1. Patent Foramen Ovale Devices and Trials Update: Is the Current Data Sufficient for Approval? CRT Feb18-21, 2017
Steven L. Goldberg, MD
Medical Director, Structural Heart Program
Tyler Heart Institute
Community Hospital Monterey Peninsula
Chief Medical Officer, Cardiac Dimensions
Patent Foramen Ovale Devices and Trials Update: Is the Current Data Sufficient for Approval? 7 min

2. Steven Goldberg,MD Disclosure
Consultant (Proctor for Amplatzer devices)
St. Jude (now Abbott)
Investigator for RESPECT and PREMIUM randomized trials
Examples of relationships are: Advisory Board/Board Member, Consultant, Honoraria, Research Support, Speaker’s Bureau, Stockholder
Please list full company name

3. PFO Trials Update: Are Current Data Sufficient for Approval?
GOOD QUESTION!

4. PFO Trials Update: Are Current Data Sufficient for Approval?6
PFO Trials Update: Are Current Data Sufficient for Approval?
Probably Should!
Too much compelling evidence to throw it away

5. PFO Trials Update: Are Current Data Sufficient for Approval?7
PFO Trials Update: Are Current Data Sufficient for Approval?
Boo Yah!

7. Reduction in Ischemic Stroke RESPECT Primary Endpoint

8. Why this is important Why this is interesting
The FDA just approved a device that did not meet statistical significance in the pivotal trial primary endpoint!
WHY?
Why this is important Why this is interesting

9. Reduction in Ischemic Stroke RESPECT Primary Endpoint
Total 25 events (studied designed to stop when 25 events occurred)

10. Endpoints required for a large enough randomized trial – Yusuf and Peto
Yusuf, Collins and Peto Statistics in Medicine 1984 Vol 3:

11. Now with 5 year data Now with 46 events
(versus 25 for primary endpoint)
Thaler TCT 2016
Carroll TCT 2016

12. Potential for confounding considered Looking only at follow-up cryptogenic strokes

13. Indication for use
St. Jude Amplatzer PFO Occluder Device: Intended for percutaneous closure of a PFO to prevent recurrent ischemic stroke in patients who have had a cryptogenic stroke due to presumed paradoxical embolism

14. FDA statement from Bram Zuckerman
“But as the device labeling clearly states, patients need to be evaluated carefully by a neurologist and cardiologist to rule out other known causes of stroke and help ensure that PFO closure with the device is likely to assist in reducing the risk of recurrent stroke”

15. Neurology guidelines – July 2016
Need to be updated!

16. Patent Foramen Ovale Devices and Trials Update: Is the Current Data Sufficient for Approval?
This is no longer the question – it is approved
Which stroke patients should be considered?
Importantly, a second stroke is no longer required
Will the neurologists change their guidelines?
Will insurance pay?
Will the “team” approach catch on? Will insurance pay if patients are treated “off-label” (without documented approval by neurologist)
What about the role of PFO closure for migraines?

17. What about future studies? Gore REDUCE study
2:1 randomization device to medical management patients randomized (versus 980 in RESPECT)
Primary endpoints:
Reduction in clinical stroke after 2 years,
Reduction in new brain infarct (clinical plus silent stroke) through 2 years
2 year follow-up completion spring 2017
Smaller ”control” population will lead to lower events, however, including silent strokes will increase events

18. The FDA has done ”us” a solid (those caring for patients with PFO related conditions, and those patients)
Now it is up to “us” to be good stewards and treat our patients thoughtfully, carefully and RESPECTfully