title: Percutaneous closure versus medical therapy alone for cryptogenic stroke patients with a patent foramen ovale: meta-analysis of randomized controlled trials.
abstract: Of cryptogenic stroke patients younger than 55 years of age, up to 61% have had a patent foramen ovale (PFO). Observational studies have revealed reductions in recurrent neurologic events through PFO closure versus medical therapy, and randomized controlled trials have shown nonsignificant trends toward benefit. We systematically searched for randomized controlled trials of percutaneous PFO closure with medical therapy versus medical therapy alone in patients with cryptogenic stroke and performed a meta-analysis of treatment outcomes. The primary endpoint was combined death, stroke, and transient ischemic attack. We included 3 trials. Of 2,303 total patients, 1,150 underwent PFO closure and 1,153 received medical therapy (median follow-up period, 2.6 yr). The pooled incidence of the primary endpoint was 1.2 events per 100 patient-years in the closure group (95% confidence interval [CI], 0.2-2.3) and 1.8 in the therapy group (95% CI, 0.7-2.9) (P=0.32); the number needed to treat was 167 (range, 100-500). The corresponding pooled hazard ratio was 0.67 (95% CI, 0.44-1.01; P=0.054) in favor of closure. Closure was associated with an increased risk of atrial fibrillation: relative risk=3.51 (95% CI, 1.44-8.55; P=0.006). When stratified by device, use of the Amplatzer™ PFO Occluder resulted in significant stroke-prevention benefit over medical therapy alone: hazard ratio=0.44 (95% CI, 0.21-0.95; P=0.037). When compared with medical therapy alone, PFO closure with medical therapy showed a trend toward a decreased hazard of combined events, although the absolute event reduction was small and the number needed to treat was high.
authors.affiliation: Cardiology Service (Drs. Ferguson, Pickett, and Villines) and Interventional Cardiology (Dr. Ferguson), Walter Reed National Military Medical Center, Bethesda, Maryland 20889; and Cardiovascular Division, Department of Medicine (Dr. Hulten), Brigham and Women's Hospital, Boston, Massachusetts 02115.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Pickett
authors.affiliation: Cardiology Service (Drs. Ferguson, Pickett, and Villines) and Interventional Cardiology (Dr. Ferguson), Walter Reed National Military Medical Center, Bethesda, Maryland 20889; and Cardiovascular Division, Department of Medicine (Dr. Hulten), Brigham and Women's Hospital, Boston, Massachusetts 02115.
authors.forename: Todd C
authors.initials: TC
authors.lastname: Villines
authors.affiliation: Cardiology Service (Drs. Ferguson, Pickett, and Villines) and Interventional Cardiology (Dr. Ferguson), Walter Reed National Military Medical Center, Bethesda, Maryland 20889; and Cardiovascular Division, Department of Medicine (Dr. Hulten), Brigham and Women's Hospital, Boston, Massachusetts 02115.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Ferguson
authors.affiliation: Cardiology Service (Drs. Ferguson, Pickett, and Villines) and Interventional Cardiology (Dr. Ferguson), Walter Reed National Military Medical Center, Bethesda, Maryland 20889; and Cardiovascular Division, Department of Medicine (Dr. Hulten), Brigham and Women's Hospital, Boston, Massachusetts 02115.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Hulten
mesh_terms: D000293:Adolescent; D000328:Adult; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D006328:Cardiac Catheterization / Q000009:adverse effects / Q000295:instrumentation / Q000401:mortality; D003131:Combined Modality Therapy; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D054092:Foramen Ovale, Patent / Q000150:complications / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D006801:Humans; D002546:Ischemic Attack, Transient / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011474:Prosthesis Design; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012307:Risk Factors; D055989:Septal Occluder Device; D020521:Stroke / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors
keywords: Cerebral infarction/etiology; foramen ovale, patent/complications/drug therapy/economics/surgery; ischemic attack, transient/etiology/prevention & control; logistic models; meta-analysis; odds ratio; randomized controlled trials as topic; risk factors; septal occluder device; stroke/drug therapy/etiology/prevention & control