LONDON, United Kingdom — A post hoc "device in place" analysis of a trial of patent foramen ovale (PFO) closure in the secondary prevention of stroke has shown a magnification of benefits in comparison with the intention-to-treat or per-protocol analyses presented previously.
The latest analysis from the Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment (RESPECT), which considers only patients who actually had the PFO closure device fitted as being in the active treatment group, was presented at the XXII European Stroke Conference (ESC) 2013.
"The magnification of benefit seen in this analysis is what would be expected if the device was exerting a biological effect," said Jeffrey Saver, MD, University of California, Los Angeles, reporting these latest data.
The RESPECT trial included 980 patients who had sustained a previous cryptogenic stroke and had a PFO. They were randomly assigned to PFO closure with the Amplatzer (St Jude Medical) device or to medical treatment. The main results, published in the New England Journal of Medicine earlier this year and reported by Medscape Medical News at that time, showed a nonsignificant difference in the primary endpoint (death or recurrent stroke) in the intention-to-treat analysis but a significant reduction in the per-protocol analysis with the closure device.
An editorial accompanying the publication of the main results suggested that the data were not strong enough to advocate routine PFO closure in patients who had had a cryptogenic stroke.
Dr. Saver explained to Medscape Medical News that for the current "device in place" analysis, 24 patients who were randomly assigned to the device group but who did not actually receive the device are now considered as being in the medical treatment group.
Three of these patients had a stroke. "So instead of there being 16 events in the medical arm versus 9 in the device arm as in the intention-to-treat analysis, the 'device in place' analysis has 19 events in the medical arm versus 6 in the device group."
This gave a 70% risk reduction, with a P value of .006. "This makes a big difference to the results, substantially magnifying the benefit of the device," Dr. Saver commented.
"When you do this type of analysis you are removing some of the noise that happens by chance, and if the treatment is working, the effect should be magnified. This is exactly what we see," he added. "These results provide further evidence that there is a genuine biologic effect. The device gives a modest but real benefit over medical therapy. The event rates in this trial were low so it is challenging for the device to demonstrate superiority. It has to be extremely effective and safe to do so."
Dr. Saver cautioned, however, that this "device in place" analysis can only be considered exploratory because this type of analysis can sometimes overestimate the treatment effect.
A second smaller trial of the Amplatzer device in this indication, the Clinical Trial Comparing Percutaneous Closure of the Patent Foramen Ovale Using the Amplatzer PFO Occluder with Medical Treatment in Patients with Cryptogenic Embolism (the PC trial), published in the same issue of the New England Journal of Medicine as RESPECT, has shown similar results.
Dr. Saver said that an individual-patient meta-analysis of the 2 trials is now planned.
The PC and RESPECT studies were sponsored by St Jude Medical.
XXII European Stroke Conference (ESC). Large Clinical Trials B; 2. Presented May 30, 2013.
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Cite this: RESPECT 'Device in Place' Analysis: Benefits of PFO Closure? - Medscape - Jun 25, 2013.