Patent Foramen Ovale Closure or Antiplatelet Therapy for Cryptogenic Stroke - REDUCE PFO

Sep 18, 2017
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Gore Medical
Date Published:
09/13/2017
Date Updated:
09/18/2017
Original Posted Date:
09/18/2017
References

Contribution To Literature:

The REDUCE trial showed that PFO closure with the Gore Septal Occluder was superior to medical management in reducing recurrent strokes.

Description:

Numerous observational studies have suggested a beneficial effect of patent foramen ovale (PFO) closure on recurrent stroke in patients with cryptogenic stroke and PFO. However, clinical trial data on this topic have been limited. The REDUCE trial sought to compare outcomes after PFO closure with the Amplatzer PFO Occluder over medical therapy in patients with cryptogenic stroke and evidence of a PFO.

Study Design

All patients had cryptogenic stroke/transient ischemic attack (TIA) (90% had stroke). Patients were randomly assigned in a 2:1 ratio to undergo PFO closure plus antiplatelet therapy (PFO closure group; n = 441) or to receive antiplatelet therapy alone (antiplatelet only group; n = 223). PFO closure was performed with either the Helex Septal Occluder (implanted through late 2012) or the Cardioform Septal Occluder (implanted from late 2012 onward). All patients received antiplatelet therapy.  

  • Total number of enrollees: 664
  • Duration of follow-up: 3.2 years (median)
  • Mean patient age: 45 years
  • Percentage female: 40%
  • Percentage diagnosed with diabetes mellitus: 4%

Inclusion criteria:

  • Age 18-59 years
  • Cryptogenic ischemic stroke within 180 days before randomization
  • PFO with a right-to-left shunt

Exclusion criteria:

  • Stenosis of 50% or more of the diameter of a major vessel or with occlusion of a major vessel
  • Stroke as a result of small-vessel occlusive disease, defined as the presence of a small, deep infarction (<1.5 cm in diameter) or a typical clinical lacunar syndrome
  • Uncontrolled diabetes mellitus
  • Uncontrolled hypertension
  • Autoimmune disease
  • Recent history of alcohol or drug abuse
  • Specific indication for anticoagulation

Other salient features/characteristics:

  • Moderate to severe PFO shunt size: 82%
  • Previous stroke: 12%

Principal Findings:

Co-primary endpoints for PFO closure vs. medical management, respectively:

  • Recurrent clinical ischemic stroke: 1.4% vs. 5.4%, hazard ratio 0.23, 95% confidence interval [CI] 0.09-0.62; p = 0.002
  • New brain infarction (clinical ischemic stroke or silent brain infarction): 5.7% vs. 11.3%, relative risk 0.51, 95% CI 0.29-0.91, p = 0.04

Secondary outcomes for PFO closure vs. medical management:

  • Device-related serious adverse events (SAE): 1.4%
  • Procedure-related SAE: 2.5%
  • Death: 0.5% vs. 0%
  • Serious bleeding: 1.8% vs. 2.7%
  • Any atrial fibrillation or flutter: 6.6% vs. 0.4%

Interpretation:

The results of the REDUCE trial indicate that PFO closure with the Gore Septal Occluder is superior to medical management in reducing recurrent strokes in patients with presumed cryptogenic stroke and evidence of a PFO on 24-month follow-up. This is a landmark trial and will likely change practice paradigms for the management of cryptogenic stroke.

Based on the extended follow-up duration of the RESPECT trial, the US Food and Drug Administration (FDA) approved the use of the Amplatzer PFO occluder in patients between ages 18-60 years with a cryptogenic stroke. A strong collaboration between neurologists and cardiologists to exclude other causes of strokes also was emphasized in the FDA statement. If approved, the Gore PFO device will be a welcome addition to the interventional armamentarium for this condition. It is unclear if certain PFO anatomies/conditions may lend themselves better to one device versus the other.  

References:

Søndergaard L, Kasner SE, Rhodes JF, et al., on behalf of the Gore REDUCE Clinical Study Investigators. Patent Foramen Ovale Closure or Antiplatelet Therapy for Cryptogenic Stroke. N Engl J Med 2017;377:1033-42.

Editorial: Ropper AH. Tipping Point for Patent Foramen Ovale Closure. N Engl J Med 2017;377:1093-5.

Keywords: Atrial Fibrillation, Brain Infarction, Constriction, Pathologic, Foramen Ovale, Patent, Heart Defects, Congenital, Hemorrhage, Ischemic Attack, Transient, Platelet Aggregation Inhibitors, Primary Prevention, Septal Occluder Device, Stroke


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