Wider Use of Statins Should Have Been Rejeced

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. 

References:

1. 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
2. Hlatky MA (2008) Expanding the orbit of primary prevention – moving beyond JUPITER. New England Journal of Medicine 359 2280–2282
3. Rajpathak SN et al (2009) Statin therapy and risk of developing type 2 diabetes: a meta-analysis. Diabetes Care 32:1924-1929

Comments

[Dan]

Hi Justin,
I'd like some advice on convincing relatives to stop taking statins. I talk all I want about what I've read, but it doesn't matter.

They just listen to their doctor, a head of internal medicine at the hospital.

Bottom line is they have faith that because of his position, that he has the wiser words. What do you say to metacognitive issues with doctors, patients, and statins? I need to discredit this doctor, it's the only way!

[Justin Smith]

Hi Dan,
I'm sorry to say that I do not think there is much more you can do. I fully understand that it is frustrating, but all you can do is provide the facts and then respect each individual person's decision. The latest meta-analysis of statins shows that 99.4% of people who take them do not receive any benefit in primary prevention. And we have no-idea of the long-term effects of taking a statin for more than a few years. Unfortunately, the risks and benefits associated with statins have been grossly distorted by large pharmaceutical companies. All we can do is present the facts accurately and leave it up to individual people to decide how they would like to use the information. I'm sorry I can't be of more help on this aspect!

[Danielle]

So the assumption is that those with high cholesterol have a higher risk of some kind of heart problem...but is this LDL or HDL? And does it matter? I've recently read on a site linked to this one, that cholesterol isn't that big of a deal. If that's the case, then even those w/high cholesterol wouldn't need this medication, yes?

[Justin Smith]

Hi Danielle,
You are right. A person's cholesterol level has got very little to do with their risk for heart disease. Total cholesterol and LDL levels are quite meaningless in themselves. One thing that is important is the size of the LDL particle (not the number of them but the actual size of the particle), but this is usually not measured in a standard test. Cholesterol is just being used a convenient way of finding people to give medications to! However, statins do lots of things and not just lower cholesterol. Generally, there may be an argument for giving statins to very high risk people but even for these people the data is insufficient because all statin clinical trials have been too short in duration to assess the long-term effects.