This article was first published inÌý
For anyone looking to lower their risk of heart disease, there are five main modifiable risk factors. If you exercise regularly, stop smoking, control your blood pressure, treat diabetes and lower your cholesterol, you can drastically reduce your risk of having a heart attack. But while there is little debate around the first four risk factors, cholesterol and the medications used to treat it remain perpetually controversial.
Statins have a profound effect on cholesterol levels and have been subjected to more than 20 randomized trials by multiple research groups over several decades. Meta-analyses show that lowering cholesterol reduces the risk of cardiovascular events in patients with known cardiovascular disease (what we call secondary prevention) and to a lesser degree for people without cardiovascular disease (primary prevention).
Yet despite statins’ proven track record, numerous testimonials of horrific side effects scare patients off, often with unfortunate consequences. A DanishÌýstudyÌýfound that every time a news story cast statins in a negative light, there was a surge in the number of people who stopped their medications, followed by a spike in heart attacks and cardiovascular deaths. Statins have a terrible reputation that is strangely not shared by other cholesterol medications, even though some, like PCSK9 inhibitors, are more expensive and rather inconveniently require patients to inject themselves every two weeks.
Part of the problem with statins is the fear of side effects. Statins can damage liver cells and cause blood levels of liver enzymes to rise. Another problem is that statins can cause a myopathy, that is, pain and inflammation in the muscles, and raise blood levels of a muscle enzyme called creatinine kinase (CK). If CK levels rise high enough, they can in turn damage the kidney in a condition called rhabdomyolysis.
But, the incidence of both these side effects is low. InÌý, statins are responsible for about four cases of liver injury per thousand people. Incidence of muscle injury is generally under one percent, and not different from placebo.
The problem is that far more than one percent of people complain of muscle pain when starting statins, and despite their CK levels being normal, they continue to suffer with muscle side effects associated with the medication. The cause of these persistent symptoms is unknown.
One potential explanation was recently put forth in a study presented at the American Heart Association and published in theÌý. Researchers in Britain conducted an N-of-1 trial where patients who had previously tried and stopped statins due to side effects were alternately given atorvastatin, placebo tablets or nothing in one-month intervals for one year. Therefore, each patient served as their own control group.
The results showed that patient-reported pain scores were the same for both the statin and placebo months and significantly higher than pain scores in months when patients got nothing. In short, the simple act of taking a tablet made patients feel worse. This phenomenon has a name. It is called the nocebo effect.
This negative placebo effect is actually common, and researchers have found similar phenomena when analyzing data from theÌý. There too, there was no difference in side effects between statin and placebo when patients were unaware which medication they were taking.ÌýOnly after the trial, when patients knew whether they were taking a statin or not, was there a difference in muscle complaints.
The authors of the NEJM paper estimated that 90 percent of statin symptoms were reproduced by placebo. In school, a teacher once told our class that the anxiety before an exam was usually worse than the exam itself. When it comes to statins, for many patients, the fear of side effects seem to be worse than the side effects themselves.
