Device Closure of Patent Foramen Ovale After Stroke: Pooled Analysis of Completed Randomized Trials

Abstract

Background: The comparative effectiveness of percutaneous closure of patent foramen ovale (PFO) plus medical therapy versus medical therapy alone for cryptogenic stroke is uncertain.

Objectives: The authors performed the first pooled analysis of individual participant data from completed randomized trials comparing PFO closure versus medical therapy in patients with cryptogenic stroke.

Methods: The analysis included data on 2 devices (STARFlex [umbrella occluder] [NMT Medical, Inc., Boston, Massachusetts] and Amplatzer PFO Occluder [disc occluder] [AGA Medical/St. Jude Medical, St. Paul, Minnesota]) evaluated in 3 trials. The primary composite outcome was stroke, transient ischemic attack, or death; the secondary outcome was stroke. We used log-rank tests and unadjusted and covariate-adjusted Cox regression models to compare device closure versus medical therapy.

Results: Among 2,303 patients, closure was not significantly associated with the primary composite outcome. The difference became significant after covariate adjustment (hazard ratio [HR]: 0.68; p = 0.049). For the outcome of stroke, all comparisons were statistically significant, with unadjusted and adjusted HRs of 0.58 (p = 0.043) and 0.58 (p = 0.044), respectively. In analyses limited to the 2 disc occluder device trials, the effect of closure was not significant for the composite outcome, but was for the stroke outcome (unadjusted HR: 0.39; p = 0.013). Subgroup analyses did not identify significant heterogeneity of treatment effects. Atrial fibrillation was more common among closure patients.

Conclusions: Among patients with PFO and cryptogenic stroke, closure reduced recurrent stroke and had a statistically significant effect on the composite of stroke, transient ischemic attack, and death in adjusted but not unadjusted analyses.

Keywords: cryptogenic stroke; meta-analysis; transient ischemic attack.

Figure 1. Subgroup Analysis: Device versus Medical Therapy

Per unadjusted hazard ratios (HR) for study-stratified Cox proportional hazard, pre-specified subgroup analyses did not show any statistically significant heterogeneity of treatment effect for the primary composite outcome. CI = confidence interval; Ev = event; PT = patient; TEE = transesophageal echocardiography.

Central Illustration. Patent Foramen Ovale Closure in Stroke Trials: Kaplan-Meier curves comparing device closure versus medical therapy

Kaplan-Meier curves comparing device closure (red) versus medical therapy (blue). Results shown for all trials pooled and for Amplatzer device trials only, and for both the primary composite and ischemic stroke outcomes. Secondary composite outcome (including only early death) was statistically significant for both the 3 trial (log rank p-value = 0.0488) and the Amplatzer only analysis (log rank p-value= p = 0.0451).