麻豆传媒

WASHINGTON -- Following FDA approval of the Amplatzer PFO Occluder device Friday, researchers released the final data from the RESPECT trial that had been requested by the agency as it weighed that decision.

Efficacy has been the key issue, questioned by the FDA's advisory panel and criticized by the (AAN) when it recommended against routine use earlier this year, but also one for which the evidence shifts with follow-up and endpoints definition.

In the final data with a mean 6 years of follow-up, RESPECT showed a 45% relative reduction in recurrent ischemic stroke -- 18 events versus 28 among the 980 patients, ages 18 to 60, at baseline with cryptogenic stroke and a patent foramen ovale (PFO), who were randomized to open-label to occlusion or medical management alone, respectively (P=0.046 in the intent-to-treat analysis).

As in prior years' follow-up, the more narrowly defined the patient population or stroke endpoint, the better the device looked. Censoring patients at age 60 boosted the relative risk reduction to 58%. For freedom from recurrent ischemic stroke of unknown origin, the risk reduction was a relative 62%, , of Tufts Medical Center in Boston, reported at the Transcatheter Cardiovascular Therapeutics (TCT) annual meeting.

The device, in the end, was approved to reduce stroke risk for patients with prior cryptogenic stroke believed to be caused by a PFO-related blood clot.

"PFO-closure cannot prevent strokes from non-PFO-related causes," Thaler said at a TCT press conference for the late-breaking clinical trials session. But he emphasized, "Collaboration between a cardiologist and neurologist is important for proper patient selection."

The neurology association's rejection of routine PFO closure was premature, Thaler argued. "The American Academy of Neurology published in the summer. It came just after the May panel meeting and came out without the benefit of the data that were presented at the May panel meeting. The moment those guidelines hit the press, they were out of date. I have a problem with that."

The Kaplan-Meier curves looked like they were separating out, then coming together at 5 years, then separating again with longer follow-up, noted press conference moderator , of Mount Sinai Medical Center in New York City. "They, I think, may have contributed to the uneven report of the data," he said. "They weren't so steady, the results of this paper."

At least some neurologists appear to be holding off on PFO closure referrals.

, of Cedars-Sinai Medical Center in Los Angeles, told 麻豆传媒 at the time of the AAN guideline release: "Here is how I explain it to patients: we have two studies in favor and two studies against PFO closure. Let's wait for the 'tie breaker' study to finish before we decide to close your PFO."

That tie-breaker could be the of the Gore Helex Septal Occluder for recurrent stroke prevention, due out in the next year or so.

At that point, "the neurology community will have to recognize that these are data," Thaler said. "Opinions are opinions, but data are data. People can't argue with that."

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