I am a bit, or more than a bit, skeptical of news about statin therapy because Lipitor, before it went generic, was responsible for over 6 billion dollars in revenue for Pfizer and since it went generic, Astra Zeneca is raking in more revenue than they did last year for their cholesterol drug, Crestor, at about 1.6 billion dollars. This kind of market influence is associated with significant influence on the attitudes of both physicians and patients through advertising and research support. I think that our love affair with statins cannot be separated from the fact that the sale of these drugs is a significant contribution to our economy.
Nevertheless, I recognize that statin drugs have contributed significantly to heart health since they were first released. Statin drugs were first released in 1987 after some false starts. The earliest statin caused muscle breakdown and killed some of the dog's upon which it was tested. Lovastatin, which was considerably less toxic was the first statin to be released. Statins reduce cholesterol by inhibiting an enzyme, HMG CoA reductase, but also stabilize the walls of blood vessels and reduce inflammation. In so doing, they reduce the risk of heart attacks, which are most commonly caused by obstruction of one of the coronary arteries by atherosclerotic plaques which rupture and form a clot that blocks blood flow to heart muscle. Inflammation is important in this process as well.
It has been known for decades that a high level of cholesterol in the blood is associated with increased heart attacks, as well as other conditions related to blood vessels such as strokes. Therapy to reduce cholesterol sometimes reduces the risk of these conditions, and many studies have been done looking at ways to reduce cholesterol. Not everything that reduces cholesterol reduces heart attack risk, though, and reducing the cholesterol and fat in the diet does not have a very significant effect on either overall cholesterol levels or on heart risk. Statins, though, do reduce the cholesterol level quite significantly and also appear to reduce the risk of various vascular events.
Heart disease is the leading cause of death in the US, so reducing the risk, even a little bit, has the ability to save many lives. Statins do reduce the risk of heart attacks, but for most people, only a little bit. In the patients most likely to benefit, those who have had heart attacks and so are at risk of further disabling recurrent heart attacks, as many as one in 29 patient who take statins for 4 years will avoid having a recurrent heart attack or death when compared to patients who do not take statins, as reported in a recent meta-analysis. For patients who haven't had heart attack, the chance that taking a statin will prevent having one is lower, for women 1 in 148 over 4 years. Statins do have side effects, from annoying symptoms like gas and muscle pains to more significant ones like memory loss, weakness and diabetes. In fact, the chance that a person with low to moderate risk of heart disease will get diabetes as a result of statins is quite a bit higher than the chance that he or she will be saved from having a heart attack. Dangerous and sometimes life-threatening muscle destruction with associated kidney failure is a rare but real side effect, which I have seen in practice. Significant side effects plague 18% of patients who take statins. A very good article, looking at controversies related to statin therapy, written by a professors from Harvard Medical School and UC San Francisco who question the mainstream belief in these drugs' effectiveness and safety, can be found in this week's New York Times. The vast amount of scientific data on statins is interpreted differently by different experts, but the way I look at it, in the patients at greatest risk for heart disease, 29 people have to take a statin for 4 years in order to save one of them from a heart attack. For patients at lower risk, the numbers are even less convincing. In the lower risk patients evaluated 148 have to take a statin for four years for one of them to not have a heart attack, which means that 147 patients take the drug, along with its side effects, for 4 years to no good purpose.
The major issue, beyond the economics and financial interests of drug companies, revolves around differing views of our mission as doctors, and also around differing experiences of physicians involved. If a person is a cardiologist, avoiding heart attacks is practically the only thing that matters. Cardiologists rarely see their patients for problems other than those related to their heart problems and don't face the day to day difficulties related to statin side effects. When a patient has muscle pains and cramping or stomach distress, he or she doesn't usually expect the cardiologist to resolve the problem. Cardiologists are great champions of statin therapy. Large organizations, such as the American Heart Association are also great champions of statins. The big picture for them is that a small effect on decreasing heart attacks, multiplied over millions of people who might take statins, means many lives saved. As a physician who treats individual patients, however, and as a person who may someday be a patient, I find it hard to advocate taking a drug with a very complex range of effects for a very small chance that it will make a positive difference. Even if we believe that our responsibility to the population is more important than to the individual, how do we assign value to patients whose lives are potentially saved against the much greater number of patients who feel just a little bit sicker because of a medication we prescribe?
The New Guidelines:
This week, to great fanfare, a new approach to prescribing statins was introduced. Many experts reviewed the extensive research, focusing on randomized controlled trials which are the most rigorous way to evaluate effectiveness. They were interested in finding the most effective and efficient way to reduce heart attack risk by influencing cholesterol. They looked only at statin therapy, since the vast majority of good research was on statins, as opposed to, say, fish oil or niacin or fiber or chelation therapy. They found that the most efficient way to reduce heart disease risk with statins was to check the cholesterol of all patients over the age of 40, and treat those with high risk of heart attack with either moderate or high doses of statins. The patients who should be encouraged to take statins are in one of 4 groups:
- Patients with LDL cholesterol greater than 189, who probably have a genetic condition that puts them at very high risk of heart disease.
- Patients between the age of 40 and 75 with diabetes, whose LDL levels are above 70 (very low.)
- Patients with prior heart attacks.
- Patients with a 10 year risk (see this risk calculator) greater than 7.5% of having a heart attack.
They recommended not checking cholesterol levels compulsively in order to reach certain set goals, though they do recommend checking the occasional level to see if the patient is actually taking the drug. It appears that treating to a target is very energy consuming and encourages us to add drugs that don't have evidence of effectiveness. In my experience, it can lead to focusing on numbers rather than on humans, but can also be the basis for conversations that might lead to more exercise and healthier living. Still, not focusing on cholesterol numbers will free us up to pay attention to issues of patient care that are probably more valuable. There were no good studies on treating patients over 75 with cholesterol lowering drugs, other than those with prior heart attacks, but it seemed likely that they would benefit. No recommendations are made for these folks, other than that they should discuss pros and cons with their physician.
Regarding side effects, the general implication of the article was that patients with muscle pains on statins should try to take them anyway, and that doctors should make sure to ask the patient before starting therapy if they had muscle pains so they could counter any complaints with the assertion that they had this before starting the drug. Having treated patient with statin therapy for years, I think that muscle pains are a very common side effect and can be disabling. I think that minimizing the importance of these symptoms by telling a patient that they should continue to take the medication that causes this will potentially reduce patients' quality of life and overall activity level. I am disappointed in the way this issue was handled.
One very interesting implication of this study is that an elevated cholesterol alone does not mean that a patient should be on a statin. Many people who are concerned about their health take a statin for an elevated cholesterol level, but their risk of heart attack is extremely low, so taking a statin will do nothing to improve their health. This is a positive development.
These new recommendations may be somewhat better than the rather random approach to cardiac risk reduction related to cholesterol that existed before, but are likely to overtreat patients without heart disease, resulting in patients whose health will be worse related to side effects, and who will be more dependent on the health care system because they will now be taking a drug. The guidelines will allow some people to stop taking their statins, which is good. I feel suspicious of the huge media coverage of this recommendation (most treatment recommendations get no news exposure) and I do expect that all of the free publicity will substantially increase the revenue of the companies that make statin drugs.