Friday, April 22, 2011

Meta-analysis fails to show all-cause mortality benefits to statins in primary prevention

A 2010 meta-analysis by Dr. KK Ray et al ( see here for full text) in the Archives of Internal Medicine stirred a bit of interest and commentary as it failed to show an all-cause mortality benefit from statin use in the setting of primary prevention in patients with elevated risk factors for coronary artery disease.

A few context setting comments are in order. First, it is well established that statins are clearly beneficial in secondary prevention of coronary disease. In patients with proven coronary artery disease few would disagree with statin use.Its efficacy and safety have been demonstrated in several of the well known so-called landmark statin trials.

Second, the argument is strong for the conclusion that statin use in primary prevention results in a decrease in cardiovascular (CV) deaths. The authors of the Archives article make their position clear in that regard when they say in their comments sections "the benefits of statins in CV deaths are unequivocal based on primary prevention data from the CTT meta-analysis." The Cholesterol Treatment Trialist Collaboration or CTT was published in Lancet in 2005 ( see here ) .

So, the issue that Ray and his fellow authors addressed was not do statins reduce CV mortality in primary prevention but do statins reduce all cause mortality and their data analysis lead to the conclusion it does not.

Ray analyzed data from 11 randomized clinical trials of patients with what they considered to be high risk for coronary artery disease ( 244,000 patient years). Big numbers for patient years tends to give credence to findings but the key thing here is that in these trials the follow-up period was only 4-5 years as is typical of clinical trials. In patients with increased CV risk -as opposed to patients with proven CAD-the ratio of CV deaths to total deaths is relatively low particularly in a 4-5 year time frame. So that it is not surprising that all cause mortality may not be decreased, which is what Ray demonstrated.

Both the editorialist in the Archives and a subsequent commentator in a Update section in the April 5, 2011
Annals of Internal Medicine seem to conflate failure to show decrease in all cause mortality in a short observation period with overall lack of benefit. Ray and co-authors do not deny benefits in terms of decrease in C-V mortality.
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