番茄社区

Closure of the patent foramen ovale (PFO) followed by antiplatelet therapy should be offered to appropriate cryptogenic stroke patients younger than age 60 to reduce stroke recurrence risk, a panel recommended, against current guidelines.

The international multidisciplinary group of experts and patients convened by for its Rapid Recommendations series reviewed and meta-analyzed all relevant available randomized trials, including the three large clinical trials published in 2017 supporting reduced risk of recurrent stroke with PFO closure. Their conclusions were:

• Strong recommendation for closure plus antiplatelet therapy versus antiplatelet therapy alone
• Weak recommendation for closure plus antiplatelet therapy versus anticoagulants
• Weak recommendation for anticoagulants versus antiplatelet therapy, when closure is contraindicated, unacceptable, or unavailable

Generally, guidelines of the and the recommend against routine closure of PFO in patients with cryptogenic stroke – with rare exceptions for patients with deep vein thrombosis or recurrent cryptogenic strokes despite adequate medical therapy. Instead, they recommend antiplatelet (or anticoagulation therapy if indicated for another reason).

"Our guideline differs from the others," co-author Frederick Spencer, MD, of McMaster University in Hamilton, Ontario, told 番茄社区 in an email, in that it:

• "Is more recent so was able to incorporate recent studies
• "Uses the GRADE approach to carefully and transparently evaluate the available data with attempted consideration of what patients would think are more versus less important outcomes
• "Offers recommendations regarding PFO versus antiplatelet and PFO versus anticoagulant therapy, as opposed to generalizing the two forms of medical therapy"

The paper included an explanatory decision-aid style infographic that outlines the recommendations and provides an overview (GRADE summary of findings) of the absolute benefits in terms of reduction in recurrent ischemic stroke.

The absolute reduction of stroke with PFO closure was 8.7% at 5 years compared with antiplatelet therapy alone. The intervention was also associated with a 3.6% absolute risk of adverse events including atrial fibrillation (1.8%), although effects of these are usually short-term, the team wrote in BMJ.

Compared with anticoagulation alone, PFO closure plus antiplatelet therapy may be associated with a small 1.6% absolute reduction in risk of stroke at 5 years, and a 2.0% decrease in absolute bleeding risk, but a 3.6% device- or procedure-related adverse events risk.

The recommendation for anticoagulants over antiplatelets had weak evidence of stroke reduction, wrote the group, which amounted to a 7.1% absolute reduced risk of stroke, a 1.2% increase in major bleeding over 5 years, and little if any effect on risks of death, pulmonary embolism, transient ischaemic attack, or systemic embolism.

"The risk of major bleeding probably increased with anticoagulation," Spencer's group noted.

"Although direct anticoagulants have not been evaluated in PFO, their advantages in terms of convenience may render them, rather than warfarin, the best option for those who choose anticoagulants," they added.

The panel acknowledged the higher relative costs of PFO closure, which carried less weight in these patient-focused recommendations, but added that in the long term, the procedure "may reduce costs as a result of reduced stroke rates and reduction in associated costs."

The researchers noted the limitations include the inability "to stratify our analyses and recommendations by type or generation of PFO closure device because of the limitations in published data and small subset sample sizes."

Further research is needed to determine the relative merit of PFO closure versus anticoagulation alone, versus antithrombotic agents alone in those with small PFOs, as well to identify patient groups most likely to benefit from PFO closure versus medical therapy.

Comment