Anticoagulant vs. antiplatelet therapy in patients with cryptogenic stroke and patent foramen ovale: an individual participant data meta-analysis

Eur Heart J. 2015 Sep 14;36(35):2381-9. doi: 10.1093/eurheartj/ehv252. Epub 2015 Jul 3.


Aims: 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).

Methods and 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.

Conclusion: We did not find a statistically significant difference comparing OAC with APT; our results justify randomized trials comparing different antithrombotic approaches in these patients.

Keywords: Cardiogenic stroke; Cryptogenic stroke; Medical stroke treatment; Patent foramen ovale; Secondary stroke prevention.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Review

MeSH terms

  • Anticoagulants / therapeutic use*
  • Female
  • Foramen Ovale, Patent / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Observational Studies as Topic
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Propensity Score
  • Stroke / prevention & control*


  • Anticoagulants
  • Platelet Aggregation Inhibitors