Results Summary

What was the research about?

A patent foramen ovale, or PFO, is a small hole between the top two chambers of the heart that didn’t close correctly after birth. PFOs can raise the risk for stroke. For adults ages 18–60, about 10 percent of strokes caused by a blocked artery are related to a PFO. Among these patients, questions remain about what treatment works best to prevent future strokes.

In this study, the research team analyzed data from six clinical trials to compare two treatments for preventing future strokes among patients who had experienced a PFO-related stroke:

  • Medicines alone. Patients take medicines to prevent blood clots.
  • Surgical procedure to close the PFO, plus medicines. A doctor inserts a medical device through a vein to the PFO. The device closes the PFO and remains in the heart permanently. Patients also take medicines to prevent blood clots.

The research team looked at the risk of future strokes and at safety risks like serious adverse events. A serious adverse event occurs when medical care causes harm, such as having bleeding when taking blood thinners. The team also looked at treatment effects based on how likely it was that the PFO caused patients’ strokes. To determine likelihood, the team used existing scoring systems.

What were the results?

Compared with patients who took medicines alone, patients who also had surgery had a lower risk of future strokes.

Patients whose PFO was likely the cause of their stroke had a lower risk of future strokes with surgery plus medicines than with medicine alone, compared with patients whose PFO was not likely the cause of their stroke, based on the scoring systems.

Patients who had surgery had a higher risk of irregular heartbeat events within 45 days of surgery. But most patients’ heartbeats went back to normal over time. Other safety outcomes like bleeding or blood clots didn’t differ between the two treatments.

Who was in the study?

The study included data from 3,740 patients across six trials. The trials took place around the world from 2000 to 2017. Patients in the trials were ages 18 and older and had experienced a PFO-related stroke. The average age was 46, and 55 percent were men.

What did the research team do?

The research team combined and analyzed data from the six trials. The trials included patients with a PFO who had a stroke. Combining data from multiple trials provides more reliable results than data from single trials.

Researchers from the six trials provided input during this study.

What were the limits of the study?

The study couldn’t look at whether another stroke caused more disability, because some kinds of data were missing, such as how much help people needed at home.

Future research could compare how different medicines and types of medical devices reduce patients’ risk of having a stroke.

How can people use the results?

Patients who had a PFO-related stroke and their doctors can use these results when considering treatments for preventing future strokes.

Final Research Report

View this project's final research report.

Peer-Review Summary

Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.

The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments. 

Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following:

  • The reviewers lauded the researchers for completing this individual patient data meta-analysis of stroke treatment studies designed to optimize selection of therapies to prevent recurrent stroke events. There were no significant concerns.
  • The reviewers did ask why the researchers established a score of 7 to delineate high and low probability of the reason for a stroke on the Risk of Paradoxical Embolism (RoPE) score. The researchers explained that 7 was the median score in the original database of patients, although they acknowledged that RoPE scores for patients in randomized clinical trials were lower than 7. The researchers explained that patients with RoPE scores below 7 showed less evident benefit from antithrombotic therapy.
  • The reviewers asked why the researchers did not explore treatment response heterogeneity based on different antithrombotic treatments. The researchers explained that most of the studies they exampled did not randomize patients to specific antithrombotic therapies, resulting in the potential for unmeasured confounding in a treatment response heterogeneity analysis.

Conflict of Interest Disclosures

Project Information

David M. Kent, MD, MS
Tufts Medical Center Inc.
The Systematic , Collaborative, PFO Closure Evaluation (SCOPE)

Key Dates

March 2023


Has Results
Award Type
State State The state where the project originates, or where the primary institution or organization is located. View Glossary
Last updated: April 26, 2023