Saturday, April 25, 2009

The tale of an Afib Device, Novelty and the FDA

Here is the link to the story:

Atritech (and not Artritech as mentioned in the Med Page article, as of this blog's publication time) is the manufacturer of the "Watchman" device, dubbed to be a "novel AF" device that the FDA has marginally approved as comparable to Warfarin.

The novelty:

The novelty part seems to be partly in the parachute shape and maybe in its implantation and somewhat in it's function? The article is quick to endorse the "novelty", yet lends no explanations to where the roots of this novelty lie.

The device:

Here is some information about the device:

1. The device is approved for "warfarin-eligible" patients with nonvalvular atrial fibrillation. (We will discuss what all this song and dance means shortly)

2. In terms of size, it appears that the device is about an inch in maximum diameter.

3. Placement: Left atrial appendage.

The idea behind the placement apparently is to block off the left atrial appendage, because it is assumed that the left atrial appendage is the major source of blood clots in patients with Atrial Fibrillation.

For evidence, look up this review of the Left Atrial Appendage Occlusion Study (LAAOS). (It's free by the way):

"Warfarin-enabled patients with nonvaluvular atrial fibrillation"

Based on their relationship to other valvular diseases, such as mitral stenosis, there are two types of atrial fibrillation: valvular (in the presence of valvular disease such as mitral stenosis) and nonvalvular atrial fibrillation.

For a good reference and review:

Because valvular diseases are better controlled in developed nations such as the US, about 70% of all Atrial Fibrillation is nonvalvular. And, because the good news is that people now tend to live longer, the bad news is that we see more people suffer from conditions such as Atrial Fibrillation, as people live longer.

There is a need to make sure that we treat people with atrial fibrillation. Warfarin is the most common medication used as a blood thinner for patients prone to thromboembolisms (blood clots, but we all love fancy names, don't we?). As with most medication, not everyone is eligible to take Warfarin, and even those who are on Warfarin need to take it on a regular basis.

Are there issues with warfarin?

It is somewhat stupid to state that there is necessarily a problem with warfarin, as much as with all forms of medication (or devices for that matter). The central focus of the issue seems to be that since people will be taking warfarin and since you can't risk slow releases or anything of that sort (too much blood thinner ain't good for you either), people will have to take warfarin on a regular basis for the rest of their lives. Naturally, this is a problem. This is where Watchman is supposed to come in.

What can Watchman do and why wasn't there a 12-0 approval?

There are a few things to think about:

1. The FDA may have finally been acting cautiously about approvals, or maybe the committee was doing the right thing after all...

2. For one, it is "assumed" that most of nonvalvular atrial fibrillation can be controlled by occluding (shutting off) the left atrial appendage. Since there are assumptions and belief systems are involved, there is no certainty that this device can replace warfarin.

3. Looking at the data submitted to the committee, we can note that there were 14 ischemic strokes (approximately 3%) compared to the 2% of ischemic strokes in Warfarin patients. There is no clear winner here, so the committee decided that the device was at best comparable to warfarin and is not better than warfarin.

4. Physician Training - seems to be a somewhat steep necessity. Apparently higher rates of pericardial effusion were seen in the device. Pericardial effusion is termed the high accumulation of fluids outside the heart in the pericardial region. The heart likes to be efficient about space use, and excessive fluid can cause increases in pressure, leading to a stressed heart. A small note - the article doesn't hint at exactly how many incidents were reported, something worth digging up (see conclusion below).

5. Words of Wisdom: There is one really scary thing - personally for me. That is, any device compared to "drug eluting stents". (If you want to know why, read the blog's archives).

Here is a quote and a repeat from Dr. William Maisel MD, stolen verbatim from the Medpage Today article:

"He said the Watchman has some of the same issues that the drug-eluting stent advisory panel -- which he chaired -- grappled with: a potentially huge patient population, trials with low rates of very serious events, and a lack of postmarketing data.

"I think the lessons from that are that it may sound like a great idea to roll it out quickly, but I hope the sponsor will be careful about where the device goes," Dr. Maisel said. "

The Conclusion:

I am still not clear on the presence of novelty in this device, but it may follow from a device that seems to have the potential to fit well with a large patient population well in need of relief.

The numbers reported so far don't look bad either: a 32% reduction of total risk in terms of stroke, embolic events and death related to cardiovascular events. In terms of mortality alone, there is a total reduction of 39%. All this looks very good.

However, I would agree with the committee. The approval is a boon for the company. They don't have to go back to the drawing board and get more data. Now, they can do a few things:

1. Train surgeons, so that the outcome issues such as pericardial effusion can be avoided. There may be opportunities here for the company to offer a next generation device that either reduces the possibilities for effusion, or helps easy implantation.

2. Collect long post-marketing data and report adverse events promptly to the FDA, unlike other companies that tend to wait for about six to n months.

3. Try to understand where the ischemic strokes are coming from. It seems like something to investigate and contain.

Since PLAATO, a device made by Appriva Medical, Inc. is veritably the first-in-class device and WATCHMAN is the second, if you are a competitor or a potential one, there are two things to note - you could use some time waiting for more data (or planning in your budget to generate more data) and also watch for lessons to learn, before jumping and starting the umpteenth stent, I mean appendage occluding device company....

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