Friday, December 18, 2009 at 2:16PM
This week, a Food and Drug Administration (FDA) advisory panel recommended that the use of statins should be expanded to include people who do not have high cholesterol levels. This would make an additional six million people eligible for taking the statin drug Crestor in the USA. It will then only be a mater of time until similar recommendations are followed in the UK and the rest of the world.
This all started with a clinical trial known as JUPITER. The results of this trial where published in the New England Journal of Medicine in November 2008 (1). These results have been grossly exaggerated and serious drug adverse effects have been played-down.
It was widely reported in the media that the statin used in this trial reduced the risk of cardiovascular events by 44 percent. However, this was a relative percentage reduction.
The reporting of relative percentages is a very common trick used by drug companies to exaggerate any slight benefits associated with their products. In reality, 2.8 percent of people in the placebo group suffered cardiovascular events compared with 1.6 percent in the statin group. So the risk for cardiovascular events was reduced by 1.2 percent, and not 44 percent!
Now, 1.2 (the actual risk reduction) is around 44 percent of 2.8 (the risk experienced by those in the placebo group), so thats where the widely reported 44 percent comes from. But patients should be told that this in reality equates to just 1.2 percent.
But it gets worse:
If we look at what has been referred to as ‘hard cardiac events’ (heart attack, stroke, or death from cardiovascular causes), 1.8 percent of the people in the placebo group suffered these events compared with 0.9 percent in the statin group (2). So, the risk for the most serious cardiovascular events was only reduced by 0.9 percent.
And even worse:
At the end of the day, the most important thing to look at is deaths from all causes. Since, there is not much point in taking an expensive medication if the risk for one disease is reduced at the cost of increasing the risk for another disease within the same time period. In the JUPITER trial, the statin reduced the overal risk of dying by about 0.5 percent.
Again, this 0.5 percent was quoted in the media as a 20 percent relative risk reduction, which is misleading for patients.
And then the adverse effects:
In the JUPITER trial, the statin actually caused more people to develop diabetes. The researchers dismissed this as a chance finding, but this increased risk was comparable to the benefits. The number of lives saved (from all causes) was around the same number of additional cases of diabetes.
It is often difficult for us to imagine risk as a percentage - if we imagine a theatre containing 1000 people who all take the statin for the next two years – around 5 people will have their life extended and around the same number will develop diabetes as a direct result of the drug.
The problem of course, is that an individual person has no idea if they will be one of the few people who have their life extended or one of the people who develop diabetes.
Other studies have also shown that statins increase the risk for diabetes. This was confirmed recently by a meta-analysis (3). In this analysis, the increased risk was reduced if the WOSCOPS study was included in the analysis, but the WOSCOPS study used non-standardised criteria for diabetes diagnosis.
There are also potential unknown longer-term adverse effects. JUPITER was very short in duration (just under two years). The presence of diabetes drastically increases the risk for cardiovascular disease but these increased risks would not be seen in just two years – it would take at least two decades for us to see the effects.
The wider use of Crestor, or any other statin, on the basis of the JUPITER trial, would, in the best case scenario, expose patients to as many risks as benefits at considerable financial cost.
- Ridker PM et al (2008) Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. New England Journal of Medicine 359 2195–2207
- Hlatky MA (2008) Expanding the orbit of primary prevention – moving beyond JUPITER. New England Journal of Medicine 359 2280–2282
- Rajpathak SN et al (2009) Statin therapy and risk of developing type 2 diabetes: a meta-analysis. Diabetes Care 32:1924-1929