St. Jude Medical Inc.’s device to plug openings in the heart after a stroke failed to definitively prevent repeat incidents in patients under age 60 compared with non-surgical drug treatment, two studies found.
The data calls into question broader use of the procedure and the product, used for nearly two decades at a cost of about $20,000 for each of about 9,000 surgeries done yearly.
Neither study determined that St. Jude’s Amplatzer PFO Occluder significantly reduced risk of a second stroke. One, funded by the St. Paul Minnesota-based company, found the device was beneficial once researchers adjusted the data to consider different dropout rates and types of treatment. The twin reports suggest the surgery isn’t a panacea for those who inexplicably suffer a stroke, and then must rely on lifelong use of blood thinners to avoid another one, doctors said.
“If there is a huge treatment effect, none of these trials have been able to show it,” said Deepak Bhatt, chief of cardiology at the VA Boston Healthcare System and a professor at Harvard Medical School, in an interview.
The studies were presented independently today at the Transcatheter Cardiovascular Therapeutics conference in Miami. St. Jude fell 3.6 percent to $38.27 at the close in New York. The company has gained 12 percent this year.
The St. Jude plug, made up of two wire-mesh discs filled with a polyester fabric, is threaded into the heart via a vein in the leg, and clamped like a cuff-link through the hole. In the U.S., about 40,000 people would be potential candidates if the results were positive, said Larry Biegelsen, an analyst at Wells Fargo Securities in New York.
“We need a definitive trial of this approach if it’s going to be broadly used for PFO closure,” Bhatt said in an interview at the meeting. “Anecdotally, there are patients who seem to benefit. It’s unfortunate that none of the trials have been able to absolutely nail that down.”
The Amplatzer plug device generates less than $100 million a year. The potential market for the heart closure device to prevent strokes is about $400 million, Biegelsen wrote in a Sept. 24 note to investors.
St. Jude will file for U.S. Food and Drug Administration approval of the device in the next month or two, said Glenn Novarro, an analyst for RBC Capital Markets in New York.
“Investors should assume the product will not receive FDA approval” and consider it an upside surprise if the device gets clearance in the next year, he said in an interview. “Everyone expected positive news. You can’t be optimistic today given that the primary endpoint missed.”
The results won’t change medical practice very much, with some high-risk patients still likely to get treated even without formal FDA approval, Ajay Kirtane, director of the interventional cardiology fellowship program at Columbia University Medical Center/New York-Presbyterian Hospital in New York, said at the meeting.
“I would like as a physician to have the option to discuss it with the patient and be able to use it if the patient elects to do so,” he said. “That would be the ideal scenario. To use it in everybody, I don’t think you can do that on the basis of this data.”
The Respect trial funded by St. Jude tracked 980 patients ages 18 to 60. It started in 2003 and ran until there were 25 strokes recorded. There were no deaths or fatal strokes, with non-fatal strokes occurring in 9 patients assigned to the Amplatzer plug and 16 patients slated to get medicine.
Intent to Treat
The difference wasn’t significant in a so-called intent to treat analysis, the standard method required by U.S. regulators. Three of the nine strokes in the Amplatzer group occurred in patients who actually never received the device. Patients had a stroke before it was implanted, underwent open heart surgery to repair the hole or elected not to get the procedure after being assigned to the Amplatzer group. Based on clinical trial design, they were still counted against the device.
Removing those patients from the Amplatzer arm, and adjusting the drug therapy group for example when a patient stopped blood thinners so they could have surgery, there was a significant 63 percent lower stroke risk in the Amplatzer arm.
“These are healthy people, and the results are something a 46-year-old stroke patient wants to know,” said lead researcher John Carroll, director of interventional cardiology at the University of Colorado. “It works. What we are debating is how superior it is to medical therapy. Any benefit that could potentially cut the risks down the road has a big impact.”
Two Amplatzer patients in the study developed cardiac tamponade, when blood or fluid builds up around the heart. Two others developed a clot in the heart around the time of the procedure, Carroll said. There was no evidence of clots forming around the device or signs of erratic heart rates.
The second study, known as the PC Trial, also didn’t find patients treated with the device fared significantly better. The trial followed 414 patients enrolled in Europe, Brazil, Canada and Australia starting more than a decade ago.
Differences in a composite goal of reducing deaths, non-fatal stroke, transient ischemic attack or peripheral embolism weren’t significantly different between the two groups, the study found. When the researchers looked only at stroke risk, they also uncovered no definitive difference.
The study was initially funded with a grant from St. Jude and conducted independently.
“The good news for patients is that the event rate is very low and both options are reasonable,” said Anil Poulose, an interventional cardiologist at Minneapolis Heart Institute at Abbott Northwestern Hospital. “Initially there was a lot of enthusiasm that we could cut the event rate dramatically. That has died down.”