Monday, June 19, 2006

A "simple" question

Ok, I just had my first patient call and ask to be taken off of Advair because of the recent press regarding the "risk" of death associated with long-acting beta-agonists. See the following editorial:

Martinez FD, NEJM December 22, 2005

and the recent meta-analysis:

Salpeter SR, Ann Int Med, June 20, 2006

Here's a figure from the Salpeter paper:



Our goal here is not to turn the blog into a journal club, but I think this has important implications on both practice and liability. Am I the only one who thinks that while the "relative" risk is increased, the "absolute" increased risk is amazingly small. I'm not sure that the increased "risk" outweighs the benefits of LABA's in patients with moderate or severe persistent asthma, or in patients with COPD who remain symptomatic despite anticholinergics.

So, I'm interested to hear how the pulmonary community is approaching these data...

5 comments - CLICK HERE to read & add your own!:

james gaulte said...

I agree with editorial in the same issue of Chest that published the SMART trial results.(O'Byrne and Adelroth)-Chest:2006;129:3-5-Admitedly it was published before the Salpeter paper, but they did not recommend stopping salmeterol.
The SMART trial was one of worst trials ever in many regards and I hope it will not cause widespread d/c ing salbuterol containing drugs.I talked about some of SMART's problems in recent blog. (Retired doc's Thoughts).I am still pondering the Salpeter article.

Baleeiro said...

Jeff, I think that is a great question. I have had several patients asking me about Advair, I have seen the issue discussed on TV and on NPR...
To me there are several problems to how this was handled.
One is that, indeed LABA alone should not be the preferential maintenance therapy for asthma. The problem with increased mortality happened mostly in inner city kids with poor access to health care who felt better but had worsening inflammation and when they got help it was too late. That should not translate into LABAs, even coupled with an ICS are always bad.
I also get a lot of questions from old smokers with no asthma who might be on Spiriva and Foradil to try and improve their dyspnea and I don't think the problems with asthma and LABAs apply to them: different diseases, different inflammatory cells, an most of my COPD patients are not inner city youths.

Mike L said...

I think carlos' point is the KEY to this argument. These studies that are listed are mostly ones performed with drugs in the ABSENCE of inhaled corticosteroids.
In the studies that include corticosteroids there is no data showing an increased risk of exacerbation or death from LABA.
Also, as CEOB mentions, these studies are performed in asthmatics.
My practice is to begin LABA in asthmatic individuals only when they are not controlled with inhaled CS. COPD is a different disease, and I rarely use LABA without ICS in those patients as well.
As an aside, GSK people should use this as a marketing ploy so that people do not use LABA's without a steroid/

DrJon said...

The down and dirty way we learned looked at the CI. In all of those studies, the CI at the 95% contained 1.0, which indicates no increased risk. Can that "rule" be applied here as well? Also, the CI for the Serevent and Foradil 040 studies are all over the place. If there is an increased risk, it is very very small.
Am I off base in my approach to this?

Jeff H said...

I agree. This meta-analysis seems a to be like statistical alchemy. If we combine several studies that failed to show any statistically significant differences, then we magically produce a statistically significant result.

Even if there is a "statistically significant" increased risk, I agree that it is, indeed, very small.

Of course, lawyers don't see it this way. Just google "Advair" and see what pops up in the top 10 links...