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Current Cholesterol Treatment Guidelines Don’t Reflect Medical Evidence

January 28, 2012

In the last year, three of my close relatives were prescribed statins; the class of drugs used to reduce cholesterol levels in the bloodstream. All three of my relatives had elevated readings of low-density lipoprotein (LDL) cholesterol (the bad kind) but no other risk factors for heart disease. Two of these relatives (my sister and a brother-in-law) are in their 50’s, are not overweight, maintain relatively healthy diets and exercise moderately. The third, my mother, is in her late 70’s, exercises daily and is in very good mental and physical health. No diabetes, little family history of heart disease, none are smokers.

I am not a doctor, but because I’ve written about medicine and health care for so long, people sometimes ask me for advice about medical problems and medications; most of the time I demur. But when my family members asked me what I thought about them undergoing drug therapy—potentially for many years, if not decades, in order to bring LDL cholesterol down to a target level, it was difficult to keep quiet. That’s because despite the widespread, almost reflexive, practice for doctors to prescribe statins, there is scant hard evidence that lowering cholesterol levels in otherwise healthy people will keep them from developing heart disease and extend their lives. This is especially true for women and people of both sexes who are over 65.

Questions about the wisdom of treating patients solely to achieve an LDL target are particularly important right now. A committee (the Adult Treatment Panel or ATP IV) convened by The National Heart, Blood and Lung Institute is currently revising clinical guidelines for testing and managing cholesterol. These guidelines were last released in 2002 (updated in 2004) and state that “recent clinical trials robustly show that LDL-lowering therapy reduces risk for CHD [coronary heart disease]. For these reasons, ATP III continues to identify elevated LDL cholesterol as the primary target of cholesterol-lowering therapy. As a result, the primary goals of therapy and the cutpoints for initiating treatment are stated in terms of LDL.”

Since those guidelines were released, more and more of us have been put on cholesterol-lowering drugs—current estimates are that one in four Americans over the age of 45 takes a statin daily. Heavy marketing of drugs like Lipitor (newly available in a generic form), Crestor and Zocor (available as generic simvastatin) to consumers, along with a concerted effort by drug companies to sell doctors on the relative cholesterol-lowering benefits of these drugs resulted in $17.1 billion in health care spending on just statins alone in 2009. Current spending figures are thought to exceed $20 billion. But along with this surge in treatment, there has been growing resistance among some researchers and cardiac specialists to the wholesale prescribing of statins. Studies have shown that for adults who already have heart disease, taking statins can have a clear benefit in preventing another heart attack. But for most everyone else, evidence of that clear benefit in preventing heart attacks and extending life is far less certain and can best be determined by considering an individual’s risk factors. As Rita Redberg, professor of medicine and director of women’s cardiovascular services at the University of California, San Francisco writes this week in the Wall Street Journal :

“For most healthy people, data show that statins do not prevent heart disease, nor extend life or improve quality of life. And they come with considerable side effects.” These include increased risk for developing diabetes, memory loss, muscle weakness, stomach distress, and aches and pains. “That’s why I don’t recommend giving statins to healthy people, even those with higher cholesterol,” she concludes.

Redberg is not alone in her treatment preferences. Recently, Harlan Krumholz, a professor of medicine at Yale’s School of Medicine and Rodney Hayward, professor of internal medicine at University of Michigan, wrote an open letter to the ATP IV committee members urging them to “follow a process that adheres closely to the scientific evidence, particularly the details of the clinical trials—which are abundant for lipid treatment.”

The letter, entitled “Three Reasons to Abandon Low-Density Lipoprotein Targets ” was published last week in the American Heart Association’s journal Circulation: Cardiovascular Quality and Outcomes and, according to Krumholz, is aimed at the larger physician community as well. It recommends a significant change from the 2002 guidelines:

“The evidence supports moving away from a target-based approach, a step that could launch a new era of guidelines in which treatment targets are replaced by a more tailored treatment approach (sometimes referred to as “individualized” or “personalized” care), which can improve patient outcomes while reducing harms and costs caused by overtreating low-risk/low-benefit individuals.”

How would treatment be determined under this “personalized approach?” First of all, most clinicians agree that lifestyle changes like following a low-fat, healthy diet and exercising—even moderately—can reduce the risk of heart disease significantly and should always be the first line of treatment. For those who have already had a heart attack, evidence does supports the use of a statin along with these lifestyle changes. But for all others, there is “an entire spectrum of risk factors” that need to be considered, says Krumholz—including whether a person is overweight, has diabetes, smokes, has a strong family history of heart disease, etc. Once a person’s risk of heart attack is better quantified, the next step is for a doctor to provide his patient with enough information to be able to make a decision about treatment.

Here we get to the heart of informed decision making. A key part of this process is providing patients with an important figure called “number needed to treat.” In his ground-breaking Business Week article on the cholesterol controversy , John Carey explains how this figure illustrates the relative benefits of statins. In the small print of Lipitor’s own ad is the following statement: “[I]n a large clinical study, 3% of patients taking a sugar pill or placebo had a heart attack compared to 2% of patients taking Lipitor.”

What this really means, according to Carey, is that even in an industry-sponsored study where many participants had risks factors like high blood pressure or were smokers, there was only one fewer heart attack per 100 people among those taking Lipitor. “So to spare one person a heart attack, 100 people had to take Lipitor for more than three years. The other 99 got no measurable benefit. Or to put it in terms of a little-known but useful statistic, the number needed to treat (or NNT) for one person to benefit is 100.”

Evidence from other studies puts the number needed to treat for statins at 250 and up for lower-risk patients even if they take it upwards of five years. In the Business Week article Dr. Jerome R. Hoffman, professor of clinical medicine at the University of California at Los Angeles asks; “What if you put 250 people in a room and told them they would each pay $1,000 a year for a drug they would have to take every day, that many would get diarrhea and muscle pain, and that 249 would have no benefit? And that they could do just as well by exercising? How many would take that?”

Moving the national cholesterol treatment guidelines away from a strictly LDL target approach (i.e. drug therapy starts when LDL cholesterol is above a certain level) and towards a less mechanistic, more risk-based one would have a number of positive effects. First of all, it will prevent overtreatment, reducing harmful side-effects like diabetes, memory loss and muscle pain while also saving health care dollars. Secondly, according to Krumholz, it will avoid under-treatment of patients who have high cardiovascular risk factors but low LDL. This could save lives.

Finally, measuring the effectiveness of a drug only by how well it reduces LDL cholesterol leads to the approval and sale of expensive new therapies that have little benefit in preventing heart attacks or death. Take the case of Vytorin, a combination of an off-patent statin and another cholesterol-lowering drug called Zestia that is sold by Merck-Schering Plough. Vytorin, which had $4.6 million in sales in 2009 and is covered by Medicare, costs four times more than a generic statin, yet has never proven more effective in preventing heart attacks or death. What it did do is lower LDL cholesterol 20% more in some patients than the generic statin. I wrote about how Merck-Schering Plough buried negative studies about Vytorin, paid cardiovascular experts to tout the drug, and is “relentlessly pursuing positive trial results” in a post for HealthBeat. These results, which will indicate whether Vytorin is better at preventing heart disease than a generic statin aren’t expected until at least 2014.

In the end, the idea that lowering cholesterol to a target level will help prevent heart disease and death in all people is not supported by scientific evidence. The case is building for a more nuanced national guideline that considers risk and a personalized approach to treatment that, according to Krumholz, “is estimated to save about 100,000 more quality-adjusted life years annually while having fewer people on high doses of statins than a treat-to-target approach.”

Right now, this message is not getting through to most physicians. After all, they are following the recommendations of the National Cholesterol Education Program. But for me, it’s hard to keep quiet when my mother calls me, her voice filled with worry, and tells me that her cholesterol is high and her new doctor wants to put her on a statin. I tell her, “you’re 79, you exercise regularly, your diet is very healthy, your mother and father lived to 90 and 86 respectively, and this is the first time a doctor has ever been concerned about your cholesterol.” I send her articles from science journals and the popular media. I advise her to bring this material to her doctor and discuss her real risk of heart disease. I wonder what kind of arrangement her doctor’s practice has with drug companies; I tell her “this is your choice, make an informed decision.”

Let’s hope the national cholesterol treatment committee moves toward recommending just this kind of what Krumholz calls a “simple, tailored treatment approach” to drug therapy that “is based on a person’s overall 5- to 10-year cardiovascular risk regardless of LDL level.” Not only does this approach reflect the best medical evidence, but it promises to reduce overtreatment and excess health care costs while moving treatment into the realm of patient-centered care.

  1. I think some higher responsibility for reporting the real side effects and their frequencies would also help curb so much purely “preventive” treatment use. If you notice in the statin adds, they always talk about the rare muscle pain side effect that can be a sign of danger. I wonder just how rare such side effects really are? I have a suspicion that some level of muscle pain and issues is actually very common although maybe not the worst level possible of such pain!!

  2. lhf permalink

    One really serious concern here is the recent recommendation – I think by the pediatricians’ professional group – that children be tested for high cholesterol levels and if found, be prescribed a statin.

    When my children were in elementary school in the 1980s, a local pediatrician volunteered to test all of the children’ s cholesterol levels. Both my kids, neither overweight, tested above normal. A low fat diet was recommended by him. My pediatrician, bless her heart, said not to do that. She said children need a certain amount of fat in their diets for normal brain development. So we followed her advice.

    My children today, in their 30s, are not overweight and have low normal cholesterol levels. I always had the same, but at 67 my total has edged up, however, the increase has been almost entirely in HDL. Ditto, my 74 year old husband. Neither of us is overweight, but every year we have to have an argument with our doctors over statins, which we have always refused.

    Oh – and not mentioned in your article, but another factor, is one’s triglyceride levels. I think they measure total blood fats? Ours are both low.

    I learned alot from the hormone replacement fiasco. The list of horribles I would get if I didn’t get on them before menopause was long and scary. I resisted and that was ultimately proven to be wise. I don’t take any drugs now that have not been out there long enough to be well tested and of proven benefit.

  3. wkj permalink

    See also the opinion piece “Ritalin gone wrong” in today’s NYT which addresses analogous issues.

    One particularly interesting point in the NYT piece is the fact of drug resistance–apparently after long-term usage of ritalin it can take a larger dose to do the job. Is that also an issue for statins?

  4. LHF–You are right to be concerned about children and statins, especially because most of the children with high cholesterol are also obese and at risk of Type-2 diabetes. They are children who would benefit most greatly from lifestyle changes (diet and exercise) and should not be put on drugs tested solely on adults. As for triglyceride levels, a recent study found that adults with high levels of these fats but had low cholesterol levels benefited from statins. This finding justified putting a whole new cadre of people on statins without cholesterol being an issue. Of course with a more personalized course of treatment, this would be a factor in deciding whether someone wanted to go on a statin or not.

    WKJ–When I read the “Ritalin Gone Wrong” op-ed in the Times I also saw this as an analogous issue to cholesterol and statins. Thanks for pointing this out. The dearth of basic scientific understanding about the cause of both heart disease and ADHD leads to an frustrating overtreatment of some and an under- or mis-treatment of others. As for statin resistance, I haven’t seen anything about resistance developing after months or years of drug treatment, but I did find information about people who seem to be resistant to the LDL-lowering effects of statins from the very begining. This article from Duke researchers points to a possible genetic explanation:

  5. Naomi — I have no opinion on whether your relatives should take a statin. It’s a personal decision. It might help them to use an online risk calculator to calculate their 10-year risk of cardiovascular disease. (By the way, at least your BIL and mother do have another risk factor: age. Age over 45 in men and over 55 in women is considered a risk factor. If your sister is over 55 she also has a risk factor.)

    For people who have not been closely following the debate, Rita Redberg’s views and Jerome Hoffman’s views are not at all the same as those of Drs. Krumholz and Hayward. Dr. Redberg is opposed to primary prevention in most cases. Krumholz and Hayward are not. They simply argue that using global cardiovascular risk and fixed doses of statins is more effective and efficient than the treat to target paradigm. Dr. Hoffman is opposed to primary prevention.

    Hayward et al. Optimizing Statin Treatment for Primary Prevention of Coronary Artery Disease. Annals of Internal Medicine. 2010;152(2);69-77.

    From reading your post, I am confused as to whose views you agree with. It certainly cannot be all of the people you are talking about. If you agree with Krumholz and Hayward then you must disagree with Redberg and Hoffman. It would help me if you could clarify.

  6. Marilyn, I believe first and foremost that statins are vastly overused in this country and that despite what you write about age being a large risk factor for heart disease, studies have yet to show that statins benefit women over 65 who have elevated cholesterol but no symptoms of heart disease.
    Not only that but the risk of diabetes appears to be raised in post-menopausal women taking statins:
    As to whether I agree with Dr. Redberg vs. Dr. Krumholz, I think that they represent two views on a spectrum that is recommending moving away from mechanistic LDL levels as being the target of treatment. Redberg may be opposed to preventive use of statins for many patients while Krumholz prefers a more personalized approach based on number-needed to treat but both agree that the current recommendations are not reflecting the scientific evidence.

  7. Naomi

    I stated very clearly that I was not saying your relatives or anyone else should take a statin. I simply said that age is a risk factor for heart disease. And I did not use the word “large.” Please, please do not put words in my mouth. Thanks very much.

    I have blogged on this issue as well.


  8. cmac611 permalink

    I’m surprised that better information isn’t available on this subject … I’ve researched it and found that LDL has two ‘patterns’ A is neutral or good cause it’s a larger molecule and will ‘float’ in the blood, pattern B is bad as it’s small and will settle. Regardless, LDL is a ‘calculated’ value so how do you know what pattern you may have? Low Tri’s and high HDL is associated with pattern A. I’ve learned to ignore LDL and focus on low Tri’s (mine is 65). Both my wife and I have improved our health with diet, exercise (i.e., lifestyle) changes. Yes, it’s hard work and takes discipline, but I’ve chosen this route versus participating in our broken profit driven sick care system! I love everything you’re doing to try and fix this mess (if it’s even fixable), however, our society seems to have forgotten something called ‘personal responsibility’ … I don’t know how else to explain our epidemic of preventable diseases that is a driving force behind our out of control health care system. Sorry for the ‘soap box’ … appreciate everything your doing 🙂

  9. Doctorsh permalink

    I agree that statins are way overused.
    I rarely use them in my practice, and usually recommend people get off them for reasons you sated above.
    I do take exception to your recommendation about lowfat diets being the answer.

    Lowfat diets are NOT the answer for a large majority of people.

    There are all types of fats, some natural, there’s artificial. Distinguishing the differences in each individual makes the most sense.

    But getting back to the theme of your overall blog, as long as you drive docs into third party corporate or govt medicine, the docs will no longer think, they will just be automatons and do whatever the biased clinical guidelines tell them to do.

    How bout looking at the nnt for screening colonoscopies in a future post. You might be surprised what you find.

    • Vast majority of Drs are Government Employees who MUST follow guidelines of get fired!

      Anyone know the NNT for the new Statin Livalo – pitavastatin?

      Thanks Clare in Tassie

  10. Howard C. Berkowitz permalink

    Going a step farther, in the primary practice I’m now leaving, one major insurer insists that the practice demonstrates, to its satisfaction, that guidelines such as this one must be followed for all patients. To be explicit, the insurer requires that the guidelines be applied even for patients it does not insure, or there may be financial disincentives to the physician. Apparently, some number of patients may be noncompliant.

    I need statins to be in reasonable compliance with HDL levels. With an HDL to total ratio around 3.4, however, the guidelines call for additional medication to further lower my LDL.

  11. Low Fat diet will not do anything much to help as the vast majority of cholesterol is made in the liver. Eat less cholesterol and the liver will make what it deems the body needs to deal with the specific issues. Cholesterol is what the body makes to address the inflamatory process. Find why there is inflammation and treat that – then the body will automatically make less cholesterol. These drugs kill people….. slowly and cruelly

  12. lhf permalink

    This is a great blog – I hope you can keep it up. I don’t always agree with the positions taken, but the debates are always interesting.

    Two books on the subject of this thread are “Overdiagnosis” and “Rethinking Aging.” I’m still waiting for the second book to arrive in the mail, but I think it pretty much debunks the notion that age is a risk that should result in treatment. Aging is not a disease, it’s a stage of life. Yes, your risk for dying certainly increases, but the question remains whether it makes sense to “treat” it.

    I’ve watched as my friends in their 60s and 70s add more and more drugs. It’s not only the drugs to treat specific conditions, but the conflicts among them that lead to endless experimentation to find a proper assortment and then the additional drugs to treat the side effects. Pretty soon you are eating a dozen pills a day out of a little box designed to help you keep track of them.

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  14. Statins may help in reducing cholesterol levels but as you mentioned that there is hardly any evidence to prove that it will prevent otherwise healthy people from getting diabetes or extend their life span. Further more the statement of Rita Redberg in wall street journal that statins do not help prevent diabetes or extend life and they also have some serious side effects makes one doubtful as to what is better for him – whether one should take statins or avoid them!!

  15. While many aspects of these new guidelines concern me, one of the biggest is the concerns I have is the recommendation to use statin in people with diabetes. First off, statins can actually contribute to type 2 diabetes. In fact, last year the FDA began requiring statin manufacturers to put a diabetes warning on their labels. So giving statins to people who already have diabetes doesn’t make sense.

    Plus, the data demonstrates that for men with diabetes statin drug use can lead to calcification of the coronary arteries. There’s also documented evidence that cataracts are more common in those taking statin drugs. And since people with diabetes are already more prone to cataracts, the use of statins for this population can be harmful.

    A far better intervention for people with type 2 diabetes, or pre-diabetes, is lifestyle changes—including diet therapy; weight reduction; avoidance of sugars; exercise; use of raw foods, particularly vegetables; and targeted nutritional supplements.

    On my blog I actually went through each of the guidelines one-by-one outlining my concerns:

    Dr. Stephen Sinatra
    Board Certified Cardiologist
    Assistant Clinical Profession, Connecticut University School of Medicine

  16. Adrian Janz permalink

    Smiles filled the back of the aircraft Celesta

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