An updated practice advisory from the American Academy of Neurology does not recommend the routine use of catheter-based closure of patent foramen ovale in patients with a history of cryptogenic ischemic stroke.
“Because of the limitations of the efficacy evidence and the potential for serious adverse effects, we judge the risk-benefit trade-offs of PFO [patent foramen ovale] closure by either the STARFlex or AMPLATZER PFO Occluder to be uncertain,” wrote Steven Messé, MD, associate professor of neurology at the University of Pennsylvania, Philadelphia, and his associates. “In rare circumstances, such as recurrent strokes despite adequate medical therapy with no other mechanism identified, clinicians may offer the AMPLATZER PFO Occluder if it is available,” they noted.
They also supported antiplatelet agents over anticoagulants unless patients have another indication for blood thinners, noting “the uncertainty surrounding the benefit of anticoagulation in the setting of PFO, and anticoagulation’s well-known harm profile.”
PFO affects about one in four individuals overall and up to half of cryptogenic stroke patients. The previous (2004) version of this practice advisory cited insufficient evidence to guide optimal therapy for secondary stroke prevention in these patients ( Neurology. 2004;Apr 13;62:1042-50 ). To update the guideline, Dr. Messé and his associates searched the literature for relevant randomized studies, excluding transient ischemic attacks when feasible because of their subjective nature, and focusing on intention-to-treat analyses to reduce bias ( Neurology. 2016 Jul 27;doi: 10.1212/WNL.0000000000002961 ).
Among 809 initial articles, 5 were considered relevant – a randomized, open-label, multicenter study of the STARFlex device (CLOSURE I), two randomized, controlled trials of the AMPLATZER PFO Occluder (PC Trial and RESPECT), and two randomized studies of warfarin versus aspirin in cryptogenic stroke patients, the experts said.
Percutaneous PFO closure with the STARFlex device did not appear to prevent secondary stroke, compared with medical therapy alone, based on a small positive estimated difference in risk of about 0.1%, and a 95% confidence interval that crossed zero (–2.2% to 2.0%). In contrast, the AMPLATZER PFO Occluder decreased the risk of secondary stroke by about 1.7% (95% CI, –3.2% to –0.2%), but upped the risk of procedural complications by more than 3%, and also slightly increased the risk of new-onset atrial fibrillation (1.6%; 95% CI, 0.1% to 3.2%).
Efficacy data were insufficient to clearly support anticoagulants over antiplatelet therapy for recurrent stroke prevention, the experts concluded. Compared with antiplatelet therapy, anticoagulation was associated with a 2% increase in risk of recurrent stroke, but the 95% confidence interval for this estimate was wide and crossed zero. “In the absence of another indication for anticoagulation, clinicians may routinely offer antiplatelet medications instead of anticoagulation to patients with cryptogenic stroke and PFO,” they wrote. “In rare circumstances, such as stroke that recurs while a patient is undergoing antiplatelet therapy, clinicians may offer anticoagulation to patients with cryptogenic stroke and PFO.”
Their strongest recommendation was to counsel patients who are considering percutaneous PFO closure “that having a PFO is common; it occurs in about 1 in 4 people; it is impossible to determine with certainty whether their PFOs caused their strokes or TIAs; the effectiveness of the procedure for reducing stroke risk remains uncertain; and the procedure is associated with relatively uncommon, yet potentially serious, complications.”
The practice advisory was supported by the American Academy of Neurology. Dr. Messé disclosed ties to GlaxoSmithKline and WL Gore & Associates and has been an investigator for the REDUCE and CLOSURE-I trials. Five of his coauthors have been investigators for RESPECT, CLOSURE-I, and REDUCE, have been editors for Neurology, and have received compensation from Genentech, Pfizer, Gilead Sciences, and other pharmaceutical companies. One coauthor had no disclosures.