Statins — when is a side effect of a drug not a side effect?

The BHF Medical Director, Professor Peter Weissberg, considers the findings of a major review of statins evidence and why the side effects of the drugs may not be as common as reported.

The review published in The Lancet today by a group of world-leading clinical scientists, including BHF Professors Sir Rory Collins and John Danesh, and the accompanying leading article written by the Editor, Richard Horton, focus on the vexed question of whether statins are as beneficial as guidelines suggest.

The ‘controversy’ hinges not on whether statins are capable of preventing heart attacks and strokes — just about everyone agrees that they are, but on the frequency with which they cause side effects and the extent to which those side effects might outweigh their benefits.

So, what is a side effect?

Professor Peter Weissberg, BHF Medical Director

If your doctor prescribes a drug for you and you develop an unpleasant symptom, say a headache, soon after taking the drug, you are quite likely to conclude that your headache is due to the drug (even though you from time to time experience headaches anyway), particularly if you have read in the patient information leaflet that the drug you are taking can sometimes cause headaches.

Whether you continue to take the drug or not will depend on how much you are prepared to put up with the headache to gain the benefit from the drug. If the drug is relieving distressing symptoms elsewhere in your body, you might decide to continue taking it anyway because you have judged the benefits outweigh the side effect. But if you are unable to judge whether the drug is helping you or not, as with a statin that does not relieve any symptoms, but does potentially prevent you from having a heart attack at some time in the future, you might decide that you don’t want to put up with the headache and stop the drug.

To help you and your doctor decide whether you should or should not take a drug, such as a statin, what you need is quantitative information on the likelihood of the drug benefiting you and the likelihood of the drug causing you harm, so that you can judge for yourself whether you would like to take the drug.

Doctors and patients need objective evidence

Because doctors and patients are all susceptible to biases and unfounded beliefs, both need objective, unbiased evidence on which to base their decision. Such evidence comes from randomised, placebo controlled trials in which some patients receive the active drug and others receive a placebo (dummy version which has no effect) and neither the patient nor the doctor knows who is receiving what until the end of the study period. All patients participating in such studies are forewarned of possible side effects.

Statins have been subjected to a large number of such studies and the results show conclusively that those patients taking the active drug have fewer heart attacks and strokes than those taking the placebo, which is the good news. They also show that somewhere between 10 and 20 per cent of patients will experience muscle pains and stop their treatment. But when the trial ends, and it is revealed which people took the active drug or the dummy version, it turns out that as many of them were taking the placebo as were taking the statin. In other words, although they clearly experienced a side effect which was bad enough for them to stop taking the tablets, it was not caused by the active ingredients in the statin.

But, the studies have clearly shown that when compared with people taking the placebo, people taking the statin were more likely to get a serious form of muscle problem called myopathy, but this occurred very rarely; they were more likely to develop type 2 diabetes and they were more likely to suffer a form of stroke caused by a bleed into the brain, although they had far fewer strokes caused by a blocked artery. Each of these is therefore a ‘true’ side effect of the drug, but each occurs rarely.

So why the controversy?

BHF Professor Sir Rory Collins who led the review published in The Lancet

This occurs because when doctors prescribe statins in routine clinical practice, many patients complain of experiencing a side effect. After all, we know from the randomised studies that this occurs in 10 to 20 per cent of patients even when they are taking a placebo. So the doctor’s ‘anecdotal’ experience leads them to believe that side effects are common ‘in the real world’. This is undoubtedly true, but the results of the controlled trials tell us that all but a few of those side effects are not actually due to the drug itself.

The articles in The Lancet today highlight the hard, objective findings of the major statin trials and conclude that the evidence for benefit is overwhelming. Furthermore the review quantifies the true harms that are due to taking statins. Doctors should use this information to help them and their patients decide whether or not it would be in the patient’s best interests to take a statin or not.

Who should be taking a statin?

If you have already had a heart attack or stroke, or know you are at high risk of either, then the evidence clearly shows that your outlook will be better on a statin. But if the statin doesn’t suit you, speak to your doctor who can change either the dose or brand of the statin to one better suited to you.

If you are healthy but want to know what your personal risk of a heart attack or stroke is, your doctor should easily be able to tell you and armed with the information in this review should be able to guide you as to whether it is in your best interest to take a statin or not.

Find out more about statins on the BHF website.