PASCAL Identifies Who Benefits From Patent Foramen Ovale Closure: JAMA

PFO closure is often considered in young and middle-aged patients with otherwise cryptogenic stroke, although not all identified PFOs are causally linked to stroke. The current analysis directly addresses this uncertainty by assessing whether PASCAL can distinguish patients based on expected benefit versus harm from closure. This study aimed to determine whether the PASCAL classification system can distinguish patients who derive net benefit or net harm from transcatheter PFO closure compared with antithrombotic therapy.

This was a secondary individual participant-level meta-analysis that took place as part of the Systematic, Collaborative, PFO Closure Evaluation (SCOPE) consortium. The meta-analysis was based on data from all 6 randomized controlled trials that compared transcatheter PFO closure plus antithrombotic therapy to antithrombotic therapy alone. These trials were carried out between 2000 and 2017 at various hospitals in North America, Europe, Australia, Brazil, and South Korea. The meta-analysis was carried out between January and August 2025.

Key findings

• A total of 3740 patients were enrolled, with 1889 allocated to PFO closure and 1851 to medical therapy alone.

• The mean (SD) age was 45 (10) years. In total, 2058 patients (55.0%) were male and 1682 (45.0%) were female.

• All patients had a proven PFO and an otherwise cryptogenic ischemic stroke.

• In patients with a PFO-probable diagnosis, PFO closure led to a greater reduction in recurrent ischemic stroke than the increase in late AF over 5 years.

• The absolute reduction in stroke was −2.5% (95% CI, −4.2% to −1.3%), compared with an increase in postperiprocedural AF of 1.3% (95% CI, 0.0% to 2.5%).

• In the PFO-possible group, closure was also beneficial, with a reduction in recurrent strokes of −3.4% (95% CI, −5.4% to −1.3%) and a smaller increase in late AF of 1.1% (95% CI, −0.5% to 2.6%).

• In contrast, in the PFO-unlikely group, PFO closure did not reduce recurrent ischemic stroke (+0.4%; 95% CI, −4.0% to 4.8%) and was associated with a substantially greater increase in late AF of 4.6% (95% CI, 0.3% to 8.9%), indicating net harm.

In young and middle-aged patients with PFO and cryptogenic stroke, the PASCAL system effectively distinguished patients with net benefit and net harm from PFO closure. Patients with PFO-probable or possible had significant stroke reduction with greater benefit than AF risk, whereas patients with PFO-unlikely had increased harm. These findings validate the application of PASCAL patient selection to maximize benefits and prevent unnecessary PFO closure.

Reference:

Saver JL, Kent DM, Kasner SE, et al. Patent Foramen Ovale Closure in Stroke and the PASCAL Classification System. JAMA Neurol. Published online January 26, 2026. doi:10.1001/jamaneurol.2025.5446