Percutaneous PFO closure was no more effective than standard therapy in the prevention of recurrent stroke, according to results of the CLOSURE I trial presented in Chicago at the American Heart Association.
In CLOSURE I 909 patients were randomized to either medical therapy or PFO closure with the STARFlex Septal Closure System followed by subsequent medical therapy. There was no significant difference in the primary endpoint (the rate of stroke and TIA at 2 years) between the two groups (5.5% in the PFO-treatment group versus 7.7% in the control group). Stroke recurrence at two years was 3% in both groups.
“Based on the trial results, even though a patient has a PFO and a recurrent stroke, the hole may be totally coincidental to the second stroke,” said Anthony Furlan, lead investigator of the study, in an AHA press release. “The undeniable message here is that too many of these holes are being closed with an off-label procedure, but that’s partly because we’ve never had a randomized trial to guide us.”
Here is the AHA press release:
- A special catheter procedure to close a patent foramen ovale (PFO) – a hole between the chambers of the heart –was not significantly better than drug therapy in preventing another stroke in patients whose initial stroke had no other identifiable cause.
- A PFO is a congenital defect that’s often closed to help prevent another stroke.
- Researchers said their findings suggest physicians may perform too many PFO closure operations.
CHICAGO, Nov. 15, 2010 – A catheter procedure that closes a hole in patients’ hearts appears to be no more effective than drug therapy in preventing recurrent strokes, according to late-breaking clinical trial results presented at the American Heart Association’s Scientific Sessions 2010.
In the CLOSURE I trial, researchers compared a catheter procedure plus medical therapy with medications alone to prevent new strokes or transient ischemic attacks (TIAs) in patients with unexplained stroke or TIA and a patent foremen ovale (PFO) – a hole between the heart’s two upper chambers.
Researchers sought to demonstrate the superiority of the STARFlex® Septal Closure System followed by clopidogrel over drug therapies (aspirin or warfarin or both) alone. Instead, results showed no statistically significant differences between the two approaches to therapy.
“It is possible the procedure has a slight benefit, but you would need thousands of patients to find it in a randomized trial,” said Anthony J. Furlan, M.D., lead investigator of the study and chairman of the neurology department at the Case Western Reserve University School of Medicine and University Hospitals Case Medical Center in Cleveland, Ohio.
Strokes of unknown origin – cryptogenic strokes – have several causes, including PFO, a hole between the heart’s two upper chambers that’s vital to fetal survival, but is abnormal if it doesn’t close completely after birth. If a blood clot develops in a vein, passes through the hole and reaches the brain – called a paradoxical embolism – a stroke results.
“In roughly 20 percent of adults, remnants of the hole persist,” Furlan said.
No medical device is approved by the Federal Drug Administration for sealing PFOs. However, physicians use devices approved for closing other types of heart holes to seal the opening between the right and left atria, usually in hopes of preventing a stroke.
CLOSURE I is the first completed prospective, randomized, two-arm superiority trial comparing percutaneous device PFO closure to medical therapy 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”-type patch on both sides of the hole.
The trial’s primary endpoint was the difference in stroke and TIA 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 over 64 months ending October 2008. Study members were 60 years old and younger with an average age of 47. Researchers randomized patients to either medical therapy (325 mg of aspirin or the appropriate warfarin dose, or a combination of both) or PFO closure with subsequent medical therapy (75 mg of clopidogrel for six months and 325 mg of aspirin for two years).
The study found percutaneous closure with STARFlex® plus medical therapy did not offer any significant benefit over medical therapy alone. There was slight, although not statistically significant decrease in the primary endpoint for the PFO-treatment group (5.5 percent) versus the medical therapy group (7.7 percent). Two-year stroke recurrence rate was identical in both groups (3 percent) and researchers found no difference in outcomes between patients treated with aspirin versus warfarin, although Furlan noted the trial was not powered to determine the best medical therapy.
He said possible alternative explanations for the strokes and TIAs that occurred were found for 22 of 29 patients in the medication-only group and in 20 of 23 of the PFO-closure patients. The causes included a blood clot in the left atrium and new atrial fibrillation (an irregular heartbeat).
“Based on the trial results, even though a patient has 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 that’s partly because we’ve never had a randomized trial to guide us.”
He said the criteria for diagnosing paradoxical embolism and the potential efficacy of PFO closure in patient subgroups requires further study.
Co-authors are Mark Reisman, M.D.; Joseph Massaro, Ph.D.; Laura Mauri, M.D.; Harold Adams, M.D.; Gregory Albers, M.D.; Robert Felberg, M.D.; Howard Herrmann, M.D.; Saibal Kar, M.D.; Michael
Landzberg, M.D.; Albert Raizner, M.D.; and Lawrence Wechsler, M.D. Author disclosures are on the abstract.
NMT Medical funded the study.