Department of Neurology (S.R.M., S.E.K.), University of Pennsylvania, Philadelphia.
Department of Radiology (G.E., M.B., C.D.), University of Pennsylvania, Philadelphia.
Stroke. 2021 Nov;52(11):3419-3426. doi: 10.1161/STROKEAHA.121.034451. Epub 2021 Aug 30.
Randomized patent foramen ovale closure trials have used open-label end point ascertainment which increases the risk of bias and undermines confidence in the conclusions. The Gore REDUCE trial prospectively performed baseline and follow-up magnetic resonance imaging (MRIs) for all subjects providing an objective measure of the effectiveness of closure.
We performed blinded evaluations of the presence, location, and volume of new infarct on diffusion-weighted imaging of recurrent clinical stroke or new infarct (>3 mm) on T2/fluid attenuated inversion recovery from baseline to follow-up MRI at 2 years, comparing closure to medical therapy alone. We also examined the effect of shunt size and the development of atrial fibrillation on infarct burden at follow-up.
At follow-up, new clinical stroke or silent MRI infarct occurred in 18/383 (4.7%) patients who underwent closure and 19/177 (10.7%) medication-only patients (relative risk, 0.44 [95% CI, 0.24–0.81], P=0.02). Clinical strokes were less common in closure patients compared with medically treated patients, 5 (1.3%) versus 12 (6.8%), P=0.001, while silent MRI infarcts were similar, 13 (3.4%) versus 7 (4.0%), P=0.81. There were no differences in number, volumes, and distribution of new infarct comparing closure patients to those treated with medication alone. There were also no differences of number, volumes, and distribution comparing silent infarcts to clinical strokes. Infarct burden was also similar for patients who developed atrial fibrillation and for those with large shunts.
The REDUCE trial demonstrates that patent foramen ovale closure prevents recurrent brain infarction based on the objective outcome of new infarcts on MRI. Only clinical strokes were reduced by closure while silent infarctions were similar between study arms, and there were no differences in infarct volume or location comparing silent infarcts to clinical strokes.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT00738894.
随机开放标签终点评估的卵圆孔未闭封堵试验增加了偏倚风险，削弱了对试验结论的信心。戈尔 REDUCE 试验前瞻性地对所有患者进行了基线和随访磁共振成像（MRI），提供了一种对封堵有效性的客观测量方法。
我们对基线至 2 年随访 MRI 上出现的新发临床卒中或新的（>3mm）T2/液体衰减反转恢复高信号区的弥散加权成像上的新梗死进行了盲法评估，比较了封堵与单纯药物治疗的效果。我们还检查了分流大小和房颤的发展对随访时梗死负荷的影响。
在随访时，18/383（4.7%）接受封堵治疗的患者和 19/177（10.7%）仅接受药物治疗的患者发生新的临床卒中或无症状 MRI 梗死（相对风险，0.44[95%可信区间，0.24-0.81]，P=0.02）。与接受药物治疗的患者相比，封堵患者的临床卒中发生率较低，分别为 5 例（1.3%）和 12 例（6.8%）（P=0.001），而无症状 MRI 梗死的发生率相似，分别为 13 例（3.4%）和 7 例（4.0%）（P=0.81）。与单纯药物治疗的患者相比，封堵患者新发梗死的数量、体积和分布无差异。无症状梗死与临床卒中相比，也没有数量、体积和分布的差异。在发生房颤和分流较大的患者中，梗死负荷也相似。
REDUCE 试验表明，卵圆孔未闭封堵可以通过 MRI 上新梗死的客观结果预防复发性脑梗死。只有临床卒中的发生率因封堵而降低，而研究臂之间的无症状梗死相似，无症状梗死与临床卒中相比，梗死体积或位置没有差异。
