New Guidelines on Prescribing Statins

February 17, 2014

Note: This post is meant for educational purposes only. Please consult your doctor for decisions regarding medication.

 

The American Heart Association and the American College of Cardiology recently changed the guidelines for prescribing statins, drugs used to lower blood cholesterol levels. Statins have already seen their share of controversy over whether they are truly effective and if their risks are actually known. This new decision heightens the controversy because of skepticism over the motivations behind this change. Over 32 million  people are already on statins. Some cardiologists estimate that the new guidelines would double  the number of prescriptions. To put dollars  to it, in 2010, Liptor sales were in the range of $13.3 billion and Crestor was around $5.38 billion. In order to evaluate the ethical issues surrounding these new guidelines, we need to understand how statins work, because, as it turns out, the new guidelines change the criteria for prescribing statins to being a preventative measure rather than a response to a condition.

 

How Statins Work in the Body

Most people know that high cholesterol is not good because it is associated with heart disease, but they may not know why. Heart disease is a symptom of too much cholesterol in the blood; however, cholesterol, by itself, is not bad. Our bodies need cholesterol to sit on the surface of our cells to help build and maintain the cell membrane and to play a role in letting nutrients into the cell. Additionally, cholesterol plays a role in producing several important compounds in our bodies. Cholesterol, even the “bad cholesterol,” is actually good for us, up to a point. Too much cholesterol, on the other hand, can pose health problems.

Cholesterol is a chemical compound that is classified as a type of steroid. Think of steroids as chemical “signals.” When people report their cholesterol numbers, they will often refer to “good” cholesterol, or HDL, and “bad” cholesterol, or LDL. What they are really referring to are lipoproteins that transport cholesterol in the body. LDL stands for “low density lipoprotein.” Its main task is to carry cholesterol from the liver to the cells. HDL stands for “high density lipoprotein,” and it serves to transport cholesterol away from cells and back to the liver.

Statins reduce the amount of cholesterol produced in the liver, which will reduce the amount of cholesterol being transported to cells. Some people think statins lower the “bad” LDL levels. They do, but only indirectly, by slowing down the production of cholesterol in the liver, which causes a chain reaction that eventually leads to lower LDL levels. Cells only need so much cholesterol, so when there is excess cholesterol, more LDL is made and sent into the bloodstream transporting cholesterol to cells that do not need it. This causes cholesterol to build up, which becomes dangerous when it builds up in the arteries inhibiting blood flow.

For a more detailed description of statins, see “What are Statins? How Statins work and the side effects of statins “ and “What is cholesterol? What causes high cholesterol?“

 

New Guidelines

Statins are a particular class of drugs, some of which are stronger than others. Prior to the new guidelines, the rule was to “treat to target” meaning that if your LDL-C levels were above 70-100 mg/dL, then you were put on a statin (target HDL-C is above 30 mg/dL). Often patients were put on other drugs in addition to statins to lower their LDL-C levels. These statins are meant to be taken along with proper diet and exercise.

The new guidelines are no longer based solely on LDL-C levels, but are based on other risk factors for heart disease. Some of the reasoning behind changing from a “treat-to-target” to a more holistic approach includes:

  • The target LDL-C number of 70 mg/mL is not based on clinical data
  • Clinical data shows that cardiovascular disease was reduced by giving patients the maximum tolerated statin dosage
  • By only looking at an LDL-C target, patients may be put on too low of a dosage of statins, or put on LDL-lowering, non-statin drugs that have not been shown to decrease the risk of cardiovascular disease

The new guidelines provide a framework for placing patients on statins. They consider four statin benefit groups:

1)      People who have a history of cardiovascular disease

2)      People with LDL-C level at or above 190 mg/dL

3)      People 40-75 years old who have diabetes and LDL-C levels between 70-189 mg/dL

4)      People without clinical cardiovascular disease or diabetics who are 40-75 years of age with LDL-C levels between 70-189 mg/dL, but who also have an estimated 10-year cardiovascular disease risk of 7.5% or higher

I talked with Dr. Jay Hollman, a cardiologist in Baton Rouge. He agrees that new guidelines were needed because certain non-statin drugs which may lower cholesterol were not found to lower cardiovascular risk. Furthermore, he points out that “these guidelines do not recommend placing people with ‘normal LDL-C’ on drugs unless they have evidence of cardiovascular disease or have a high risk of cardiovascular events over the next 10 years. Diabetics are something of an exception since they have a higher risk and studies have shown that statins are of value in this group unless their LDL-C is unusually low.”

One feature of the new guidelines that has come under fire is the online calculator. The new guidelines put multiple pieces of information into a risk calculator that is meant to be used to aid doctors in assessing a patient”s risk of developing cardiovascular disease over a 10-year period. If the patient’s risk is 7.5% or higher, the new recommendations say the patient should be put on a moderate or high dosage statin. The American Heart Association and the American College of Cardiology recommend a higher dosage of statins than was previously thought, but they also recommend not combining statins with other cholesterol lowering drugs. The calculator, as well as the recommendations, is based on clinical trial data.

(For a more detailed discussion on some of the advantages of a holistic approach toward prescribing statins rather than solely by LDL numbers, see this article in Nature. Also see the original research article in Circulation.

 

Criticisms on the New Guidelines

Several medical health professionals have voiced concerns over the new guidelines. The major concern is that the new guidelines will result in overprescribing statins. Some speculate that these new guidelines are an effort to cater to the pharmaceutical companies that will financially benefit from increased statin sales. Others have expressed concerns over giving healthy people drugs with known side effects . Finally, some question the validity of the data that goes into the online calculator.

An article in The Lancet by Dr. Paul Ridker and Dr. Nancy Cook addresses concerns with an early version of the online risk calculator. Ridker and Cook looked at data from patients who have been involved in clinical studies for several decades to see if the calculator could accurately predict the patients”™ risks based on what actually ended up happening to them. Their data suggests that the risk calculator “over-predicted risk by 75 to 150 percent.” However, the risk calculator is only meant to be used as one of the considerations that go into whether a doctor prescribes a statin or not.

The calculator is not meant to take the place of the doctor-patient discussion on whether statins are a best course of action. Dr. Gregory Rutecki, a physician with the Cleveland Clinic, told me that the guidelines will “simplify the doctor-patient conversation.” The guidelines specify four categories of people who stand to benefit from a statin regimen. Additionally, the guidelines help physicians identify “high-intensity and moderate-intensity statin therapy for use in secondary and primary prevention” (Circulation, p. 11) Rather than aiming for a particular LDL number, the guidelines are a much more straightforward way to assess patient risk. Dr. Rutecki contends that while the new guidelines may risk over-predicting the number of people that should be on statins, it is still a work in progress. With time, doctors will be able to refine biomarkers and more accurately assess risk. The guidelines are based on clinical trial data, and with additional data, risk assessment can be refined.

(See Dr. Rutecki”™s editorial in Consultant, “Cholesterol Management 2013 and Beyond: Two Roads Diverge.”)

Statins have been a billion-dollar industry, which has caused many people to question the motivations behind changing the guidelines. However, while drug companies who make statins stand to benefit financially from these guidelines, all of the major statin drug patents have expired, except for Crestor, allowing for generic drug use. This would seem to mitigate some of the financial benefit that drug companies would receive from additional prescriptions. Furthermore, the new guidelines call for decreasing the use of additional drugs that have not been shown to reduce the incidence of cardiovascular disease.

 

Bioethics Issues

One key concern from a bioethics perspective is whether otherwise healthy people will be prescribed a drug that has known side effects. The new guidelines change when statins are prescribed. They go from being a reaction to a high LDL number or heart disease to a pre-emptive measure. This changes the discussion when it comes to risk and benefit analysis. Pharmaceuticals that are given to an otherwise healthy person should be held to a higher standard when it comes to side effects.

The Mayo Clinic website reports that some of the more serious side effects include liver damage, muscle pain (the incidence of which increases with higher dosage) which could lead to kidney damage, increased blood sugar, and there is inconclusive evidence for memory loss while on statins. I talked with Dr. Hollman and Dr. Rutecki about the incidence of side effects in practice. Dr. Hollman notes that these side effects are extremely rare. Dr. Rutecki points out that the idea that statins cause liver disease has been debunked in the last few years. He has found that rare side-effects, such as muscle damage, can be eliminated by putting the patient on a different statin or by decreasing the patient”™s dosage and that statins have not been found to cause permanent damage in the patient.

The doctors who drafted the new guidelines have responded to criticisms as well by pointing out that the new guidelines are based on extensive research and are meant to address the risk of stroke, as well as high cholesterol. According to The Wall Street Journal, “The researchers identified the 7.5% risk threshold as the point where the benefits of statin therapy to prevent first heart attacks or strokes clearly outweighed the risks, including muscle pain and a small risk of diabetes.”

A recent opinion editorial by Professor Jason Karlawish of Pennsylvania University points out the problem with relying solely on data as a diagnosis tool. While the online calculator appears to be objective, it is only as good as the data that goes into it. Karlawish questions whether the data accurately represents the population and whether the construction of the calculator, which is used to determine whether someone should go on a drug, has had appropriate review and oversight. His concerns echo other concerns with the online calculator and bring up an important issue of oversight when it comes to the diagnostic tools that are used in healthcare.

While relying on technology as a diagnosis tool brings up ethical questions, the Circulation paper addresses all of the concerns that have been voiced in the media, and does not indicate that the online calculator is meant to be the only tool physicians should use in assessing patient risk for heart disease. It clearly states “These guidelines are not a replacement for clinical judgment; they are meant to guide and inform decision-making” (Circulation, p. 18)

Overall, the new guidelines are based on updated clinical trial data that address several risk factors for cardiovascular disease. As with any financially lucrative pharmaceutical, people are reasonably wary of recommendations that stand to benefit pharmaceutical companies; however, one should not outright dismiss the guidelines out of paranoia over big pharma. Instead, it is important to consider whether the old guidelines needed updating based on new findings. Finally, there is no such thing as a “magic pill.” Statins stand to benefit many patients, but they are meant to be used along with lifestyle changes. When considering the ethics of pharmaceuticals, we need to be careful to consider the drug within the context where it is meant to be used.

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