title: Anticoagulant vs. antiplatelet therapy in patients with cryptogenic stroke and patent foramen ovale: an individual participant data meta-analysis.
abstract: OBJECTIVE
  The preferred antithrombotic strategy for secondary prevention in patients with cryptogenic stroke (CS) and patent foramen ovale (PFO) is unknown. We pooled multiple observational studies and used propensity score-based methods to estimate the comparative effectiveness of oral anticoagulation (OAC) compared with antiplatelet therapy (APT).
  
  
  RESULTS
  Individual participant data from 12 databases of medically treated patients with CS and PFO were analysed with Cox regression models, to estimate database-specific hazard ratios (HRs) comparing OAC with APT, for both the primary composite outcome [recurrent stroke, transient ischaemic attack (TIA), or death] and stroke alone. Propensity scores were applied via inverse probability of treatment weighting to control for confounding. We synthesized database-specific HRs using random-effects meta-analysis models. This analysis included 2385 (OAC = 804 and APT = 1581) patients with 227 composite endpoints (stroke/TIA/death). The difference between OAC and APT was not statistically significant for the primary composite outcome [adjusted HR = 0.76, 95% confidence interval (CI) 0.52-1.12] or for the secondary outcome of stroke alone (adjusted HR = 0.75, 95% CI 0.44-1.27). Results were consistent in analyses applying alternative weighting schemes, with the exception that OAC had a statistically significant beneficial effect on the composite outcome in analyses standardized to the patient population who actually received APT (adjusted HR = 0.64, 95% CI 0.42-0.99). Subgroup analyses did not detect statistically significant heterogeneity of treatment effects across clinically important patient groups.
  
  
  CONCLUSIONS
  We did not find a statistically significant difference comparing OAC with APT; our results justify randomized trials comparing different antithrombotic approaches in these patients.
authors.affiliation: Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center/Tufts University School of Medicine, 800 Washington St, Box 63, Boston, MA 02111, USA Department of Neurology, Tufts Medical Center/Tufts University School of Medicine, Boston, MA, USA dkent1@tuftsmedicalcenter.org.
authors.forename: David M
authors.initials: DM
authors.lastname: Kent
authors.affiliation: Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center/Tufts University School of Medicine, 800 Washington St, Box 63, Boston, MA 02111, USA Center for Evidence-Based Medicine, School of Public Health, Brown University, Providence, RI, USA Department of Health Services, Policy, and Practice, School of Public Health, Brown University, Providence, RI, USA.
authors.forename: Issa J
authors.initials: IJ
authors.lastname: Dahabreh
authors.affiliation: Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center/Tufts University School of Medicine, 800 Washington St, Box 63, Boston, MA 02111, USA.
authors.forename: Robin
authors.initials: R
authors.lastname: Ruthazer
authors.affiliation: Department of Neurology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Furlan
authors.affiliation: Department of Neurology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Weimar
authors.affiliation: Neurology Department, Hospital Universitari Doctor Josep Trueta Institut D'Investigació Biomèdica de Girona, Girona, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Serena
authors.affiliation: Department of Cardiology, Swiss Cardiovascular Center, Inselspital, University of Bern, Bern, Switzerland.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Meier
authors.affiliation: Inselspital, University of Bern, Bern, Switzerland.
authors.forename: Heinrich P
authors.initials: HP
authors.lastname: Mattle
authors.affiliation: Department of Public Health and Primary Care, Cambridge University, Cambridge, UK.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Di Angelantonio
authors.affiliation: Stroke Unit and Division of Cardiovascular Medicine, University of Perugia, Perugia, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Paciaroni
authors.affiliation: Department of Medicine, LKH-Graz West, Graz, Austria.
authors.forename: Herwig
authors.initials: H
authors.lastname: Schuchlenz
authors.affiliation: Division of Cardiology, Columbia University, New York, NY, USA.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Homma
authors.affiliation: Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center/Tufts University School of Medicine, 800 Washington St, Box 63, Boston, MA 02111, USA.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Lutz
authors.affiliation: Department of Neurology, Tufts Medical Center/Tufts University School of Medicine, Boston, MA, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Thaler
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D005260:Female; D054092:Foramen Ovale, Patent / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D064887:Observational Studies as Topic; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D057216:Propensity Score; D020521:Stroke / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors
keywords: Cardiogenic stroke; Cryptogenic stroke; Medical stroke treatment; Patent foramen ovale; Secondary stroke prevention