PFO Closure for Stroke: A Call to Revise the Guidelines
An updated guideline issued this year by the American Heart Association and American Stroke Association (AHA/ASA) regarding the closure of patent foramen ovale (PFO) for cryptogenic stroke revised an earlier document to indicate that current data do not support a benefit in this patient population.
At TCT 2014, neurologist David E. Thaler, MD, PhD, of Tufts University School of Medicine, Boston, Mass., argued that the new recommendation — class III, level of evidence A — should be upgraded.
The 2014 update in the journal Stroke states: “For patients with a cryptogenic ischemic stroke or transient ischemic attack and a PFO without evidence for deep vein thrombosis, available data do not support a benefit for PFO closure (class III, level of evidence A).” The recommendation from the original guideline published in 2011 stated: “There are insufficient data to make a recommendation regarding PFO closure in patients with stroke and PFO (class IIb, level of evidence C).”
“I submit that the recommendation of class III evidence needs to be changed,” Thaler said. “The [AHA/ASA] committee erred in interpreting negative trials. I think they should have supported at least a class IIb recommendation, maybe even class IIa, but certainly not class III.”
Changes to classification
During his presentation, Thaler discussed the overall classification of guideline recommendations and the changes to the level of evidence from 2011 to 2014. Previously, class III evidence indicated that risk was equal to or greater than the benefit of a procedure or treatment, which therefore should not be performed or administered since it is not helpful and may be harmful. Now, a new division within class III can indicate that a procedure or treatment is either harmful or there is no proven benefit. “The [AHA/ASA] writing committee chose this ‘box’ to put the PFO closure story into — no proven benefit,” Thaler said.
He noted that there is a common fallacy that a superiority trial that is not positive is the same as neutrality or equivalence of treatment. “Failing to prove that two populations are different is not the same as proving that two populations are the same,” he said.
A class IIb categorization of PFO closure for cryptogenic stroke would indicate that benefit outweighs risk, according to Thaler. “Nobody has made the argument that [PFO closure] is a particularly risky intervention. The trials did not have a strong suggestion that there was risk,” he said.
In the guideline, the committee wrote, “Although the point estimates favored device closure to various degrees in each trial, none of the studies demonstrated a statistically significant finding for their primary endpoint in an intention-to-treat analysis.”
Thaler said the committee incorrectly declared neutrality despite the fact that the confidence interval does not rule out potential benefit and point estimates are favorable.
Recently, Thaler, along with Jeffrey L. Saver, MD, John D. Carroll, MD, and Richard W. Smalling, MD, PhD, submitted a letter to Stroke asking for a correction of the class III recommendation, stating that “it is an extreme violation of the norms of evidence-based medicine to conclude that there is definitely no benefit of an intervention when the best estimate of treatment effect available from randomized controlled trials actually suggests benefit.”
During a panel discussion about this issue, Sanjay Kaul, MD, from Cedars-Sinai Medical Center, Los Angeles, Calif., said he does not discriminate between class IIIa or class IIb recommendations. “I leave it up to the patient’s judgment and preference. I tell them that the evidence is not very strong; it is weak at best. This is an option that is available … off label. But I still do not tell them that this is evidence based,” he concluded.
- Thaler reports receiving grant/research support from the National Institute of Neurological Disorders and Stroke as well as consultant fees/honoraria from Coherex and St. Jude Medical.
- Kaul reports receiving consultant fees/honoraria/serving on the speaker's bureau for AstraZeneca, the FDA, Merck/Schering Plough and The Medicines Company and having equity in Cordis.