Catheter delivered devices may be just as effective as drug therapy in treating strokes of unidentified origin

A percutaneous catheter procedure to correct a heart abnormality caused by an open patent foramen ovale (PFO), a flap that should be closed in an adult heart, may be just as effective as drug therapy in treating patients who have had strokes of unidentified origin, perhaps caused by this condition. This first direct comparison of treatments appears in the Aug. 18, 2004 issue of the Journal of the American College of Cardiology.

“These are encouraging data indicating that percutaneous PFO closure appears to be at least as effective as medical treatment,” said Stephan Windecker, M.D., at University Hospital in Bern, Switzerland. “But the best way to find a definitive answer about the best treatment option in this patient population is to refer patients to a trial in which you prospectively randomize between medical treatment and percutaneous PFO closure. Only this type of trial can give you a definitive answer as to what the best treatment is,” Dr. Windecker concluded.

Patent foramen ovale (PFO) is a flap valve that allows blood to flow directly from the right atrium to the left atrium of the fetal heart, when oxygen is supplied from the mother and the developing lungs are not yet in use. After birth, when a newborn begins breathing and blood flows through the lungs, blood pressure increases on the left side of the heart, which generally holds the PFO flap closed.

Although the flap is usually permanently shut by the first birthday, some people still have an open PFO into adulthood. The abnormality usually does not cause any symptoms, but it may play a role in some strokes.

“If you haven’t found any other cause, that is, carotid artery disease, atrial fibrillation or any source of embolism on the left side of the heart, and you find this opening, the patent foramen ovale, then you have a presumptive diagnosis of what we call paradoxical embolism. The paradoxical part is that the embolism travels from the right side of the heart to the left side through this opening,” Dr. Windecker said.

“It’s important to realize that this is a presumptive diagnosis, not a definitive diagnosis. What is thought to be happening is that there are thrombi (blood clots) forming either in the deep veins of the legs or in the heart itself, which can then travel through this opening from the right side of the heart to the left side. Then they can travel through the left atrium and the left ventricle into the brain. If they obstruct an artery there, they cause a stroke,” he added.

The researchers studied the risk of recurrence in 308 patients with cryptogenic stroke, which is a stroke without a clearly identified cause, who also had a PFO. The patients were treated either medically (158 patients) or underwent percutaneous PFO closure (158 patients) between 1994 and 2000. The study was not randomized; patients and physicians decided which treatment they preferred.

After four years, the patients who had undergone percutaneous PFO closure had a lower combined risk of death, another stroke or a transient ischemic attack; however, the difference was not statistically significant. The researchers did observe a significantly lower risk of stroke or TIA among patients who achieved complete PFO closure with the percutaneous procedure (no leakage seen with an ultrasound examination) and those patients who had multiple events prior to entering the study.

Dr. Windecker said it is too early to recommend changes in typical treatment based on this study alone. He recommended that patients with PFO and cryptogenic stroke be referred to ongoing trials that randomly assign them to either a catheter procedure or medical treatment.

“Percutaneous PFO closure is a promising technique in patients with PFO and cryptogenic stroke and it warrants further evaluation in randomized clinical trials,” Dr. Windecker said.

Joseph L. Blackshear, M.D., F.A.C.C., at the Mayo Clinic in Jacksonville, Fla., who wrote an editorial in the journal, urged that the link between stroke and PFO be carefully studied in individual patients before enrolling them in such trials.

“The link between PFO and stroke is tenuous; there is scant evidence to suggest that it should be considered the default diagnosis in all patients. Unless this link can be better established, conducting clinical trials will often involve treating patients for one condition when they actually have another,” Dr. Blackshear said.

In his editorial, he noted that the new trials do not require proof that the patient has had venous thromboembolism that could be addressed by closure of the PFO, nor do the trials require trying anticoagulation drugs first.

“Thus, these trials will venture far beyond the current Food and Drug Administration-approved indication for PFO closure devices,” Dr. Blackshear wrote.

J.P. Mohr, M.D., at Columbia-Presbyterian Hospital in New York, who was not connected to this study, emphasized that the data are preliminary and the questions need further study.

“Many open-label trials like this looked great and were subsequently trumped by the results of a true randomized, in some cases double-blind, trial. This report does not even show superiority in the two-year time frame. Whether these findings would prompt support for a more controlled clinical trial is open to question,” Dr. Mohr said. “There is considerable consternation among investigators as to what role the PFO has in recurrence in a reasonable period of time such as two years. These data only unsettle the matter further, showing no striking benefit for closure and leaving unsettled the long-term effects.”