May 30, 2013
At the large clinical trials sessions at the ESC today there were back to back presentations from the Percutaneous Closure of Patent Foramen Ovale in Cryptogenic Embolism (PC) trial by Prof. Mattle and the Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment (RESPECT) trial by Prof. Saver. These two clinical trials randomized patients with cryptogenic stroke and patent foramen ovale to percutaneous closure using the Amplatzer PFO occluder device or medical therapy. The Aplatzer device is one of three devices tested in clinical trials of PFO occlusion, the others being the STARflex, and cardioSEAL. The STARflex was the device used in the Closure or Medical Therapy for Cryptogenic Stroke With Patent Foramen Ovale (CLOSURE) and was found to be associated with high rates of device thrombosis and atrial fibrillation.
The presentation by the PC trialists focussed on the analysis of stroke events in addition to the overall events in the primary intention-to-treat analysis. They presented an 80% relative risk reduction on stroke in the device group, but nowhere near the number of subjects enrolled needed to achieve statistical significant. The device seemed to be relatively safe.
The RESPECT presentation focussed on the “device in place” analysis which moved a 3 of the stroke outcome events in the group randomized to device moved over to the medical (i.e. device not in place group). These three strokes occurred in a subject who changed his mind about having the PFO closed, one who was waiting for the procedure and one who had coronary artery disease and needed CABG surgery. This analysis demonstrated a benefit of PFO closure which, unlike the intention to treat analysis, was statistically significant. The trialists concluded that the “device in place” analysis confirms the biological effect of PFO closure for cryptogenic stroke.
Of note was an analysis combining the two studies (PC + RESPECT) shown by Prof. Mattle demonstrating a statistically significant reduction in stroke with PFO occlusion. This is what happens when two clinical trials show a non-statistically significant benefit in reduction of stroke with PFO occlusion are combined.
PFO occlusion with the Amplatzer device is safe and probably effective in preventing stroke in those cases with true cryptogenic stroke. The problem with closure of PFO in cryptogenic stroke is the low rate of recurrent stroke in general in this population and the fact that there are other effective interventions for preventing stroke: diet, lifestyle, and aggressive risk reduction. When a 45 year-old borderline hypertensive patient who is overweight and does not exercise presents with a “cryptogenic” stroke and is found to have a PFO should it be occluded? How about starting low-dose aspirin and intensive lifestyle changes aimed at moderate weight loss and achieving 40 minutes of exercise 5 days a week? It seems much easier to just close the PFO, but that may not be the right thing to do.