Table 2: Randomised Controlled Trials Comparing Patent Foramen Ovale Closure to Medical Therapy.
| Study | Device | n | Endpoints | Results | Comments |
|---|---|---|---|---|---|
| CLOSURE I[9] | STARFlex Septal Closure System | 909 | Composite of death (0–30 days), neurological death (≥31 days), stroke or TIA at 2-year follow-up | Non-significant reduction in primary endpoint (HR 0.78; 95% CI [0.45–1.35]; p=0.37) | Poor effective closure at 2 years, with evidence of left atrial thrombus formation in closure group |
| PC-Trial[10] | AMPLATZER PFO Occluder | 414 | Composite of death, stroke, TIA or peripheral embolism at mean 4.5 years | Non-significant reduction in primary endpoint (HR 0.63; 95% CI [0.24–1.62]; p=0.34) | Underpowered trial with substantial cross-over during follow-up |
| RESPECT[13,14] | AMPLATZER PFO Occluder | 980 | Composite of early death, stroke or TIA | Non-significant reduction in primary endpoint at median follow-up of 2.1 years (HR 0.49; 95% CI [0.22–1.11]; p=0.08). Subsequent long-term follow up (median 5.9 years) showed significant reduction with closure (HR 0.55; 95% CI [0.31–0.99]; p=0.046) |
Benefit for closure in early as-treated analysis |
| GORE REDUCE[15] | Helex Septal Occluder or Cardioform Septal Occluder | 664 | Co-primary endpoints of clinical stroke and incidence of new brain infarction | Significant reduction in clinical stroke at median follow-up of 3.2 years (HR 0.23; 95% CI [0.09–0.62]; p=0.002). Significant reduction in new brain infarction (relative risk 0.51; 95% CI [0.29–0.91]; p=0.04) |
2:1 randomisation to PFO closure |
| CLOSE[16] | Multiple devices | 663 | Stroke | Significant reduction in stroke with occlusion compared to antiplatelet therapy only (HR 0.03; 95% CI [0.00–0.26]; p<0.001) | 1:1:1 randomisation PFO closure versus antiplatelets versus anticoagulation |
| DEFENSE PFO[17] | AMPLATZER PFO Occluder | 120 | Stroke, vascular death or Thrombolysis In Myocardial Infarction-defined major bleeding at 2-year follow-up | Significant reduction in primary endpoint with PFO closure. No events in PFO closure arm versus a 12.9% 2-year event rate in medication-only arm (p=0.013) |
PFO = patent foramen ovale; TIA = transient ischaemic attack.