Pills vs PFO Closure in Stroke Prevention

Hans-Christoph Diener, MD, PhD


December 19, 2012

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Dear colleagues, my name is Christoph Diener. I am a neurologist from the Department of Neurology and Stroke Center at the University of Essen in Germany. Today's topic is cryptogenic stroke and patent foramen ovale (PFO).

You know that 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, we could not find a cause for the stroke. Now there is evidence from epidemiologic data that these patients have a higher prevalence of PFO. 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.[1] This trial was clearly negative, meaning that PFO closure was not superior to treatment with aspirin and warfarin.

At the Transcatheter Cardiovascular Therapeutics (TCT) 2012 conference, the RESPECT trial was presented.[2] It 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. Inclusion criteria were patients between 18 and 60 years of age who had a cryptogenic stroke within the last 270 days. 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.

If we look at the technical success rate, it was great. It was 96%. Let's look at the primary endpoint. 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 is the interpretation? Technically, this is a neutral trial. At the conference, there was another trial presented from Europe[3] that was also neutral in terms of the primary endpoint.

The main argument was always to prevent patients from taking warfarin long-term and to avoid bleeding, but obviously, antiplatelet drugs are as effective as warfarin. I think these patients should first be treated with aspirin, and only if they have a recurrent event should one consider PFO closure.

Ladies and gentlemen, we now have evidence from 3 randomized trials on PFO closure in cryptogenic stroke, which is really great. My name is Christoph Diener, a neurologist at the University of Essen. Thank you very much for listening.