A reader asked me to dive into the current medical controversy over the use of statins — a wide-ranging topic that allows me to opine on a few related issues so, of course, I’m up for it! Briefly stated, statins are medications that are prescribed to lower cholesterol and are recommended by many physicians as a way to reduce cardiovascular disease. There are many statins on the market — Lipitor, Crestor, and Zocor, among others — and they have been shown to drastically lower cholesterol levels and reduce the risk of heart attacks in certain patients. So where is the controversy? Let me go back a bit…
My family and I lived in New Zealand for about 16 months, and one of our major reasons for pursuing this experience was to give us all the opportunity to view the world from a different vantage point, one that was not necessarily American. I knew that their medical system, a government-funded universal healthcare system, would be fundamentally different from ours in the US, but I didn’t expect there to be much difference in the actual practice of medicine. What I found was that most NZ medical protocols were similar to my familiar American ones, but there were, at times, some significant differences. Seeing these differences opened my eyes to the possibility of looking at medical data, among other things, from different perspectives.
On a rainy winter morning in late June of 2001, my registrar — what we in the US call residents — presented a patient to me that he had admitted the night before with a severe asthma attack. After I examined him, it was clear that the patient was seriously ill from his asthma and was headed for intubation and mechanical ventilation. I made some adjustments to the medications the registrar had started, primarily increasing the intravenous dosing of the steroid Solumedrol to 80 mg. every eight hours, standard protocol in the US. We moved on to the next patient, and about 20 minutes later, the hospital pharmacy called me asking what dose of Solumedrol I had meant to order, since 80mg. every eight hours was clearly a mistake. No, I reassured him, that is what I wanted. I didn’t think much about it, and I continued to move on with my day. At lunch, one of my new colleagues, a superb pulmonologist, sat down at my table and asked me about my steroid dosing. I didn’t know him well at that point, but his reputation was excellent, and after working with him, I found him to be just that, one of the brightest and most clinically astute physicians with whom I have ever worked. Paul questioned why I had ordered such an unusually large dose of steroids for this patient, as he would have ordered 40 mg. once a day, as my registrar had done. I responded that this was the standard dose of steroid that we used in the US for this severity of asthma. We agreed to bring each other some data and medical journal articles to support our different positions. Always up for a challenge, I finished lunch quickly and went to my computer to consult my go-to reference source, UptoDate.com. I printed out the recommendations for treatment of acute asthma exacerbations (attacks) as well as the reference article. The recommendations agreed with my dosing, but I noted that the supporting article, from a major medical research hospital, was about ten years old. (Unfortunately, UptoDate.com’s current bibliography no longer includes this article so I can’t reference it here for you.) After I finished my clinic, I went to Paul’s office and confidently presented my UptoDate information. He, of course, had seen all this data in the past and said that in New Zealand, and the British Commonwealth in general, this was not the accepted course of treatment. I then showed him the reference article and he agreed that this was, indeed, the study that is used as the “best available” data for the treatment of asthma, but his Commonwealth-based interpretation of this article was very different from that of US-based physicians. He believed that the article I showed him actually supported his lower dose. So here’s the thing — we have a very well done, and well-accepted, medical study that doctors in the US interpreted one way—high dose steroids—but doctors in the UK interpreted in exactly the opposite way—low dose steroids. WOW! We eventually respectfully agreed to disagree on this issue, but I tell you this story today to illustrate the point that the same data can be interpreted in different ways and that the practice of medicine, while based on science, is still very much also an art based on experience and inferential reasoning And that brings us back to the question, what to do about statins?
Statin drugs are the most effective medications we have to reduce serum cholesterol. We know that people with lower cholesterol levels have a lower risk of developing atherosclerotic disease in their hearts (heart attacks) and in their brains (strokes.) We also know, and this is not disputed, that people who have already had a heart attack have fewer future heart attacks when they are on a statin medication. But the majority of people who are taking statins are not people who have experienced prior heart attacks or strokes. They are people whose lab work shows either a high total cholesterol or a high LDL level. The data for these patients, especially the elderly, is less convincing, and this is where the difference in the New Zealand vs.US interpretations of the same study strikes a chord with me. Here is a very good study from 2013 published in the Journal of the American College of Cardiology. This was a meta-analysis, which means it compiles many study results into one, and it looks at people over 65 years old who do not have a history of heart disease or strokes. It delineates a very impressive and statistically significant 38 % reduction in heart attacks and a 23% reduction in strokes in patients taking statins. But since the actual risk of having a heart attack or stroke is not nearly as high as most people think it is, the actual statistical benefit derived from statin use is that only one or two people out of a hundred would be spared a heart attack, and only one person in 150 would be spared a stroke. Now if statins were a totally benign medication, like a multivitamin, without any significant side effects, those numbers, while small, would make taking it worthwhile. But statins can, and often do, have significant side effects including liver problems in every age group and muscle weakness, especially in the elderly. Additionally, statins increase the risk of diabetes and are probably even the actual cause for 1% of the people who develop diabetes. Just like the steroid dose issue in New Zealand, the same landmark article can be read in totally different ways depending on the physician’s point of view.
One method of evaluation of medication efficacy directly asks the pertinent question: what is the percentage of patients who are actually helped by using a medication versus the percentage of patients who are harmed by its side effects? Another method of evaluation looks at the actual of number of people who are helped by the medication versus the number that will have significant side effects. This very important consideration when prescribing a medication or devising a treatment plan is known as the risk benefit ratio. How much risk (side effects) is acceptable for the benefit (in this case, the reduction of heart disease and incidence of stroke)? While the percentage of people who will have side effects from a medication is typically well known, the actual benefit is often less clear. If a certain medication reduced the risk of heart attacks by 50%, this would be a very impressive statistic, but only if the risk of having a heart attack was high. If the risk of having a heart attack in a high-risk group of patients was factored at fifty heart attacks for every hundred patients, then this medication would prevent twenty-five patients out of every hundred from having heart attacks. This is an impressive number, and would almost for sure be a medication that these high-risk patients would be advised to take. But let’s say the risk for a heart attack in a certain group was only two in a thousand; then there would be only one patient in a thousand who would be prevented from having a heart attack by taking this medication, and to justify its use, the side effect profile of the medication would need to be very low. Historically, physicians have used the Framingham Study as their guide to risk for development of disease. The Framingham Study was a groundbreaking study that started in 1948 and followed over 5,000 people from Framingham, Massachusetts, for the development of cardiovascular disease. It is an ongoing study and it is now following third-generation Framinghamtons. The Framingham Study is where the term “risk factors” originated. There are a few known problems with the study but, overall, it was very well designed and implemented, and it is well-respected and often quoted. But there was a study published in the Annals of Internal Medicine in February of 2015 (see here ) that suggests that the Framingham Study over-estimates the risk, sometimes significantly, of cardiovascular events. This is important because If one over- estimates the risk of heart disease, then one will over-estimate the benefit of a medication that prevents heart disease. One focus of this Annals study was the concern that physicians are over-prescribing statins based on this corresponding over-estimation of cardiovascular risk. As I have stated many times before, medicine is continuously evolving, a constantly shifting target, and we sometimes don’t get things right because new data often supplants old data. We do our best with the best data available at the time we are making treatment recommendations.
Statins have made a lot of money for the pharmaceutical companies. 25% of all Americans over the age of 45 have been prescribed statin medications, and they are the most widely prescribed medications in the developed world. It would be a fundamental change in the way preventive medicine is practiced if statins no longer were considered essential for so many people. (It would also be a huge hit to Big Pharma profits.) So both the risk-benefit analysis and the accompanying controversy will continue until we have more definitive data.
So herewith are my most basic medical recommendations regarding statins:
- If you have cardiovascular disease as represented by having experienced a stroke, heart attack, angina or peripheral vascular disease, you should be on a statin, barring other contraindications.
- If you are elderly or have a relatively limited life expectancy for other reasons, you should probably not be on a statin.
- If your risk factor for having a heart attack or stroke is higher than normal for reasons other than just an elevated cholesterol, you should consider taking a statin. (Mine is, so I do, and I will continue to do so until better data becomes available.)
- I am not in favor of treating young people with elevated cholesterol with statins because of their very low risk of developing vascular disease in the near future. As the risk of a twenty-year-old having a heart attack is near zero, it is certainly not clear that using a statin to treat a high cholesterol level in this age group will be any more effective than starting treatment at fifty-five or sixty years old when the risk for heart attack is much greater.
And of course, you shouldn’t smoke, you should engage in moderate but consistent exercise, and you should achieve and maintain a healthy weight. I would add that you should eat a healthy diet, but unless you have been living under a rock for the past year, you know that no one knows anymore what constitutes a healthy diet. (Remember the headlines last month trumpeting, “Bring On The Bacon And Eggs!”?) So until we do have better, more reliable data on diet, moderation is probably the most prudent way to eat and, for that matter, to live your life, in general.
Taking a statin is a numbers game, and your best bet is to look carefully and thoughtfully at questions that address the efficacy of the drug for your particular situation. How much of a reduction in risk will there be for my particular risk factor group if I lower my cholesterol through the use of statins? How high is my risk for heart attack and stroke at this time in my life? What is the likelihood of side effects? Like most things in medicine, your own individual situation will be different from the person sitting next to you. Talk to your doctor, look at all the factors, and make your decision together.
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