More patients needed in clinical trials to find treatment for patent foramen ovale (PFO)

The American Heart Association and the American College of Cardiology are calling on doctors to enroll more patients in clinical trials for catheter-based closure of patent foramen ovale (PFO), a condition caused when an opening between the two chambers of the heart fails to close at birth.

Due to a lack of conclusive research on the management of PFO after stroke or transient ischemic attack, there is currently no clearly established treatment for this condition.

This "call to action" advisory is published in Circulation: Journal of the American Heart Association and the Journal of the American College of Cardiology. The American Academy of Neurology has affirmed the value of this science advisory.

The advisory writing group notes there are a number of ongoing clinical trials looking at patients with PFO and cryptogenic strokes, which are strokes with no identifiable cause after an extensive search. Enrollment in the trials has lagged and the off-label use of PFO closure devices has accelerated, jeopardizing the funding of some studies and the scientific validity of others. "Off-label" indicates when a device or drug is used to treat a condition not listed on its label. This is a common practice, especially for older drugs or devices that perhaps have found new uses but not been put through the rigors of FDA testing and approval for the new use.

"We must have enough patients followed for an adequate time in these trials to make the data valid and the findings strong," said Patrick O'Gara, M.D., chair of the writing group and director of Clinical Cardiology at Brigham and Women's Hospital in Boston. "The completion and peer review of these trials are critical to establishing the evidence base needed to help us make informed decisions regarding the best care for patients with this condition."

Potential treatments for PFO are important for reducing stroke risk. The advisory cites research that shows PFO present in 33.8 percent to 43.9 percent of patients with cryptogenic stroke. A PFO is usually detected by echocardiography during evaluations after a stroke.

Although "optimal" treatment for PFO isn't established, current options for treatment include drug therapy with either anti-platelet agents like aspirin or vitamin K antagonists such as warfarin, surgical repair, or closing the opening with catheter-based (percutaneous) devices. Surgical repair is not usually recommended unless a patient is already undergoing surgery for another reason.

Current American Heart Association/American Stroke Association guidelines recommend anti-platelet medication as the first-line therapy for PFO. Warfarin should be considered if there is an additional indication for anticoagulation. They say that there isn't enough evidence to recommend closing a PFO after a first stroke, but that closure may be considered for patients with recurrent cryptogenic stroke despite optimal medical therapy.

The choice between drug therapy and catheter-based repair has been intensely debated. To date, adequately powered, randomized, prospective clinical trials comparing drug therapy with catheter-based repair have yet to be completed.

Three Food and Drug Administration (FDA) advisory committee meetings (1997, 2002 & 2007) have affirmed the need for completing appropriately sized randomized controlled clinical trials to compare drug therapy with percutaneous device closure. As yet, no device for PFO closure is approved by the FDA.

In addition to the call for doctors to refer more patients to the ongoing trials, the advisory group recommends the data from these trials should be pooled where appropriate and that the "off-label" use of closure devices should be curtailed.

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