Device Closure for High-Risk PFO - DEFENSE-PFO

Contribution To Literature:

The DEFENSE-PFO trial showed that PFO closure among patients with cryptogenic stroke and high-risk PFO was superior to medical management alone in reducing the primary endpoint including recurrent ischemic strokes.

Description:

The goal of the trial was to assess the impact of patent foramen ovale (PFO) closure compared with medical therapy among patients with cryptogenic stroke and with evidence of high-risk PFO.   

Study Design

Patients with high-risk PFO were randomized in a 1:1 fashion to either PFO closure (n = 60) or medical management (n = 60). PFO closure was performed with the Amplatzer PFO Occluder, St. Jude Medical. All patients received either antiplatelet therapy or anticoagulation chosen by the local investigator. Patients who underwent PFO closure were generally recommended to start a dual antiplatelet regimen (aspirin 100 mg/day + clopidogrel 75 mg/day) for at least 6 months after the procedure.

  • Total number screened: 450
  • Total number of enrollees: 120
  • Duration of follow-up: 2 years (median 2.8 years)
  • Mean patient age: 51.8 years
  • Percentage female: 44%

Inclusion criteria:

  • Cryptogenic stroke within 6 months
  • High-risk PFO with right-to-left shunting on transesophageal echocardiography: PFO with atrial septal aneurysm, hypermobility (phasic septal excursion into either atrium ≥10 mm), or PFO size (maximum separation of the septum primum from the secundum) ≥2 mm

Exclusion criteria:

  • History of myocardial infarction or unstable angina
  • History of intracranial bleeding
  • Pre-existing neurological disorders
  • Left ventricular systolic dysfunction with aneurysm or akinesia
  • Contraindications to antiplatelet therapy, or an underlying malignancy

Other salient features/characteristics:

  • Diabetes: 12%, hypertension: 24%
  • mRS 2-3: 23%
  • PFO with no shunt: 42%, presence of atrial septal aneurysm: 11%

At 6 months, DAPT among patients receiving PFO closure vs. medical management, was 57.7% vs. 51.9%, p = 0.69; warfarin 7.7% vs. 23.1%, p = 0.05.

Principal Findings:

The trial was terminated early. The primary outcome, composite of stroke, vascular death, or Thrombolysis in Myocardial Infarction (TIMI)-defined major bleeding, over 2 years, for PFO closure vs. medical management, was 0 vs. 12.9%, p = 0.013.

  • Ischemic stroke: 0 vs. 10.5%, p = 0.023
  • Vascular death: 0 vs. 0
  • TIMI major bleeding: 0 vs. 4.9%, p = 0.15

Secondary outcomes for PFO closure vs. medical management:

  • Hemorrhagic stroke: 0 vs. 2.5%, p = 0.3
  • Transient ischemic attack: 0 vs. 2.0%, p = 0.32
  • Systemic embolism: 0 vs. 0
  • New ischemic lesion on magnetic resonance imaging: 8.8% vs. 18.4%, p = 0.24

Interpretation:

The results of this trial indicate that PFO closure among patients with cryptogenic stroke and high-risk PFO (atrial septal aneurysm, hypermobility, or large size) was superior to medical management alone in reducing the primary endpoint including recurrent ischemic strokes up to 2 years of follow-up.

One caveat is that the trial was terminated early and so was underpowered for the primary endpoint. However, the overall results of this trial are similar to those noted in recent PFO closure trials such as REDUCE and CLOSURE. The RESPECT trial showed a benefit with PFO closure on long-term follow-up (>5 years).

References:

Lee PH, Song JK, Kim JS, et al. Cryptogenic Stroke and High-Risk Patent Foramen Ovale: The DEFENSE-PFO Trial. J Am Coll Cardiol 2018;Mar 12:[Epub ahead of print].

Presented by Dr. Jae-Kwan Song at the American College of Cardiology Annual Scientific Session (ACC 2018), Orlando, FL, March 12, 2018.

Clinical Topics: Anticoagulation Management, Congenital Heart Disease and Pediatric Cardiology, Noninvasive Imaging, Congenital Heart Disease, CHD and Pediatrics and Imaging, Echocardiography/Ultrasound, Magnetic Resonance Imaging

Keywords: ACC18, ACC Annual Scientific Session, Aneurysm, Anticoagulants, Aspirin, Brain Ischemia, Echocardiography, Transesophageal, Embolism, Foramen Ovale, Patent, Heart Defects, Congenital, Ischemic Attack, Transient, Magnetic Resonance Imaging, Myocardial Infarction, Platelet Aggregation Inhibitors, Septal Occluder Device, Stroke, Vascular Diseases, Warfarin


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