Monday, March 13, 2006

Homocysteine- three randomized trials suggest maybe everyone will not benefit from supplementation with b12 and folate

A pre-publication release from the NEJM on line gives us the results of 2 randomized trials (RCTs) which investigated the effects of treating patients with known cardio-vascular disease with folic acid and B12. These trials known as the HOPE 2 trial and the NOVIT trial join the previously published VISP trial.

Overall, there was no benefit in terms of the composite end point of recurrent myocardial infarction,stroke or sudden cardiac death. In HOPE 2, there was a statistically significant reduction in stroke among treated patients versus placebo. In all 3 trials the treatment did reduce the homocysteine levels. The concept of using composite end points is interesting and leaves me a bit puzzled. What is the rational of adding up cases of MI and strokes? Is not each outcome an important concern per se? How do authors decide to lump or split outcomes?

These trials do not provide evidence against the practice of attempting to lower elevated homocysteine levels in patients with CV disease as the trial treated all comers , not just those with elevated levels. What about patients with elevated levels and no history of CV disease?

I cannot leave this topic without noting a meta-analysis quoted by the editorialist in the same NEJM issue as the two articles quoted above. That article "determined" that a 25% reduction in the serum homocysteine levels was associated with an 11 % lower risk of ischemic heart disease. The fact that we now have 3 RCTs that contradict a Meta-analysis should no longer be noteworthy as we see that more than occasionally. My point is that to imply such precision exists in how much benefit will accrue from a given therapeutic manipulation based on a meta-analysis is not warranted and approaches the threshold for silliness. When authors do that it applies a coat of "apparent validity" paint to a structure held together by a complex collection of assumptions.

After I use up my current supply of b12 I guess there is no reason to buy any more.

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