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Patent Foramen Ovale and Aortic Arch Atheroma in Individuals with Stroke

5th Edition
2014 UPDATE
December 2014

The Canadian Stroke Best Practice Recommendations for the Secondary Prevention of Stroke, 5th Edition 2014 module is published in the International Journal of Stroke (IJS) (Online Open‑Access available December 2014; Printed Journal scheduled for April 2015).

To access the specific recommendations for Patent Foramen Ovale and Aortic Arch Atheroma in Individuals with Stroke and all other sections of the Secondary Prevention of Stroke module, please click on this URL which will take you to the recommendations online in the IJS:  http://onlinelibrary.wiley.com/doi/10.1111/ijs.12439/full. For the French version of these recommendations, open the appendix at this link : http://onlinelibrary.wiley.com/store/10.1111/ijs.12439/asset/supinfo/ijs12439-sup-0001-si.pdf?v=1&s=b0ed4fff1d7fc435cf4e2a83ccbcbffbdad767de.

All other supporting information, including performance measures, implementation resources, evidence summaries and references, remain available through www.strokebestpractices.ca, and not through the IJS.  Please click on the appropriate sections below for this additional content.

Rationale

While initial epidemiological studies suggest that patients with cryptogenic stroke, especially younger patients, are more likely to have a patent foramen ovale (PFO), there is controversy regarding the role of PFO in stroke etiology. PFO closure trials have not shown a reduction in stroke risk following device closure. There is lack of clear evidence to recommend the appropriate course of action for patients with unexplained stroke who are found to have a PFO.

System Implications
  • Support for ongoing research into etiology for patients with cryptogenic stroke.
  • Support for research to further investigate the impact of PFO closure versus medical therapy.

 

Performance Measures

Ongoing collection of epidemiological data on prevalence of PFO in individuals with stroke is recommended.

Implementation Resources and Knowledge Transfer Tools
Summary of the Evidence, Evidence Tables and References

PFO Evidence Tables and Reference List

The prevalence of patent foramen ovale (PFO), a small opening in the interatrial septum, is estimated to be 25%-30% in the general population and as high as 60% in patients with cryptogenic stroke (Riaz et al. 2013). Individuals with PFOs are at increased risk of stroke and stroke recurrence, particularly in younger patients (<60 years of age) with stroke of unknown etiology (Kernan et al. 2014).

Three RCTs (CLOSURE 1 [Furlan et al. 2012], the PC Trial [Meier et al. 2013], and RESPECT [Carroll et al. 2013]) have investigated the effectiveness of PFO closure in reducing the risk of stroke recurrence and mortality following cryptogenic stroke, compared to medical management. Each of the trials excluded patients who were more than 60 years of age whereas only the RESPECT trial excluded patients with TIAs. Across the three trials, no significant effects of treatment were reported for primary outcomes using intention-to-treat analyses. The associated hazard ratios (HR) were 0.78 (95% CI 0.45 to 1.35, p=0.37) in CLOSURE 1, 0.63 (95% CI 0.24 to 1.62, p=0.34) in the PC trial, and 0.49 (95% CI 0.22 to 1.11, p=0.08) in RESPECT (Furlan et al. 2012, Meier et al. 2013, Carroll et al. 2013). Whereas the authors of CLOSURE 1 and the PC trial both observed similar findings in per protocol based analyses, the authors of RESPECT reported that in a per protocol analysis PFO closure was associated with a significant reduction in the composite outcome of recurrent ischemic stroke or death, compared to medical therapy (HR= 0.37, 95% CI 0.14 to 0.96, p=0.03). The risk of serious adverse events was not increased significantly in the intervention arm of any of the trials.

In a meta-analysis that included results from all three RCTs, Spencer et al. (2014) reported that PFO closure was associated with a non-significant decrease in risk of stroke (RR=0.61, 95% CI 0.34 to 1.07) and TIA (RR 0.76, 95% CI 0.44 to 1.32), with an estimated decrease of 20 ischemic strokes and 6 TIAs per 1,000 persons treated over five-years. In another meta-analysis of the same 3 RCTs, Riaz et al. (2013) investigated the composite outcome of recurrent stroke or TIA and mortality over a mean follow-up time of 2.5 years and reported a non-significant trend in favor of PFO closure compared to medical therapy using an intention-to-treat analysis (HR 0.66, 95% CI 0.43 to 1.01, p=0.056), and a significant treatment effect in favour of PFO in the per protocol analysis (HR 0.64, 95% CI 0.41 to 0.98, p=0.04). The authors of both meta-analyses concluded that further research is required to determine if PFO closure is superior to medical management following cryptogenic stroke in younger individuals.