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Lipitor, limits on its usage

Publicity about Recent Studies on the Cholesterol-lowering Statin Drugs: Misinterpretations


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Publicity about Recent Studies on the Cholesterol-lowering Statin Drugs: Misinterpretations

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There has been an extraordinary amount of news attention focused on recent studies concerning statins and heart disease, presented at the American College of Cardiology meetings in March and, in one case, published in the April 8, 2004 New England Journal of Medicine.


Without disparaging the importance of the studies themselves, we believe that spin-doctors and a scientifically uncritical news media have interpreted and stretched the findings in ways that go far beyond the actual data from the studies. A few examples will illustrate this:

Misinterpretation #1

Statins will prevent heart disease even in people who have not yet had a heart attack, stroke, angina or other kinds of cardiovascular disease if they have elevated cholesterol levels.

These recent studies are so-called secondary prevention studies. That is, the drugs were given to people who, in the case of one study, had been hospitalized with an “acute coronary syndrome,” meaning either a heart attack or high risk unstable angina.


Although there are some earlier studies involving people without previous evidence of cardiovascular disease (angina, heart attacks, bypass surgery, angioplasty or strokes), the evidence for treatment of these people, especially with cholesterol-lowering drugs, is weaker and is known as primary prevention. This is especially so for those people who do not have more than one of the risk factors listed below:

These risk factors include hypertension, diabetes, smoking, obesity, or a close family history of premature heart attacks or strokes. Other predisposing risk factors include a sedentary life style and a high-fat diet. It is likely that millions of people being given cholesterol-lowering drugs such as statins for primary prevention do not have more than one of these risk factors and are only being treated because of their total cholesterol or LDL cholesterol levels.

Thus, it is extremely important to look at the global risk of cardiovascular disease rather than focusing on just the blood pressure or just the cholesterol level. For primary prevention, it is usually most prudent to attempt to improve your cardiovascular risk through sensible programs of diet and exercise.

A case example of primary prevention involving someone who will, unfortunately, more times than not be recommended to start statins follows:

Ben is a 55-year-old man with a total cholesterol of 240 and an HDL of 50. However, his blood pressure is a normal 120/90 and he is neither a diabetic nor does he smoke. Ben turns out to have a 5-year risk of having a cardiovascular event (heart attack, stroke, etc) of only 5.1%, about one-half of the 5-year risk of over 10% that might merit drug treatment. It would be a good idea for Ben — or most people, for that matter—-to adopt the non-drug approaches to lowering his cholesterol discussed above, but since his global risk is as low as it is, drug treatment is not indicated even if his total cholesterol and HDL cholesterol stay the same.

In summary, these new studies did not even examine the role of statins in primary prevention. There are many people who have had heart attacks and strokes with elevated cholesterol levels who are not being aggressively enough encouraged and helped to lower their subsequent risk with diet, exercise or statins, the very kinds of secondary prevention the studies did address.

Misinterpretation #2

The study showed that atorvastatin (LIPITOR) prevents heart attacks.

The study published in the New England Journal of Medicine was designed primarily to see if the subsequent occurrence of a combination of adverse cardiovascular events was different in those taking a high or “intense” dose of atorvastatin (LIPITOR) versus those using the “standard” dose of pravastatin (PRAVACHOL). The combination included death from any cause, a heart attack, unstable angina (chest pain) requiring hospitalization, bypass surgery or angioplasty, or a stroke.

It is correct that the study showed that those taking atorvastatin were significantly (16%) less likely than those taking pravastatin to have any of the above events — and this is an important finding. However, there was not a significant reduction in heart attacks alone, death alone, or in the combination of death and heart attacks. The most significant reduction in the Lipitor group was in the subsequent occurrence of unstable angina requiring hospitalization.

Misinterpretation #3

The studies prove that atorvastatin (LIPITOR) is superior to pravastatin (PRAVACHOL).

As mentioned above, the purpose of the study was to see how intensive statin therapy (80 milligrams daily of atorvastatin) compared to standard therapy (40 milligrams of pravastatin) in people who had already had a cardiovascular event. There is reason to believe that the most important variable may be the intensity of the treatment rather than characteristics of the individual drugs.

Ideally, the study should have explored both the different drugs and different doses — standard or intense — of each.

Cholesterol-lowering Drugs For People 70 or Older

Aside from these recent papers, there is still some misinformation about the evidence for treating — in the form of primary prevention — elevated cholesterol levels in people over 70 years of age.

It is clear that the relationship between moderately elevated cholesterol levels and increased risk of heart disease is not as clear as people get older. As geriatricians Fran Kaiser and John Morely have written: “Given the uncertainty of the effects of cholesterol manipulation in older individuals, what should be the approach of the prudent geriatrician to hypercholesterolemia [elevated blood cholesterol levels]? In persons over 70 years of age, lifelong dietary habits are often difficult to change and overzealous dietary manipulation may lead to failure to eat and subsequent malnutrition. Thus in this group minor dietary manipulations such as the addition of some oatmeal [or other sources of oat bran or soluble fiber] and beans and modest increases in the amount of fish eaten, may represent a rational approach. Recommending a modest increase in exercise would also seem appropriate. Beyond this, it would seem best to remember that the geriatrician’s dictum is to use no drug for which there is not a clear indication.”

The use of cholesterol-lowering drugs in people 70 or older should be limited to patients with very high cholesterol levels (greater than 300 milligrams) and those who manifest cardiovascular disease (previous history of heart attack or angina, stroke). More recent reviews of this topic have reached similar conclusions: In one review, it was concluded that “unanswered questions include cholesterol treatment for primary prevention in the elderly, gender effect, and benefit of treatment in persons older than 70.” There are even questions as to whether elderly people who are hypertensive should have their cholesterol lowered by drugs. One review concluded that “Further trials are required before routinely suggesting that it is advantageous to lower cholesterol in an elderly hypertensive who does not have pre-existing evidence of coronary heart disease.”

What You Can Do

If your doctor recommends a cholesterol-lowering drug, especially for primary prevention, ask on what basis this is being done. This is especially true if you either are over age 70 or have no more than one risk factor.



The kind of conclusions that Public Citizen warns against 
MTSL No. 514 March 17, 2005, Medical Technology Stock Letter
Estimates have put the number of Americans with high cholesterol levels at around 39 million, and over a quarter of these individuals take statins to lower their cholesterol levels. (Statins lower cholesterol by slowing down the production of cholesterol and by increasing the liver's ability to remove the LDL cholesterol, or "bad" cholesterol, already in the blood.) To that end, the worldwide market for cholesterol-lowering drugs was about $24 billion last year (second only to hypertension drugs, at $35 billion in 2004), with the statin market alone garnering about $22 billion of that total. New evidence of the preventative health benefits of lowering cholesterol levels—with the use of statins, in particular—has helped to increase the number of patients who would be candidates for statin treatment, and new guidelines set last summer by the U.S. government for significantly lower cholesterol level goals for patients of moderate to severe risk for CVD have also helped to increase statin uptake. Taken together, these two factors should lead to a continued increase in the overall statin market. More recently, at the ACC meeting, data were reported which could help expand the statin market even further.
These data were from an over 10,000-patient study on Pfizer's Lipitor—not only the highest selling of the six available statins, at over $10 billion last year, but also the top-selling drug worldwide, period. In this trial, two different doses of Lipitor were evaluated—a 10 mg dose, and a more aggressive 80 mg dose. In a nutshell, the results showed that the patients in the higher-dose group achieved better results than their lower-dose counterparts, to the tune of a 22% reduction in the risk of stroke, heart attack, or other complication. There was a small increase in the risk of side effects, such as liver inflammation, in the higher-dose group, as well as a small increase in the number of non-cardiac deaths in the higher-dose group, but the increased number of deaths was not statistically significant, and no link could be found between the deaths and the higher dose. Plus, it is recognized that those on higher dose will need to be monitored regularly, and thus, while the increase in side effects sends up some warning flags, the results suggest that the benefits from higher-dose statins outweigh the small increase in side effects. Even in the context of a significantly more safety-aware PDA, these factors alone still provide support for treatment with higher-dose statins. One of the keys to the trial, however, was the patient population that was studied.
Current guidelines for cholesterol management suggesting lower LDL cholesterol target levels are based partly upon a previous study which had shown a similar benefit to the one discussed above for high-dose versus moderate-dose statin therapy. However, this study was conducted in very high-risk CVD patients. At that point, physicians still were not sure how achieving such low levels of LDL would benefit the much broader, lower-risk CVD patient population. In contrast, the Pfizer study included patients with more stable CVD. Thus, the results from the Pfizer study suggest not only the use of higher-dose statins, but in a broader patient population. Indeed, we expect this trend to continue.
 It is important to keep in mind, however, that the debate continues with regard to the best overall strategy for CVD management. We wanted to discuss these findings because they are sure to have a positive impact on what is already one of the largest selling class of drugs in existence. However, as we have discussed before in previous issues of MTSL, the LDL cholesterol inhibitors only serve to reduce bad cholesterol. They have little to no impact on the other side of the equation, HDL cholesterol, or "good" cholesterol. To that end, there are many who believe that raising HDL levels, or having a combination of the two, would be a part of the optimal treatment regimen. The most important fact of the matter is that the statins do not have the ability to reverse atherosclerosis—which is the build-up of plaque in the blood vessels, caused in great part, by higher cholesterol levels. Statins will continue to be used—and not only in more people, but likely in larger doses as well. However, to actually reduce the root of the main cause of CVD complications, we believe that a reversal of the process which leads to those complications will be part of the ultimate treatment regimen.