"PFO Closure vs. Medical Therapy in Stroke Prevention". The New England Journal of Medicine. 2013.

Clinical Question

Does patent foramen ovale (PFO) closure reduce the risk of recurrent ischemic stroke compared to medical therapy alone in patients 18 to 60 years of age with a history of cryptogenic stroke?

Bottom Line

In patients who had a cryptogenic ischemic stroke and a PFO, closure with the Amplatzer PFO Occluder device did not show a significant benefit over medical therapy alone in the primary intention-to-treat analysis. However, PFO closure was found to be superior to medical therapy alone in the prespecified per-protocol and as-treated analyses, with a low rate of associated risks.

Major Points

Guidelines

Current guidelines do not provide specific recommendations for PFO closure in patients with a cryptogenic stroke due to the mixed evidence from trials.

Design

Prospective, multicenter, randomized, event-driven trial comparing PFO closure to medical therapy alone.
N=980 patients enrolled at 69 sites.
Patients were 18 to 60 years of age with a history of cryptogenic ischemic stroke.
Randomization to PFO closure with the Amplatzer PFO Occluder or medical therapy only.

Population

Inclusion Criteria:
- 18 to 60 years of age
- Cryptogenic ischemic stroke
- PFO identified via transesophageal echocardiography

Exclusion Criteria:
- Identifiable causes of stroke apart from paradoxical embolism
- Significant shunt or atrial septal defect
- Hypercoagulable states

Baseline Characteristics:
- Mean age: 45.9 years
- 51.4% female
- Median follow-up: 2.1 years

Interventions

- PFO closure within 21 days after randomization
- Medical therapy allowed: aspirin, warfarin, clopidogrel, or combined aspirin with extended-release dipyridamole

Outcomes

Primary Outcomes:
- Recurrent nonfatal ischemic stroke, fatal ischemic stroke, or early death after randomization

Secondary Outcomes:
- Complete closure of PFO on the 6-month follow-up transesophageal echocardiogram
- Absence of recurrent symptomatic nonfatal ischemic stroke or cardiovascular death
- Absence of a transient ischemic attack

Criticisms

- Higher dropout rate in the medical-therapy group leading to unequal duration of exposure to the risk of recurrence
- The primary analysis not showing superiority of PFO closure
- Long-term protective benefit of closure remains uncertain due to modest absolute event reduction

Funding

The study was funded by St. Jude Medical.

Further Reading