DEFENSE-PFO Trial: Device Closure vs Medication for Cryptogenic Stroke Patients With High-Risk PFO Anatomy (Lee et al., 2018)
In patients with cryptogenic ischemic stroke and HIGH-RISK PFO anatomy (atrial septal aneurysm, septal hypermobility with phasic excursion ≥10 mm, or PFO size ≥2 mm), does transcatheter PFO closure reduce 2-year stroke / vascular death / TIMI major bleeding compared with medication-only therapy? Confirmed the morphology-enrichment hypothesis operationalized by CLOSE (2017).
Lee PH et al. (JACC 2018;71:2335-2342) · doi:10.1016/j.jacc.2018.02.046 · 120 patients
Population
Included
- Cryptogenic ischemic stroke
- PFO with HIGH-RISK anatomy by TEE: atrial septal aneurysm, septal hypermobility (phasic septal excursion into either atrium ≥10 mm), or PFO size (maximum separation of septum primum from secundum) ≥2 mm
- Adequate workup excluding alternative stroke etiologies
Excluded
- Identifiable competing stroke mechanism
- PFO without any of the three high-risk anatomic features
- Contraindication to PFO closure or to antiplatelet/anticoagulation therapy
Primary Outcome
2-year composite of stroke, vascular death, or TIMI-defined major bleeding
Negligible absolute difference
Primary composite at 2 years (KM)
Safety
Atrial fibrillation (procedure-related)
3.3%
0%
Procedure-related nonfatal atrial fibrillation occurred in 2 of 60 closure patients (3.3%); pericardial effusion in 1 (1.7%); pseudoaneurysm in 1 (1.7%). No comparable procedural complications in the medication-only arm. Source: Lee PH et al., JACC 2018;71:2335-2342.
Trial Design
Type
- Investigator-initiated, multicenter, randomized, open-label superiority trial with blinded endpoint adjudication
- 1:1 randomization (PFO closure : medication-only)
- 2 sites in Korea (Asan Medical Center, Seoul St Mary's Hospital)
- HIGH-RISK PFO anatomy required (atrial septal aneurysm, hypermobility, or size ≥2 mm)
- Small sample size (N=120); confirmed morphology-enrichment hypothesis from the 2017 NEJM cluster
Timeline
Enrolled September 2011 to October 2017; 2-year follow-up; published JACC 2018
N
120
Enrollment
120 Korean patients (60 closure / 60 medication-only) at 2 sites (Asan Medical Center, Seoul St Mary's Hospital). Enrolled September 2011 to October 2017. 2-year follow-up. High-risk PFO anatomy required (atrial septal aneurysm, septal hypermobility ≥10 mm, or PFO size ≥2 mm). Published JACC 2018.
ClinicalTrials.gov
NCT01550588Bedside Pearl
DEFENSE-PFO (JACC 2018): in 120 Korean patients with cryptogenic stroke and HIGH-RISK PFO anatomy (atrial septal aneurysm, hypermobility ≥10 mm, or PFO size ≥2 mm), closure beat medical therapy on the 2-year composite of stroke / vascular death / TIMI major bleeding (0/60 vs 6/60, KM 2-year rate 12.9%, log-rank P=0.013). 2-year ischemic stroke 0% vs 10.5% (P=0.023). Confirms the morphology-enrichment hypothesis from CLOSE and RESPECT long-term subgroup.