What is a cryptogenic stroke?
A considerable number of younger people who have an ischemic stroke before the age of 60 have what is called a cryptogenic stroke, meaning that at evaluation, a cause for the stroke could not be found. There is evidence from epidemiological data that these patients have a higher prevalence of PFO (50-60%). The assumed mechanism of action for stroke in this patient is paradoxical embolism. There is a trial that looked at PFO closure with transcutaneous devices, the so-called CLOSURE trial. This trial was negative, meaning that PFO closure was not superior to treatment with aspirin and warfarin.
More Information on cryptogenic stroke and PFO Closure from Industry
At the Transcatheter Cardiovascular Therapeutics (TCT) 2012 conference, the RESPECT trial was presented. This trial was supported by St. Jude and the trial was performed at 69 sites in the United States and Canada. The Amplatzer™ PFO occluder was used.
Patients between 18 and 60 years of age who had a cryptogenic stroke within the last 270 days.
PFO Closure Study Design:
Patients were randomly assigned to either occlusion of the PFO or medical treatment with antiplatelet drugs or warfarin. The primary endpoint was nonfatal recurrent stroke, fatal recurrent stroke, and early death after randomization. In this trial, 499 patients were randomized to PFO occlusion and 464 were occluded; 481 patients received medical treatment. On average, the patients were 46 years old and they were followed for about 2.5 years.
The PFO Closure Data
Technical success rate was great at 96%.
PFO Closure Primary End Point:
The primary endpoint occurred in 9 patients in the PFO occlusion group and in 16 in the medical treatment group. This relates to a relative risk reduction of 46%, which was not statistically significant. In the per-protocol analysis, 6 patients with PFO closure and 14 on medical treatment reached the primary endpoint, and this difference was statistically significant. If we calculate this into numbers needed to treat for 5 years, it would be 24 patients who would have to be treated to prevent 1 endpoint, particularly major stroke.
What does it mean?
Technically, this is a neutral trial. At the 2112 conference, there was another trial presented from Europe (PC) that was also neutral in terms of the primary endpoint.
The main argument for PFO Closure was always to prevent patients from taking warfarin long-term and to avoid bleeding and reduce the risk of further strokes. Now the stroke / PFO closure debate has tipped back to the decision that these patients should first be treated with blood thinning/coumadin/aspirin, and only if they have a recurrent event should one consider PFO closure. See more on the cryptogenic stroke and pfo closure argument here….