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. 2020 Nov 24;15:e15. doi: 10.15420/icr.2019.27

Table 2: Randomised Trials Comparing Patent Foramen Ovale Closure with Medical Therapy.

Study Year Device n Endpoints Results Comments
CLOSURE 1[12] 2012 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)
Left atrial thrombus formation in closure group
Inadequate closure at 2 years
PC Trial[13] 2013 Amplatzer PFO Occluder 414 Composite of death, stroke, TIA or peripheral embolism at 4,5 years Non-significant reduction in primary endpoint
(HR 0.63; 95% CI [0.24–1.62]; p=0.34)
Underpowered trial
High volume of crossover to PFO closure during follow-up
RESPECT[18,19] 2013
Long-term data published in 2017
Amplatzer PFO Occluder 980 Composite of early death, stroke or TIA Non-significant reduction in primary endpoint at median follow-up 2.1 years
(HR 0.49; 95% CI [0.22–1.11]; p=0.08)
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)
As treated analysis shows a benefit in favour of closure even at the early timepoint.
CLOSE[22] 2017 11 approved devices (Amplatzer PFO Occluder >50%) 663 Fatal or non-fatal stroke Significant reduction in stroke with occlusion compared with antiplatelet therapy only
(HR 0.03, 95% CI [ 0-0.26]; p<0.001)
1:1:1 randomisation PFO closure versus antiplatelets versus anti-coagulation
Gore REDUCE[20] 2017 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 3.2 years
(HR 0.23; 95% CI [0.09–0.62]; p=0.002)
Significant reduction in new brain infarction
(RR 0.51; 95% CI [0.29–0.91]; p=0.04)
2:1 randomisation to PFO closure
DEFENSE PFO[21] 2018 Amplatzer PFO Occluder 120 Stroke, vascular death or Major bleeding at 2-year follow-up Significant reduction in primary endpoint with PFO closure. No events in PFO closure arm versus 12.9% 2-year event rate in medication only arm (p=0.013)

PFO = patent foramen ovale; TIA = transient ischaemic attack.