Although the study included more than 900 patients, some doctors say that researchers would need about 4,000 patients to draw significant conclusions on whether or not closing PFOs is an effective way to prevent recurrent strokes. The study also included patients who had other stroke risk factors, making it difficult to tell whether the PFO alone was the cause.
Some critics also say the STARFlex device used to close PFOs in the trial is inferior to other available devices. The STARFlex device is no longer available since its manufacturer, NMT Medical, went bankrupt in 2011.
Furlan, the lead author, didn't dispute the critics who called the CLOSURE trial flawed, but he said it is so far the best information available comparing the effectiveness of PFO closure to medication.
"Still, it's psychologically hard to say well, why not close the hole? Intuitively, that seems to make sense. But when you test it out, you have trouble finding the hard evidence," he said.
Many doctors frequently recommend closing PFOs in patients, saying the procedure is not only safe and effective, but also gives patients peace of mind that a potential problem is solved.
Melissa Smith, a 42 year-old mother of three, had her PFO closed while participating in the CLOSURE trial. Before the procedure, she had a mini-stroke that caused numbness on one side of her body. Her doctor discovered she had a PFO and told her it would put her at a higher risk for strokes in the future.
"The thought that something bigger could be lurking did make me feel unsure and anxious," Smith said.
Smith said she was relieved when one of her doctor's told her about the CLOSURE trial and that it was possible that she could have her PFO closed with a device that did not require open-heart surgery. "I knew [the device] was not FDA approved, but it was less invasive [than the alternative]."
Dr. Jonathan Tobis, director of interventional cardiology at the Ronald Reagan UCLA Medical Center and an investigator in upcoming trials studying PFOs, said that relieving a patient's fears about their heart is a major factor in his decisions to close PFOs. He said the outcome of the CLOSURE trial is not enough to dissuade him from closing PFOs in some of his patients.
"I'd still consider placing one just for the anxiety-lowering effect," Tobis said.
Currently, the U.S. Food and Drug Administration has not approved any device for closing PFOs, including the STAR Flex device used in the trial. But many doctors use devices off-label.
"During the 9 years it took for the results of this trial to be reported, approximately 80,000 patients have had a patent foramen ovale closed with the use of a device at an average cost of $10,000 per procedure, said Dr. Claiborne Johnston, of the Clinical and Translational Science Institute at the University of California, San Francisco, in an editorial published with the study.
Many doctors still say the results of the CLOSURE trial don't rule out closing PFOs. Doctors should assess each patient individually and determine the best option.
"Remember, the study does not say that medicines are better than closure; it says that they both prevent another stroke equally as well," said Dr. Rafael Gonzalez, division director of cardiology at Scott and White Hospital in Round Rock, Texas. "It leaves clinicians options on how best to treat the patients."
Two future trials are currently underway that will also compare PFO closure to medication therapy.