Patent foramen ovale closure reduces recurrent stroke risk in cryptogenic stroke: A systematic review and meta-analysis of randomized controlled trials

Table 1 Baseline characteristics

Variables	Treatment groups	CLOSE(mean ± SD) or N	CLOSURE I(mean ± SD) or N	PC(mean ± SD) or N	REDUCE(mean ± SD) or N	RESPECT(mean ± SD) or N
Age (yr)	PFO Closure	42.9 ± 10.1	46.3 ± 9.6	44.3 ± 10.2	45.4 ± 9.3	45.7 ± 9.7
	Medical therapy	43.8 ± 10.5	45.7 ± 9.1	44.6 ± 10.1	44.8 ± 9.6	46.2 ± 10
Age range (yr)	PFO Closure	16-60	18-60	< 60	18-59	18-60
	Medical therapy	16-60	18-60	< 60	18-59	18-60
Male	PFO Closure	137	233	92	261	268
	Medical therapy	142	238	114	138	268
Smoker	PFO Closure	68	96	52	63	75
	Medical therapy	69	104	47	25	55
Hypertension	PFO Closure	27	151	49	112	160
	Medical therapy	24	131	58	58	163
Hyper	PFO Closure	30	212	50	-	196
lipidemia	Medical therapy	36	189	62	-	195
Diabetes mellitus	PFO Closure	3	-	5	18	33
	Medical therapy	9	-	6	10	41
CAD	PFO Closure	-	6	4	-	19
	Medical therapy	-	4	4	-	9
Family hx of CAD or stroke	PFO Closure	-	247	53	-	136
	Medical therapy	-	257	40	-	109
CHF	PFO Closure	-	2	-		3
	Medical therapy	-	0	-		0
MI	PFO Closure	0	7	3	-	5
	Medical therapy	0	5	1	-	2
Cardiac catheterization	PFO Closure	-	23	-	-	-
	Medical therapy	-	17	-	-	-
Valvular disease	PFO Closure	-	49	8	-	-
	Medical therapy	-	45	5	-	-
Arrhythmia	PFO Closure	-	26	-	-	-
	Medical therapy	-	19	-	-	-
PTCA	PFO Closure	-	6	-	-	-
	Medical therapy	-	2	-	-	-
PVD	PFO Closure	-	5	3	-	5
	Medical therapy	-	7	2	-	1
Stokes-adams syndrome	PFO Closure	-	4	-	-	-
	Medical therapy	-	3	-	-	-
DVT or PE	PFO Closure	5	0	-	-	-
	Medical therapy	4	4	-	-	-
Migraine	PFO Closure	67	-	47	-	195
	Medical therapy	78	-	38	-	186
Pericarditis	PFO Closure	-	2	-	-	-
	Medical therapy	-	3	-	-	-
Cardio	PFO Closure	-	1	-	-	-
myopathy	Medical therapy	-	0	-	-	-
Index cryptogenic stroke	PFO Closure	238	324	165	441	-
	Medical therapy	235	329	163	223	-
Index TIA	PFO Closure	-	122	33	-	-
	Medical therapy	-	132	42	-	-
TEE with moderate- severe shunt	PFO Closure	-	250	135	348	385
	Medical therapy	-	231	112	173	352
Atrial septal aneurysm > 10 mm	PFO Closure	-	158	47	86	180
	Medical therapy	-	165	45	-	169
> 1 previous TIA or stroke	PFO Closure	10	-	76	68	111
	Medical therapy	7	-	79	24	112

CAD: Coronary artery disease; CHF: Congestive heart failure; DVT: Deep vein thrombosis; MI: Myocardial infarction; PE: Pulmonary embolism; PFO: Patent foramen ovale; TEE: Transesophageal echocardiogram; TIA: Transient ischemic attack.

Table 2 Details of the included randomized controlled trials

Study name	Type of study	Devices used	Follow-up (median or mean), (mo)	PFO closure device	Medical therapy	Primary composite end point
CLOSE	Randomized multicenter	Amplatz PFO Occluder or Cribriform; Starflex; CardioSeal; Intrasept PFO; PFOStar; Helex; Premere; PFO occluder OCCLUTECH; PFO occluder GORE (GSO)	64	238	235	Fatal or nonfatal stroke
CLOSURE I	Prospective, multicenter, randomized, open-label, two-group superiority trial	STARFlex device (NMT Medical)	22	447	462	Composite of stroke or TIA during 2 yr of follow-up, death from any cause during the first 30 d, and death from neurologic causes between 31 d and 2 yr
PC	Multicenter, multinational, randomized, clinical trial	Amplatzer PFO Occluder (St. Jude Medical)	54	204	210	Composite of death, nonfatal stroke, TIA, or peripheral embolism
REDUCE	Multinational, randomized, clinical trial	Gore Helex or Gore Cardioform (WL Gore and Associates) septal occluders	38	441	223	Freedom from recurrent clinical ischemic stroke through at least 24 mo and incidence of new brain infarct
RESPECT	Prospective, multicenter, controlled, randomized, open-label clinical trial	Amplatzer PFO Occluder	71	499	481	Recurrent nonfatal ischemic stroke, fatal ischemic stroke, or early death

CLOSE: Patent Foramen Ovale Closure or Anticoagulants vs Antiplatelet Therapy to Prevent Stroke Recurrence; CLOSURE I: Evaluation of the STARFlex Septal Closure System in Patients with a Stroke and/or Transient Ischemic Attack due to Presumed Paradoxical Embolism through a Patent Foramen Ovale; PC: Percutaneous Closure of Patent Foramen Ovale Using the Amplatzer PFO Occluder with Medical Treatment in Patients with Cryptogenic Embolism; REDUCE: GORE^® HELEX^® Septal Occluder/GORE^® CARDIOFORM Septal Occluder and Antiplatelet Medical Management for Reduction of Recurrent Stroke or Imaging-Confirmed TIA in Patients With Patent Foramen Ovale (PFO); RESPECT: Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment; PFO: Patent foramen ovale; TIA: Transient ischemic attack.