Journal Club 3 April 2013


Paper 1

Closure of Patent Foramen Ovale versus Medical Therapy after Cryptogenic Stroke



Summary 1


Whether closure of a patent foramen ovale is effective in the prevention of recurrent
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.


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.


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.


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.

Paper 2

Percutaneous Closure of Patent Foramen Ovale in Cryptogenic Embolism





The options for secondary prevention of cryptogenic embolism in patients with patent
foramen ovale are administration of antithrombotic medications or percutaneous
closure of the patent foramen ovale. We investigated whether closure is superior to
medical therapy.


We performed a multicenter, superiority trial in 29 centers in Europe, Canada, Brazil,
and Australia in which the assessors of end points were unaware of the study-group
assignments. Patients with a patent foramen ovale and ischemic
stroke, transient
attack (TIA), or a peripheral thromboembolic event were randomly assigned
to undergo closure of the patent foramen ovale with the Amplatzer PFO
Occluder or to receive medical therapy. The primary end point was a composite of
death, nonfatal stroke, TIA, or peripheral embolism. Analysis was performed on data
for the intention-to-treat population.


The mean duration of follow-up was 4.1 years in the closure group and 4.0 years in
the medical-therapy group. The primary end point occurred in 7 of the 204 patients
(3.4%) in the closure group and in 11 of the 210 patients (5.2%) in the medicaltherapy
group (hazard ratio for closure vs. medical therapy, 0.63; 95% confidence
interval [CI], 0.24 to 1.62; P = 0.34). Nonfatal stroke occurred in 1 patient (0.5%) in the
closure group and 5 patients (2.4%) in the medical-therapy group (hazard ratio, 0.20;
95% CI, 0.02 to 1.72; P = 0.14), and TIA occurred in 5 patients (2.5%) and 7 patients
(3.3%), respectively (hazard ratio, 0.71; 95% CI, 0.23 to 2.24; P = 0.56).


Closure of a patent foramen ovale for secondary prevention of cryptogenic embolism
did not result in a significant reduction in the risk of recurrent embolic events or
death as compared with medical therapy.


Journal Club 31 October 2012


None. TCT presentations on PFO Closure Trials




Comprehensive presentation: PFO/ASD talk (also listed on Education Session page).

Journal club 11 April 2012


Closure or Medical Therapy for Cryptogenic Stroke with Patent Foramen Ovale





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


StarFlex PFO closure device


Medical therapy: aspirin alone, warfarin alone, aspirin and warfarin (at discretion of investigator)


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
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.

Discussion Summary 

  • This was a negative trial.
  • The issues of being under-powered.
  • The high frequency of alternative explanations for stroke were noted/
  • The increased frequency of atrial fibrillation in the device group compared with medical therapy and the transesophageal echocardiographic’device associated thrombus’ are concerning and suggest that medical therapy is in general the preferred initial strategy.



See also previous post.