Sobering reminder: just because it is intuitively obvious doesn’t mean it’s true

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The following is a guest post written by Harold DeMonaco, one of our expert editors on, and Director of the Innovation Support Center at the Massachusetts General Hospital.


The March 15 2012 issue of the New England Journal of Medicine includes the results of a nine year study for stroke prevention that received very little attention from mainstream news organizations.

Given some of the health care research news that has garnered news attention, I have to wonder what other journalists and editors were thinking about.

A significant number of patients who suffer a stroke do so for no apparent reason.  No cause can be identified in up to 40% of those patients.  There is good evidence that a significant number of these strokes are casued by a common heart defect, called patent foramen ovale (PFO).  About 25% of presumably healthy people have a PFO (an opening between the right and left atria or upper chambers in the heart).  All of us are born with a PFO.  It allows blood to bypass the lungs in the fetus since oxygen is supplied by the mother’s blood circulation.  The PFO closes in most right after birth.

In theory, blood clots can travel from the right side of the heart and into the left ventricle and then be carried to the brain causing the stroke.  Based on a number of reported case studies and small open label trials, a number of academic medical centers began to provide a new catheter based treatment.  The treatment consists of placement of a closure device into the heart through the veins and serves to seal the opening.  The procedure looks much like a cardiac catheterization.  There are at least three medical devices used during this procedure; the Amplatzer PFO occluder, the Gore Helix Septal Occluder and the Starflex Septal Repair Implant.

The industry sponsored study reported this week looked at two approaches to managing people who have had a previous cryptogenic stroke: 462 had medical care consisting of warfarin, aspirin or both for two years.  447 had placement of a Starflex Implant along with clopidogrel for 6 months and aspirin for two years.  All subjects were randomized to the treatment arms.  At the end of two years, 2.9% of the PFO closure group suffered another stroke compared to 3.1% of the people treated with drugs alone.  Basically no difference in stroke outcome.

Overall, adverse events were equal in both groups with those having the device implanted suffering more events directly related to its placement.

This study is important from a number of perspectives.  The use of a medical device to prevent recurrent stroke is an appealing option.  The underlying assumption that the PFO was the root cause of the cryptogenic stroke suffered by the enrollees seems reasonable and supported by a good deal of prior studies.  Open label trials demonstrated apparent success.  And, just about every major medical center in the US offers the procedure.  While there are several limitations to the study published this week, the editorial comment accompanying the article is entitled, “Patent Foramen Ovale Closure — Closing the Door Except for Trials.  It took a randomized clinical trial to strongly suggest that the apparent benefit of a PFO closure over medical therapy was not well founded.  Other devices may fare better when studied head to head with medical therapy alone.  There may well be a subpopulation of stroke patients who could benefit from the placement of a closure device.  But this remains to be seen.

The study took 9 years to complete.  A major reason for delay in completion was the inability of many centers to enroll patients.  Since the closure devices are commercially available, they are routinely used off label.  Patients had little reason to enroll in a clinical trial.

Some journalists trumpeted the early use of closure devices and most academic medical centers started offering the service and some advertise the procedure on their websites.  Perhaps there is a lesson for all of us here.

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Comments (2)

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Larry Husten

March 23, 2012 at 3:05 pm

Actually, this is only one sad part of a much larger and much sadder story. The same company and technology was also involved in the infamous MIST trial, which tested PFO closure for migraines. The company ended up suing one of its own academic investigators. The whole sorry saga was covered extensively on TheHeart.Org and by many others, including a brutal takedown of the company by Ben Goldacre. The good news is that the company is now out of business. The bad news is that the underlying issues here have never been resolved. This could all happen again, and indeed is almost certainly happening right now.