Abstract WMP110: Presence, Volume, and Location of New Ischemic Injury on MRI in Stroke Patients Who Undergo PFO Closure Compared to Patients Treated Medically: An Analysis of the REDUCE Trial

Abstract

Background: Randomized PFO closure trials have used open-label endpoint ascertainment, which may increase the risk of bias and undermine confidence in the conclusions. The Gore REDUCE Trial prospectively performed baseline and follow-up MRIs for all subjects, thereby providing an objective measure of the effectiveness of closure. Methods: The presence, location, and volume of new infarct, defined as an acute DWI lesion at time of recurrent clinical stroke or new lesion (>3mm) on T2/FLAIR from baseline to follow up MRI at 2 years, was evaluated using a semi-automated methodology blinded to treatment assignment, comparing patients randomized to undergo closure to those assigned medical therapy. Results: There were no differences in total new infarct volume, new large infarct (>3cm diameter), or new infarct location, comparing patients who underwent closure to those treated with medication (Table). New clinical stroke or clinically silent MRI infarct occurred in 18/383 (4.7%) patients who underwent closure and 19/177 (10.7%) of medically treated patients, RR 0.44, 95% CI 0.24-0.82, p=0.008. Recurrent clinical ischemic stroke occurred in 5/383 (1.3%) vs 12/177 (6.8%), RR 0.19, 95% CI 0.07-0.54, p=0.005, and silent brain infarction in 13/383 (3.3%) vs 7/177 (4.0%), RR 0.86, 95% CI 0.34-2.11, p=0.74. Conclusions: New MRI infarcts were generally small and the volumes and distribution of injury were similar between patients randomized to closure and those assigned to aspirin alone. The finding that silent infarcts were not smaller in volume than clinical ischemic strokes and that only clinical strokes were reduced by closure suggests that there may be ascertainment bias in clinical outcomes during open label studies. Nevertheless, as MRI is an objective outcome assessed blinded to randomization assignment, the REDUCE trial provides the highest level of evidence that PFO closure prevents recurrent ischemic brain injury, reducing new infarcts by more than half.