In patients younger than 60 years, patent foramen ovale (PFO) closure plus antiplatelet therapy is a better strategy for preventing recurrent ischemic stroke than indefinite anticoagulant therapy without closure, according to a recommendation from an expert panel after a systematic literature review.
When compared with the alternative strategy of indefinite anticoagulant therapy for those patients “open to all options,” the recommendation was labeled only “weak” on the basis of the GRADE classification system used by the panel to rate treatment strategies. However, the recommendation for PFO closure plus antiplatelets becomes “strong” if anticoagulation therapy is contraindicated or declined as a treatment option.
The new recommendations were largely driven by three multicenter studies of that were published simultaneously last year. (N Engl J Med. 2017 Sep 14;377:1011-21; 1022-32; 1033-42). However, these and previous studies did not provide adequate data on risks and benefits for all options, which the authors emphasized in guidelines meant to help clinicians weigh options.
Weak means that clinicians “should recognize that different choices will be appropriate for different patients,” explained Frederick A. Spencer, MD, professor, division of cardiology, McMaster University, Hamilton, Ontario. Quoting from GRADE definitions, Dr. Spencer, who was the guideline panel chair, explained that weak recommendations are the product of uncertainties that may affect choice in specific individuals.
In addition to the recommendation for PFO closure plus antiplatelets as either a weak or strong recommendation in relation to the availability of anticoagulation therapy, the guidelines offered one other recommendation. For patients contraindicated or unwilling to undergo PFO closure, anticoagulation therapy was preferred over antiplatelet therapy. This was also labeled a “weak” recommendation.
These guidelines were the product of collaboration between the BMJ and the nonprofit MAGIC (Making GRADE the Irresistible Choice) project. In addition to providing a methodology and structure to organize guideline deliberations among the participating international experts, MAGIC facilitated communication and collaboration through Web-based technology.
This approach was particularly useful for the detailed analyses and debate about relative risks and benefits of treatment alternatives in which direct comparative data were limited. For example, the authors noted that the only randomized comparison of PFO closure to anticoagulation involved just 353 patients. Indirect evidence was therefore added to improve the precision of the estimated benefits and risks. The panel selected PFO closure plus antiplatelet therapy over anticoagulation therapy, because “the most serious complications of PFO closure are usually short term, whereas anticoagulation imposes a long-term burden and increased risk of major bleeding.”
The estimated rate of adverse events associated with PFO is 3.6%, according to data cited in the expert guidelines. Atrial fibrillation accounts for about half of these events. At 5 years, the absolute reduction in stroke from PFO closure versus no intervention is an estimated 8.7%. The panel assumed that most patients would place greater weight on stroke prevention than the largely reversible adverse events associated with PFO closure.
The newly published guidelines include a detailed review of the available data to allow clinicians to counsel patients appropriately. Dr. Spencer cautioned that no recommendation, strong or weak, should be uniformly applied without considering individual patient factors and preferences.
According to Christopher J. White, MD, system chairman for cardiology, Ochsner Medical Center, New Orleans, the guideline committee had no choice but to label PFO closure plus antiplatelet therapy as a “weak” recommendation within the requirements of GRADE. However, Dr. White believes that it should be considered the best option in most patients despite this terminology.
“What I tell patients is that this is a one-and-done procedure,” Dr. White explained. “Without closure, patients must remain on anticoagulation therapy, which involves refilling prescriptions, remaining compliant with daily therapy for life, and accepting an increased risk of bleeding. Once the PFO is closed and endothelialized, no additional anticoagulation treatment is needed.”
There are adverse events associated with PFO closure, but Dr. White called these uncommon and more acceptable than the risks of indefinite anticoagulation therapy, particularly if patients are not fully compliant.
“When I explain the options to patients, most will opt for PFO closure,” Dr. White said.
He also emphasized that the advantage of PFO closure accrues over time.
“When these patients have a stroke at a relatively young age, they may need to be on anticoagulation for decades. Once the PFO is closed, you are saving the patient the burden of lifelong compliance to anticoagulation therapy as well as the costs,” he added. Although the guidelines compared relative benefits of a given strategy over 5 years, the advantage of PFO closure over anticoagulation will keep increasing beyond this point.
Source: Kuipers et al. BMJ 2018 Jul 25;362:K2515