Patent foramen ovale closure, antiplatelet therapy or anticoagulation therapy alone for management of cryptogenic stroke? A clinical practice guideline

Options for the secondary prevention of stroke in patients younger than 60 years who have had a cryptogenic ischaemic stroke thought to be secondary to patent foramen ovale (PFO) include PFO closure (with antiplatelet therapy), antiplatelet therapy alone, or anticoagulants. International guidance and practice differ on which option is preferable.

The BMJ Rapid Recommendations panel used a linked systematic review(1) triggered by three large randomised trials published in September 2017 that suggested PFO closure might reduce the risk of ischaemic stroke more than alternatives.(2-4) The panel felt that the studies, when considered in the context of the full body of evidence, might change current clinical practice. 5 The linked systematic review finds that PFO closure prevents recurrent stroke relative to antiplatelet therapy, but possibly not relative to anticoagulants, and is associated with procedural complications and persistent atrial fibrillation. 1 The review also presents evidence regarding the role of anticoagulants or antiplatelet therapy when PFO closure is not acceptable or is contraindicated.

This expert panel make a

Strong recommendation in favour of PFO closure plus antiplatelet therapy compared with antiplatelet therapy alone

Weak recommendation in favour of PFO closure plus antiplatelet therapy compared with anticoagulants

Weak recommendation in favour of anticoagulants compared with antiplatelet therapy.

The largest challenge in making our recommendation was the low quality evidence for the comparisons that included anticoagulants. We summarised all the highest quality available evidence separately for antiplatelet therapy and anticoagulants because the evidence suggests it is likely their effectiveness and adverse effects differ, and clinicians and patients should be aware of these likely differences. Our panel believes that the mechanism of benefit with PFO closure is prevention of venous clots crossing the PFO. Anticoagulants are likely to be substantially more effective in preventing such clots from initially arising than antiplatelet agents.

Box 1 shows the articles and linked evidence in this Rapid Recommendation package. The main infographic presents the recommendations as three paired comparisons, together with an overview of the absolute benefits and harms informing each re-commendation, according to the GRADE methodology.