A catheter procedure that closes a hole in patients’ hearts is no more effective than medical therapy in preventing recurrent strokes, according to a new study published in the 15 March issue of The New England Journal of Medicine.
In the CLOSURE I trial, clinical researchers compared a catheter procedure plus medical therapy with medications alone to prevent new strokes or transient ischaemic attacks in patients between 18 and 60 years old with a cryptogenic stroke or transient ischaemic attack and a patent foremen ovale (PFO).
In the ground-breaking, international multi-site study led by University Hospitals Case Medical Center and Case Western Reserve University School of Medicine, researchers sought to demonstrate the superiority of the STARFlex Septal Closure System (NMT Medical/Gore) over medical therapies (aspirin or warfarin) alone. Instead, results showed no statistically significant differences between the two therapies.
“These important findings will serve as a guidepost in the prevention of stroke in patients with PFO,” said Anthony J Furlan, lead investigator of the study and Chairman of the Department of Neurology at UH Case Medical Center and Case Western Reserve University School of Medicine.
In an accompanying editorial, S Claiborne Johnston, from the University of California, San Francisco, wrote, “…CLOSURE I provides the best evidence available regarding the role of closure in stroke prevention and should not be ignored. The results of the trial do not support closure of a patent foramen ovale to prevent stroke in patients who have had a stroke or a transient ischaemic attack of unclear etiology.”
The editorial also notes that it took nine years for the results of this trial to be reported and during that time, approximately 80,000 patients have had a PFO closed with the use of a device at an average cost of US$10,000 per procedure. “Even if only half these patients were treated by this method for the purpose of preventing stroke, it would suggest that during that period of time US$400 million was spent on a procedure that had no apparent benefit, to say nothing of the potential clinical risks involved,” wrote Johnston.
CLOSURE I is the first completed prospective, randomised, two-arm superiority trial of percutaneous PFO device closure versus medical therapy alone in cryptogenic stroke patients using the STARFlex Septal Closure System. The device, attached to a catheter and threaded into the upper heart, applies a “clamshell” patch on both sides of the hole.
The trial’s primary endpoint was the difference in the stroke and transient ischaemic attack rates between the two patient groups at two years, death from all causes in the first 30 days, and death from neurological causes at 30 days or more.
Furlan and colleagues enrolled 909 patients at 87 United States and Canadian sites during 64 months ending October 2008. Researchers randomised patients to either medical therapy (325mg of aspirin or the appropriate warfarin dose, or a combination of both) or PFO closure and medical therapy (75mg of clopidogrel for six months and 325mg of aspirin for two years).
“Based on the trial results, even though a patient had a PFO and a recurrent stroke, the hole may be totally coincidental to the second stroke,” Furlan said. “The undeniable message here is that too many of these holes are being closed with an off-label procedure, but partly that is because we have never had a randomised trial to guide us. Furthermore, our criteria for diagnosing paradoxical embolism and the potential efficacy of PFO closure in patient subgroups require further study. Until then we would advise initial secondary stroke prevention with medical therapy in most patients with unexplained stroke or transient ischaemic attack and a PFO.”