Celebrating a Biomedical Research Success Story: The Statin Case Gets Stronger

Two cases about the use of medications called statins recently caught our attention. The first is a young man in his 20s who had just been told that a blood test showed he has an elevated cholesterol level. His doctor told him to decrease his intake of fatty foods and exercise more to try and reduce that level. The second is an elderly man in his 90s who has been taking a statin medication for years but does not recall ever having been told his cholesterol level is high and has never had a heart attack or stroke. Should the young man be put on a statin? Should the elderly man stop taking his statin medication?

It is rare that we term a class of medications “miracle drugs,” but statins may be close to fitting that description. Statin medications were discovered in the 1970s by  Dr. Akira Endo, a Japanese biochemist who also worked for a time at the Albert Einstein College of Medicine in the Bronx, NY. Endo showed that a class of chemicals that inhibit an enzyme called HMG-CoA reductase that is essential for cholesterol synthesis lowered cholesterol levels in laboratory animals. In 1987, the first statin medication, lovastatin, was approved by the U.S. Food and Drug Administration (FDA) under the brand name Mevacor. Since then, six more statins have been approved by the FDA. Today, about  45 million U.S. Americans take statins.

Statin Have Many Actions Besides Lowering Cholesterol

The reason to lower blood levels of cholesterol—and in particular the type called “bad cholesterol” or low-density lipoprotein (LDL) cholesterol—is clear: high LDL cholesterol levels are associated with an  increased risk for cardiovascular disease, heart attacks, and stroke. Statins substantially reduce LDL cholesterol levels and some also reduce the levels of another circulating type of fat, triglycerides. For people with high LDL levels or who are at high risk for or have a history of cardiovascular disease, taking a statin can have a major role in  lowering the risk for cardiovascular disease and stroke. Beyond that, there are intriguing indications that  statins have additional benefits. Not only do they inhibit HMG-CoA reductase, but they also stabilize atherosclerotic plaques, preventing them from breaking apart and causing further damage to small heart vessels, and they prevent aggregation of cells involved in blood coagulation, thus also decreasing the risk for clogged arteries that cause heart attacks and stroke. They can  reduce the risk of blood clots forming in the lungs and other organs. Furthermore, statins have  anti-inflammatory and antioxidant actions that are independent of their cholesterol-lowering effects. Thus, in addition to reducing the risk for cardiovascular disease and stroke, statins could potentially prove useful for diseases that involve excessive activation of the immune system, like  rheumatoid arthritis and an  eye condition called uveitis. They may also  reduce the risk for Alzheimer’s disease.

Statin Benefits Usually Outweigh Risks

No effective medication is  devoid of adverse side effects. The most common adverse side effect of statins is muscle pain, which occurs in about  five percent of people who take them. Rarely, they can cause a serious form of muscle damage, called rhabdomyolysis, which occurs in  a few people per million who take statins. There are also rare cases of liver damage among people who take statins, and they can increase blood sugar (glucose) levels in some people. These unusual adverse side effects from statins can be monitored with blood tests. Overall, for people at risk for or with a history of heart disease or people with elevated LDL cholesterol levels, the  benefits of statins outweigh the risks.  That has not stopped  misinformation about statins to flourish on the internet and social media. False claims include that high levels of cholesterol are not harmful, that dietary changes and more exercise alone are all that is needed to lower cholesterol levels for most people, and that statins are more harmful than studies have proven they are.  Many people who should be taking statins decline them because of fear of adverse side effects even though studies show that most people tolerate them very well.

Studies Continue to Demonstrate Statin Benefits

Two recent studies add to the benefit side of the equation for statins.  In a study published last May, a group of investigators from England and Australia showed that statin use across all categories of sex, age, LDL-cholesterol levels, and cardiovascular disease history or risk increased lifespan and improved quality of life. The study took into account the chance for adverse side effects in reaching that conclusion. It also showed that the use of statins was cost effective and that stopping statins reduced benefits and was not cost effective. The authors of the study concluded that “lifetime statin therapy is highly effective across all adults 40-70 years old, suggesting that both widening of statin eligibility and improvements in statin uptake among eligible people need to be pursued.”

The second study, also published last May, found that statins even reduced the risk for cardiovascular disease in people aged 75 years and older without increasing the risk for adverse side effects.

One potentially important challenge to getting more people who could benefit from taking a statin medication to be prescribed one is new guidelines for determining who is at risk for cardiovascular disease. The American Heart Association has proposed a new method for calculating cardiovascular risk that, according to a study published last September, will reduce the number of people eligible to receive statins. The study authors estimate that this will result in a substantial increase in heart attacks and stroke. While it is unclear to what extent these new guidelines will be widely adapted, they could represent a setback in ensuring that all people who might benefit from a statin receive them. 

Like any medicine, the decision to take a statin is one that requires careful consideration of risks and benefits. If the decision is made to start a statin, it is important to monitor the impact on blood cholesterol and triglyceride levels to make sure they are effective and to monitor for emerging adverse side effects. Clearly, however, most people who are at risk for or have a history of heart disease or who have elevated LDL cholesterol levels will benefit from taking them. It may be that people with other conditions also benefit from statins.

So, what should we tell our young man with high cholesterol and our elderly man who is on a statin but does not have a history of heart disease or high cholesterol to do? In the former case, while it is appropriate to recommend a change in diet and increase in exercise as first steps, there is a reasonable possibility that neither of these will result in a lower cholesterol level. If that is the case, he and his doctor should definitely consider starting him on a statin to lower his risk for cardiovascular disease and stroke. In the latter case, the elderly man has been taking a statin for many years without experiencing any adverse side effects or complications. He does have a history of high blood pressure (hypertension), which puts him at increased risk for a heart attack. It is likely that he and his doctor will decide that continuing the statin is a reasonable idea.

We often think of antibiotics as miracle drugs, and indeed they fit that description. Some may think that the new crop of anti-obesity drugs, the GLP-1 agonists, are also miracle drugs and that may well prove to be the case. But we shouldn’t forget that statins have been lowering the risk of cardiovascular disease and stroke for almost four decades and may also be lowering the risk for a host of other diseases. They have proven incredibly effective and safe. It is important to acknowledge the major successes that biomedical research has accomplished and to advertise those successes so that the maximum number of people can benefit from them.