COMMENTARY

Statin Expansion: Hold the Rx

Rita F. Redberg, MD

Disclosures

March 26, 2014

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Why We Wrote the Op-Ed

Hello. I am Rita Redberg, Director of Women's Cardiovascular Services at the University of California San Francisco Medical Center, and today I would like to address the recent cholesterol guidelines.

I wrote an op-ed in the New York Times titled "Don't Give More Patients Statins"[1] recently. I have been interested in primary prevention of heart disease and the best way for cardiologists to advise our patients on how to prevent heart disease for many years, and have written a few editorials over the years on the subject of primary prevention and the role of statins. I keep up very closely with the literature on primary prevention and statins and have also published some articles on that topic in the journal that I edit, JAMA Internal Medicine.

I had seen a copy of the new cholesterol guidelines the weekend before they were coming out, and they were anxiously awaited by me, as well as all of you, for many years. I had certainly thought about them, and was contacted by a colleague and one of the authors of other work on primary prevention and statins at Harvard: John Abramson, who felt the same way that I did about the strengths and weaknesses of the new guidelines. Together, we decided to write the op-ed for the New York Times because we thought that there were very important messages.

Primary prevention of heart disease is an incredibly important area, and it is important that we concentrate on the right things. Although there were a lot of good things in the new guidelines, overall we thought that they were likely to lead to more people taking statins, where there was no evidence of benefit for statins. That is what led us to write that op-ed.

We thought that this was very important information, and our first responsibility is to our patients, to give them the right messages. There were a lot of strengths in the new guidelines -- in particular, the emphasis on risk and tailoring our prevention treatments to the level of risk in patients, and so the focus on risk was very important.

However, other things in the guidelines were not based on evidence. For example, I could find no evidence for the change in the risk threshold to 7.5%. I still find no evidence in the guidelines or anywhere else for dropping the risk level to 7.5% and recommending statins on that basis.

Questionable Risk Calculation

The new risk calculator has also been covered on Medscape as well as other places, such as Paul Ridker's Lancet article.[2] Clearly, the risk calculator seemed to have problems with validation.

I happened to be at a medical meeting the day after the guidelines came out, and a colleague sitting next to me showed me that he had done his own risk calculation using the new risk calculator. He was now at 17%, and he told me that the day before on the old risk calculator, he was at 7%. He was about 70 years old but otherwise totally healthy, with absolutely no risk factors, worked out every day, and had a low cholesterol level.

Besides the fact that there hadn't been validation and there were problems when validations were done in large populations, as Paul showed, I couldn't understand why a risk calculator would suggest that a healthy 70-year-old man with no risk factors would be a good candidate for statins. So, I think that the next set of guidelines will address these issues and focus more on lifestyle.

The other issue, and the problem I have, is that the guidelines in general focused a lot on statins and on cholesterol levels. Curiously, however, the guidelines said that you didn't need to check the low-density lipoprotein cholesterol (LDL-C) -- which I think people found confusing, because all of our previous guidelines had focused on LDL-C. I am fine with not focusing on LDL-C, but the idea of having said that for 20 years and now saying, well, actually, there wasn't any evidence was confusing to a lot of patients and to many of our colleagues.

Those were some of the issues, and we wanted to turn the conversation on primary prevention to a focus on lifestyle, because that is where we get the most bang for our buck. We have so much room to move in terms of improving the overall American diet and lifestyle with regard to exercise and eating a heart-healthy diet. We have great data to show that the Mediterranean diet reduces heart disease risk factors.[3]

We felt that the focus of guidelines on primary prevention has to be on lifestyle changes, and that the whole conversation about cholesterol levels and telling patients that their heart disease risk is so closely tied to their cholesterol levels is not based on evidence and does not do a service to our patients. Overall risk is a much bigger picture, and cholesterol is just one small part of that. The other issue is that the primary prevention data are very weak in terms of the risk and benefits for statins in primary prevention.

Statins: Not Entirely Benign

The Cochrane review[4] published by Kausik Ray and colleagues in the Archives of Internal Medicine a few years ago showed little or no mortality benefit for statins in primary prevention. We have underestimated the risks, which are, in the more recent data, estimated to be about 20% of patients at risk for muscle aches and pains or at risk for diabetes.[5] The US Food and Drug Administration (FDA) has issued a warning about memory loss and statins. So, we need to be erring more on a patient-centered approach to primary prevention -- where we are really talking about your chance of getting a benefit from taking these drugs for many, many years is, at best, prevention of 1-2 heart attacks in 100 people who take the drugs for 5 years. In contrast, it is more like 20 out of 100 people who will have some kind of side effect that will even interfere with the quality of their everyday life.

The reaction from colleagues and patients has been very mixed. There has been some confusion over the change in the risk calculator, the change in the recommendations, and the going away from LDL-C levels. People have been positive about looking at level of risk and trying to make simpler recommendations about what to do if you are going to move to treatment.

It is certainly true that some statins are generic. Although the recommendations in the guidelines were pretty specific about what statins were considered to be aggressive treatment and the recommendation was that if you were at the threshold level of risk, you should be treated as aggressively as possible, of the statins that were listed, one was generic and one was still on patent. The conflict of interest is a separate issue and is very important irrespective of what other statins are generic.

It is important for cardiology and medicine as professions that our guidelines and our processes are seen as free of conflict. Many questions have already been aired, and the Chair had stepped down from 9 different speaker's bureaus, according to an earlier article in the New York Times,[6] in order to chair the guidelines, and the Vice Chair, maintaining a lot of research support from pharmaceutical companies, including those making statins. Whether that means that they were unbiased or not is not necessarily the point, but it is the appearance of conflict of interest that is important, and statins being generic doesn't change that conflict of interest.

The American College of Cardiology and the American Heart Association (AHA) have now issued their own guidelines on ethics. They went into effect during development of the cholesterol guidelines, which were very long in coming. I am sure we will be very thoughtful about this, because we are all concerned about the profession and our perception in the public, and conflict of interest is something that we don't want to stain and get in the way of our relationship and our ability to do great things for our patients.

Statins for Secondary, not Primary, Prevention

In my practice, I believe that the evidence supports the use of statins for secondary prevention, and I tend to follow those guidelines. For primary prevention, I don't think that the data show that the benefits outweigh the risks.

I believe for primary prevention, we are talking about healthy people. Healthy people are those who feel well even if they have risk factors. Many people have risk factors for heart disease, but when I read the data, I think the best way to prevent heart disease in healthy people is to help them develop a healthy lifestyle, including a Mediterranean-style diet and regular exercise. I am very aggressive at every visit in reminding people of the importance of exercise. I think it is the best medicine in terms of reducing heart disease risk, prolonging life, and improving quality of life -- which is a winning combination -- along with not smoking.

In summary, the strong point of these guidelines is the focus on risk. We want to remember that it should be a patient-centered discussion with a full disclosure of the risks and benefits of lifestyle changes, as well as the benefits of a statin in addition for primary prevention. For secondary prevention, I support the current guidelines, and I look forward to the next version of the cholesterol guidelines because I think that they will address some of the issues and concerns that were raised by this set of guidelines. Thank you.

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