Who benefits from percutaneous closure of patent foramen ovale vs medical therapy for stroke prevention? In-depth and updated meta-analysis of randomized trials

Table 1 Study characteristics

Study name,year	Country of origin	Study design	Indication of PFOC	Total Patients (PFOC + medical therapy), n	Medical therapy	Type of device	Follow-up, in years (mean)
CLOSE[6], 2017	France and Germany	Multicenter, randomized, open-label, superiority trial	Recent stroke due to PFO with atrial septal aneurysm or substantial right-to-left intra-atrial shunt	6631 (238 + 235)	Antiplatelet therapy (aspirin + clopidogrel)1	11 different devices	5.4 PFOC, 5.2 AC-AP
CLOSURE I[11], 2012	United States and Canada	Multicenter, randomized, open-label trial	Stroke or TIA within 6 mo	909 (447 + 462)	Warfarin, aspirin or both	STARFlex device	2
PC Trial[9], 2013	Europe, Canada, Brazil, and Australia	Multicenter, randomized, superiority trial	Stroke, TIA or systemic thromboembolism	414 (204 + 210)	Aspirin+ ticlopidine/clopidogrel	Amplatzer PFO occluder	4.1 PFOC, 4.0 AC/AP
REDUCE[8], 2017	Europe and United States	Multinational, prospective, randomized, controlled, open-label trial	Stroke within 180 d	664 (441 + 223)	Aspirin, aspirin + dipyridamole, or clopidogrel	Helex or Cardioform Septal Occluder	3.2
RESPECT[7], 2017	United States and Canada	Multicenter, randomized, open-label, controlled clinical trial	Stroke within 270 d	980 (499 + 481)	Aspirin + clopidogrel	Amplatzer PFO occluder	5.9
DEFENCE PFO[14], 2018	South Korea	Multicenter, randomized, open-label, superiority	Ischemic stroke in past 6 mos	120 (60 + 60)	Aspirin, aspirin + clopidogrel, aspirin + cilostazol, or warfarin	Amplatzer PFO occluder	2.8

¹There were patients who received anticoagulation alone but the comparator for that arm was antiplatelet therapy not PFOC. AC: Anticoagulation; AP: Anti-platelet; PFOC: Patent foramen ovale closure.

Table 3 Procedural success and complications

Study name, year	Total patients PFOC	Type of Device	Success of device implantation	Success of PFO closure	Procedural complications	Atrial fibrillation/ flutter in PFOC, n (%)	Timing of Afib/flutter	Recurrence of Afib/flutter at f/u
CLOSE[6], 2017	238	11 different devices	234/235 (99.6)	202/228 (88.6)	14/238 (5.9)	11 (4.6)	10/11 within a month	None
CLOSURE I[11], 2012	447	STARFlex device	362/405 (89.4)	315/366 (86.1)	13/402 (3.2)	23 (5.7)	14/23 within a month	6 persistent
PC Trial[9], 2013	204	Amplatzer PFO occluder	188/196 (95.9)	142/148 (95.9)	3/204 (1.5)	6 (2.9)	Timing not defined	1 persistent
REDUCE[8], 2017	441	Helex or Cardioform Septal Occluder	408/413 (98.8)	408/413 (98.8)	11/441 (2.5)	29 (6.6)	24 within 45 d	Not defined
RESPECT[7], 2017	499	Amplatzer PFO occluder	462/464 (99.1)	NR	25/499 (5.0)	7 (1.4)	Periprocedural period	NR
Defense Trial PFO[14], 2018	60	Amplatzer PFO occluder	53/60 (88.3)	53/53 (100)	2/60 (3.3)	2 (3.3)	1 periprocedural	NR

Afib: Atrial fibrillation; f/u: follow-up; NR: Not reported; PFOC: Patent foramen ovale closure.