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Patent foramen ovale closure or medical therapy for cryptogenic ischemic stroke: an updated meta-analysis of randomized controlled trials

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Abstract

Background

Previous randomized controlled trials (RCT) failed to demonstrate benefits of patent foramen ovale (PFO) closure (PFO-C) over medical therapy (MT) for secondary prevention of cryptogenic ischemic stroke. Three recently published RCTs, however, turned out positive for PFO-C and warrant an updated meta-analysis.

Methods

Data from all available RCTs on PFO-C vs. MT for secondary prevention of cryptogenic ischemic stroke up until October 2017 were abstracted and analyzed in a comprehensive meta-analysis. Clinical efficacy outcomes were recurrent stroke, recurrent TIA, and their combination; safety outcomes were mortality, major bleeding, venous thromboembolism (VTE), and new-onset atrial fibrillation/flutter (NOAF).

Results

Five trials including a total of 3440 patients were included in the meta-analysis. PFO-C significantly reduced recurrent stroke [odds ratio (OR) 0.41, 95% confidence interval (CI) 0.19–0.90; p = 0.03] and the combination of recurrent stroke + TIA (OR 0.53, CI 0.36–0.80; p = 0.002) compared to MT; recurrent TIA alone showed no differences (OR 0.77; CI 0.51–1.14; p = 0.19). NOAF was significantly more frequent after PFO-C (OR 5.75, CI 3.09–10.70; p < 0.00001). Mortality (OR 0.80, CI 0.39–1.67), major bleeding (OR 0.96, CI 0.48–1.92), and VTE (OR 2.45, CI 0.75–7.99) remained neutral. Trials with superior patient selection for PFO-C showed advantageous results compared to MT.

Conclusions

PFO-C after cryptogenic ischemic stroke is safe and effective to reduce the risk of recurrent stroke and recurrent stroke + TIA, albeit with an increased risk for NOAF.

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Funding

None of the authors received third-party funding for this work. Design, conduct and reporting are thus free from financial influence.

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Authors and Affiliations

  1. Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University, Moorenstr. 5, 40225, Düsseldorf, Germany

    Volker Schulze, Yingfeng Lin, Athanasios Karathanos, Maximilian Brockmeyer, Tobias Zeus, Amin Polzin, Stefan Perings, Malte Kelm & Georg Wolff

  2. Cardiovascular Research Institute Düsseldorf (CARID), Düsseldorf, Germany

    Malte Kelm

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  1. Volker Schulze
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Contributions

VS and GW conceived and designed the study. VS, YL, MB, AK and GW collected sources, selected studies, abstracted data and performed double checks. All authors analyzed and interpreted the data. GW and VS performed the statistical analyses and drafted the manuscript, all authors critically revised the manuscript. All authors read and accepted the submitted version of the manuscript.

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Correspondence to Georg Wolff.

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Conflict of interest

Neither was any of the investigators personally involved in any of the included trials, nor had any of the investigators a conflict of interest on the subject.

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Schulze, V., Lin, Y., Karathanos, A. et al. Patent foramen ovale closure or medical therapy for cryptogenic ischemic stroke: an updated meta-analysis of randomized controlled trials. Clin Res Cardiol 107, 745–755 (2018). https://doi.org/10.1007/s00392-018-1224-4

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