Several weeks ago I wrote a piece that reported on a paper (Shalev et al., 2009) that indicated that those patients that adhered to their prescribed statins had a decreased mortality rate compared to those that did not adhere.
The problem with the statin study, as Dr. Eades points out, is the separation of those that self-adhered to taking the drug and those that didn’t adhere. Because maybe the type of people that don’t adhere to their prescription are fundamentally different that those that do adhere. One possibility is that those adhere to their medication care more about their health.
Dr Eades talks about a near 30 year old New England Journal of Medicine study and points out these interesting results of this pre-statin drug used to lower cholesterol:
Subjects were randomized into two groups - those in one group got the drug, those in the other got the placebo. After the subjects were on either the drug or the placebo for five years, researchers calculated the mortality from the number of deaths in each group. Turned out that the five-year mortality of those on clofibrate was 20.0 percent whereas the five-year mortality of those on the placebo was 20.9 percent, or essentially the same. Taking the drug was no different than taking the placebo, i.e., the drug was worthless. Had one of the researchers not looked a little closer, that would have been the end of the story.
When the data were looked at from the perspective of how many people actually took the drug as prescribed, the researcher discovered that those subjects who took at least 80 percent or more of their clofibrate had a five year mortality of only 15.0 percent, substantially less than the overall five-year mortality. Those who took their clofibrate sporadically had a five-year mortality of 24.6 percent, significantly higher than those who took it as directed, a piece of data that would seem to confirm the efficacy of clofibrate. Right? Not necessarily. Let’s look at compliance with the placebo.
Turns out that those subjects on the placebo who regularly took their placebo had a five-year mortality of 15.1 percent while those who took their placebo sporadically had a five-year mortality of 28.3 percent. What this study really showed was that there is something intrinsic to people who religiously take their medicine that makes them live longer.
You should read his complete piece, but I think you get the general story. The bottom line is it didn’t matter if you were taking the medication or the placebo you lived longer if you were the type of person that would adhere to taking your ‘medication’. And among those that regularly took their medication there were no difference between those that received the cholesterol lowering drug or the placebo.
Dr. Eades goes on to point out another paper published in Lancet that found very similar results (Granger et al., 2005). In this case they were looking at congestive heart failure comparing a drug and placebo.
Those taking the drug (Candesartan) showed no difference in mortality compared to those taking placebo. But when compliance was evaluated, those taking either the drug or the placebo as directed had much lower mortality than those taking either one sporadically.
Going back to the 2009 cholesterol lowering statin drug study the reported decrease in mortality is in the group that regularly took their medication compared to those that didn’t bother to take their medication regularly. And now you know from the 30 year old study this type of measurement (study) is not very valid.
Dr. Eades piece goes on to dive into further details such as all the actual randomized double blind clinical studies while reducing cardiovascular death in those with increased LDL levels, do not show any reduction in overall mortality (he argues there is an actual increase in cancer and other causes of death that balances out the gains in the cardiovascular system).
He concludes (but read the whole piece):
Don’t fall for the false promise of this or any other version of an observational study. These kinds of studies do not prove causality. Nor do they prove that a drug regimen works. The patients in this study who religiously took their statins had better all-cause mortality than those who didn’t. But, as we saw above, adherers always have better all-cause mortality than non-adherers. In this case, was it that the adherers lived longer or was it that statins conferred some sort of benefit. We can’t tell. But we do know that in the real studies, the randomized control trials, statins didn’t do squat, so my vote would be that what we’re seeing here is an adherer effect and not a statin effect.
I am not saying I agree with all the views and opinions of Dr. Eades, but I think his argument regarding the above discussion is valid.
(Dr. Eades also correctly points out how it is impossible (or nearly impossible) to run a correct randomized double blind studies with many lifestyle interventions - such as the exercise study I discussed yesterday - and hence you can not ‘prove’ anything with these type of interventions).