More than 20 states have passed so-called "Right-to-Try" laws that give terminally ill patients access to experimental drugs. What bypassing the F.D.A. could mean for clinical trials, treatment outcomes and patient safety.
In the 30 years since they were approved by the FDA, cholesterol-lowering drugs called “statins” have cut in half Americans’ death rate from heart disease. Today, more than 20 million Americans take a statin drug like Lipitor or Zocor. Many of these people have high cholesterol but no sign of heart disease. There is growing evidence that statins provide little or no benefit for healthy patients and can trigger dangerous side effects. And new studies question whether there really is any link between cholesterol levels and heart disease. Diane and a panel of guests discuss the latest cholesterol research and what it means for heart disease prevention.
- Dr. Barbara Roberts director, Women's Cardiac Center at Miriam Hospital in Rhode Island; associate clinical professor, Brown University's Alpert Medical school; author of "The Truth About Statins."
- Dr. David Pearle clinical cardiologist at Georgetown University Hospital, and professor in the department of medicine at Georgetown University.
- Sharon Begley senior health and science correspondent at Reuters and contributing writer to The Saturday Evening Post; author of "Train Your Mind, Change Your Brain"; and the co-author (with Jeffrey Schwartz) of "The Mind and the Brain."
MS. DIANE REHMThanks for joining us. I'm Diane Rehm. One-quarter of Americans over the age of 45 take some type of cholesterol-lowering drug. But new research questions the benefits of these statins for heart-healthy patients and raises doubts about whether there is any link between cholesterol levels and cardiovascular disease. Joining me in the studio to talk about the latest research and what it means for heart disease prevention: Dr. Barbara Roberts of Miriam Hospital and Brown University and Dr. David Pearle of Georgetown University.
MS. DIANE REHMJoining us from a studio in New York City, Sharon Begley of Reuters. I hope you'll feel free to join us with your own questions, 800-433-8850. Send us your email to email@example.com. Join us on Facebook or Twitter. Good morning to all of you.
DR. DAVID PEARLEGood morning, Diane.
DR. BARBARA ROBERTSGood morning, Diane.
MS. SHARON BEGLEYGood morning, Diane.
REHMAnd, Sharon Begley, if I could start with you, you recently wrote a piece for the Saturday Evening Post about cholesterol. And you opened with a story about a doctor who does not let anyone measure his own cholesterol. Why is his story so important?
BEGLEYHe is a physician in his 70s. He leads a healthy life. He exercises. He eats right. And he believes, based on the evidence that has been published in the scientific and medical literature, that knowing your cholesterol is not really very useful, and the reason is he has not had any heart disease, never had a stroke, never had a heart attack. And the emerging research is suggesting that for people like him, again, people without pre-existing heart disease, lowering your cholesterol is not very helpful in terms of either extending your life or reducing the risk of heart disease or stroke.
BEGLEYAnd therefore, he basically doesn't want to know. Knowing is not something that would be actionable. It's not something that his physician would look at and say, well, the physician might say, OK, take a statin. But Dr. Hadler of the University of North Carolina believes that that would not be very helpful to his health, so he basically has made the decision, don't tell me.
REHMSo -- but, Sharon, you've got, like, 20 million Americans now on one drug or another to help lower cholesterol. Does he believe and do you believe, having done your research, that these cholesterol-lowering drugs for people who are otherwise healthy are not necessary?
BEGLEYWell, I would say it doesn't matter too much what I believe. But I'll describe just very briefly what their research is showing, namely that for primary prevention.
BEGLEYThat's the buzzword for what we're talking about as you just put it, Diane, people without existing heart disease. For primary prevention, statins seem to offer very, very little benefit. I don't want to get lost in the weeds here...
BEGLEY...in all the numbers that are relevant here, but just let me throw out just a couple. In one of the key studies that examined whether statins are helpful, are beneficial to people without pre-existing heart disease, three out of every hundred -- again, without pre-existing heart disease but with high cholesterol -- who took an inert pill suffered a heart attack, three out of 100. Two out of every hundred of the same kind of people taking Lipitor suffered a heart attack.
BEGLEYSo there was a reduction, and if you want to roll the dice and think that you are the one person out of 100 who would have had a heart attack without a statin and will not have it with a statin, you know, that's a personal choice. But, of course, on the other side of the ledger, no medication is without side effects, so you, of course, have to factor those in as well.
REHMSharon Begley, she is senior health and science correspondent for Reuters. Her article for this month's Saturday Evening Post talks about cholesterol and heart disease. Turning to you, Dr. Barbara Roberts, as you look at this debate, how do you see it?
ROBERTSWell, I agree with Sharon, and I would like to make the point that the benefit, the "benefit" in women for primary prevention is even lower. If you analyze the three big primary prevention trials that included any women and you look at all of the endpoints -- and endpoints is a very neutral term that doctors use to describe really bad things...
ROBERTS...like heart attack, stroke, death. But some of these trials included endpoints that weren't particularly hard endpoints. I always say that death is the hardest endpoint.
ROBERTSWe doctors don't often get death wrong. We're pretty good at diagnosing death. But some of these studies included things like hospitalization for unstable chest pain syndromes or the need for revascularization, and some of these studies were done in countries as different as Bulgaria and the United States. And I don't know this for a fact, but I suspect that a lot fewer stents and bypass operations are done in Bulgaria than the -- in the United States.
ROBERTSDespite that, if you look at all of these endpoints in women, the risk was lowered from 2.1 percent to 1.3 percent. If you factored out those softer endpoints, and we're talking -- the denominator here is almost 10,000 women -- the risk of having either a heart attack or dying of heart disease was 0.9 percent in women on placebo and 0.8 percent in women on statin. And that's clearly...
REHMSo not much different.
ROBERTS...not statistically significant.
ROBERTSYou would have to treat 1,000 women for about three years to lower the risk of heart attack or dying of heart disease.
REHMBarbara Roberts, M.D., is director of the Women's Cardiac Center at Miriam Hospital in Rhode Island. She is associate professor at Brown University's Alpert Medical School. Her book is titled "The Truth About Statins: Risks and Alternatives to Cholesterol-Lowering Drugs." Turning to you, Dr. David Pearle, how often do you use statins? And do you see a measurable difference in how the patients you treat with statins have a favorable outcome?
PEARLEWell, Diane, of course, I use them every day as every cardiologist does. I think the world of Dr. Hadler -- he and I were medical school classmates at Harvard 100 years ago. But the issue in his statement as Sharon described it is what do you mean by pre-existing heart disease, the majority of heart attacks, the majority of sudden death attributable to coronary artery disease or in patients who did not have previous symptoms?
PEARLESo just because someone does not have symptoms does not mean they're at risk. We have a lot of ways of identifying people who are at risk: people with diabetes, people who smoke cigarettes, people with a strong and positive family history, people who don't exercise. So symptom is a very crude way to say, do you have pre-existing heart disease? And we know that the sudden deaths and heart disease and heart attacks are not, you know, sudden events like breaking your leg or something.
PEARLEThey are the kind of a culmination of a long period of progressive sub-clinical development of atherosclerosis. So if I really knew that I was not destined to have coronary artery disease or I had no risk factors or there are some other more sophisticated tests we can use to pick up an early phase of atherosclerosis, I would not want to take a statin. But if I fell into a risk group, then I think the benefits of statin and preventing something bad from happening to me two or five or 25 years later become very important.
REHMDr. David Pearle, he is clinical cardiologist at MedStar Georgetown University Hospital, professor in the Department of Medicine at Georgetown University. We do invite your questions and comments, 800-433-8850. Send us your email to firstname.lastname@example.org. Dr. Roberts, are you saying that even the benefits of statins with existing heart disease do not outweigh the risks of taking those statins?
ROBERTSNow, we're talking about what we call secondary prevention.
ROBERTSIf you have established vascular disease -- and I analyzed five of the biggest secondary prevention trials, and I looked at the outcomes in men and women. And if you look at these five trials, which included over 33,000 men, the event rate dropped from 25.5 percent in men on placebo to 19.5 percent in men on statins. So there's a 6 percent absolute risk reduction. But when you read these trials and you read the headlines, they never give the absolute risk reduction.
ROBERTSThey give the relative risk reduction which, in this case, would be 6 percent divided by 25 percent, which is obviously a much bigger number. If you look at the benefit in women, the event rate dropped from 17 percent in women on placebo to 13.9 percent in women. So men had twice the benefit in women. In fact, women on placebo in those five trials had a lower event rate than men on statins. So what I'm saying is, yes, statins give you a small absolute risk reduction, but the risk reduction in women is less than men. And women have more side effects to statins from men.
REHMWhat are those side effects, Dr. Roberts?
ROBERTSWell, we've known for a long time that statins can affect muscles. Statins damage muscles. And we used to tell patients if they complained of muscle pain on statins, well, we'll check a muscle enzyme. And then we would check an enzyme called CPK. And if the CPK was normal, we'd say, no, it's not the statins. You don't have to worry. Well, there have been studies done using muscle biopsies that have shown statin damage even if the CPK is normal.
REHMDr. Barbara Roberts, and her book is titled "The Truth About Statins." We'll take a short break here and be right back.
REHMAnd we're talking in this hour about cholesterol-lowering drugs, to what extent they really provide protection when an individual is not at risk for heart disease or is at risk for a heart disease. Just before the break, Dr. Roberts, you were talking about women and their benefit from statin seemed to be less than that of men. Why do you believe that so?
ROBERTSWell, that -- are what -- that's what the data showed.
ROBERTSBut I think part of the reason is that LDL, the so-called bad cholesterol, is not as important a risk factor in women as it is for men.
ROBERTSMany years ago, when David and I were young doctors -- granted that was back in the Dark Ages -- but I was involved in the Lipid Research Clinics program at the NIH. And we gathered over 2,500 men and over 2,000 women who were healthy, between the ages of 40 and 60, and followed them for an average of 19 years.
ROBERTSAnd everybody got a total cholesterol, an LDL cholesterol, a non-HDL cholesterol and the HDL cholesterol, which is the so-called good cholesterol. In men, every one of those things as they increased, or when HDL decreased, significantly increased the risk of the hardest endpoint, which is cardiac death. In women, even at LDL levels of over 190, there was no statistically significant increase in a woman's risk of dying of heart disease.
ROBERTSIn women, it's far more important. It's far riskier to have high levels of triglycerides and low levels of HDL, the good cholesterol.
REHMSharon Begley, we've been hearing an awful lot lately about the debate now over good cholesterol, bad cholesterol, and whether there truly is a difference. What does your reporting on this show?
BEGLEYWell, as the names would suggest, the idea was that high cholesterol -- sorry, good cholesterol is protective against heart disease, while bad cholesterol, LDL, is a risk factor for heart disease. So the conclusion seems simple. Well, let's do something to raise the good cholesterol, especially in people who are at risk for heart disease. Unfortunately, medicine keeps, you know, showing us that the human body is not as simple or straightforward as we might have expected or hoped.
BEGLEYSo a recent study showed that, in fact, when you raise good cholesterol in people, in fact, you do not really reduce their risk of a bad outcome, a heart attack, heart disease or death, which raises the question, well, then might good cholesterol not be so much something that we can manipulate in order to benefit people, but might it instead be what's called a marker? In other words, it's there. It's reflecting something else.
BEGLEYMaybe it's reflecting that people are eating healthy. Maybe it's reflecting that people are exercising right. Maybe it's reflecting something genetic that factors into your risk of having heart disease. But in any case, it looks like the outside manipulation of good cholesterol through drugs, even simple ones like niacin, is not as beneficial as, you know, the pen and paper calculation might have suggested.
REHMDr. Pearle, with treating patients as you do, all of this changing research must be factored in to how you treat those patients.
PEARLEWell, absolutely. I mean, medicine changes. We learn. But I don't want to be nihilistic here. The death rate from cardiovascular disease has decreased about 75 percent since 1968, 75 percent, which happens to be the year I graduated from medical school. I don't like to take all of the credit, but facts are facts. So a lot of what's been learned is not wrong and not open to question. We learn more.
PEARLEThe LDL story, the statin story is pretty well-established. The issue on statins is not their effectiveness, but who should we be using it in. And, clearly, the more -- there is much more benefit to use it in patients with high cardiovascular risk. The HDL or good cholesterol story is a much more complicated story. It's a very important story for every person who -- in the United States who has a problem with LDL, there's another person who has a problem with HDL. It's just not so clear what we need to do to influence it in a favorable way because HDL is really a family of proteins and so on.
PEARLESo it depends on how you raise the HDL, and the story is not completely in yet. As Sharon says, the HDL may be a marker. I mean, you know, Tiger Woods wears a red shirt on the last day of a golf tournament. If I wore a red shirt, I probably wouldn't play golf all that well. The red shirt is not the reason Tiger Woods plays well. But there's something very important in the HDL story, and there's a lot of emerging studies and evidence. We're just not there yet in the way we are with LDL.
REHMAnd, Dr. Roberts, just before the break, again, you were talking about the side effects of the statins. You talked about muscular weakness. There are others, I gather?
ROBERTSYes. And the one that really concerns me the most is the effect on cognitive functioning, and this we never learned from randomized control trials. In fact, the first I heard of it was from a young woman patient of mine. She's only in her 40s. She had type 2 diabetes, so she was on a statin because, basically, the guidelines say everyone with diabetes should be on a statin. And about four of five years ago, she said to me, Dr. Roberts, do these statins cause memory problems because ever since I started this medicine, I can't remember anything.
ROBERTSAnd I said, you know, I don't know, but I'll keep my ears open. And I began hearing this more and more from patients. In fact, there's a story that was written up by one of my patients in my book. This man is a professor of mathematics at an Ivy League university, and he got to the point where his memory was so poor that he couldn't do his research. He didn't publish a paper for four or five years. He couldn't supervise his fellows, and he was extremely depressed.
REHMAnd yet he was alive because he was on statins?
ROBERTSNo, he -- I didn't put him on a statin. He was a healthy man whose cholesterol was a little bit elevated, and his primary care doctor put him on statins.
ROBERTSHe stopped -- and he also developed severe muscle weakness.
ROBERTSHe stopped the statins. And, gradually, his memory came back, and it all cleared.
REHMNow, Dr. Pearle, have you encountered any of these kinds of problems?
PEARLEYes, I agree with what Dr. Roberts says. But I would like to provide a slightly different perspective. Statins have been with us for about 25 years now. They've been studied in enormous studies, ranging from about five to 30,000 patients. They're effective and appropriately selected patients. And the side effect profile is relatively benign compared to anything else we have on the market to take specifically the issue of cognitive dysfunction.
PEARLEYes, I have had patients who go on it. They have memory problems. They feel their thinking is fuzzy. You stop it. They get better. But if you look at these enormous studies, for example, the JUPITER study, cognitive dysfunction does not even show up as being worse in the statin-treated group than it does in placebo.
PEARLESo there's no doubt in my mind that, on an anecdotal basis, there are patients who don't tolerate it. But there may actually be a sort of a multifactorial effect. It may be a lot of older people who have cognitive dysfunction it's because they're having little mini strokes, and it may be the statins helped those people, and yet hurt the people who notice this short-term side effect. So there's no question in my mind it's real.
PEARLEBut, quantitatively, I think these are among the most effective and safest drugs we have. There are no perfect drugs, and they have to be used in appropriate people. But, you know, they're relatively safe compared, say, to a lot of drugs we sell over-the-counter. Like, Motrin or Aleve and the non-steroidals, have, I think, a much more side-effect profile that are over-the-counter than do statins.
REHMSharon Begley, do you want to comment?
BEGLEYI'll just simply add that when the story that you referred to, Diane, when I was finishing the reporting and research for that, the FDA announced what are called importance safety changes in the labels required on statins. As the physician just explained, beginning immediately, the labels do have to warn patients that the drugs have been reported to cause certain cognitive effects, including memory loss and confusion.
BEGLEYAnd the labels will also have to warn that increases in blood sugar, hyperglycemia, have also been reported. And then the FDA had to serve odd phrasing. It is aware of studies showing that statins may increase the risk of type 2 diabetes. So, as Dr. Pearle just said, absolutely, you know, everything is relative, and statins' deleterious side effects are nothing like some -- those of some of other drugs.
BEGLEYBut then we just get back to the individual patient and figuring out that individual patient's risk and his or her tolerance for risks and benefits. Is the fairly small decrease in your risk of having a heart attack or dying in the next five years, is it worth it to you for the very real risk of these side effects? And that's something that really requires a long conversation with your physician if you can get the time with him or her.
REHMAt which point, Dr. Roberts, are physicians prescribing these statins? Do you think they're doing it too frequently? Do you think the numbers regarding cholesterol are changing so much that too many physicians are prescribing them too early? What's your thinking?
ROBERTSAbsolutely. Not a week goes by that I don't see a young person with no other risk factors who comes to me because their primary care doctor prescribed a statin because their cholesterol number was one or two points above the so-called...
REHMWhat is the so-called norm at this point?
ROBERTSWhat is the -- well, the normal depends on how many other risk factors you have, and that's a whole other issue. But if you're a healthy person, for example, then your goal for LDL -- if you have 0-to-1 of the risk factors -- is under 160. And the guidelines currently say consider drug if your LDL is over 190. But I see women, in particular, in their 30s and 40s being put on statins because their LDL is 161 or 162 without any dietary intervention and no other risk factors.
ROBERTSBut I wanted to get back to something that Sharon mentioned about diabetes, and David mentioned the JUPITER trial, which was one of the trials that showed an increased risk of diabetes. The JUPITER trial was planned to last for five years. It was stopped prematurely after only a median follow-up of 1.9 years.
ROBERTSFor "benefit." But the benefit that they claimed when they first announced the study, they claimed that it had a benefit on cardiovascular mortality. When the paper was finally published, that benefit was not apparent.
REHMNow, you had a very personal experience with your husband. Would you talk about that?
ROBERTSYes. In 1995, we took a trip to Italy, where, basically, my husband Joe was overdosing on prosciutto di Parma every night.
ROBERTSAnd my husband loves to work out. He loves to run, and he loves to weight lift. And he came home, and his primary care doctor checked his total cholesterol. It was over 300. So we started him on a statin.
ROBERTSAnd he developed severe muscle pain, which interfered with his ability to work out. Well, Joe was tried on every statin that's available in the United States, and every one of them caused severe muscle pain. So I did a lot of research and put us both on the Mediterranean diet, which I would love to talk about more because the Mediterranean diet has better outcomes than any statin.
REHMThan the statins.
ROBERTSAnd with the Mediterranean diet, his cholesterol numbers are in an acceptable range, and now he can work out to his heart's content.
REHMDr. Barbara Roberts of the Miriam Hospital in Rhode Island. She's author of a book titled "The Truth About Statins." And you're listening to "The Diane Rehm Show." I'm going to open the phones now, 800-433-8850, to Durham, N.C. Good morning, Fred. You're on the air.
FREDGood morning, Diane.
FREDI've told you how much I've enjoyed the show, and I enjoy your show almost every morning.
FREDI had a quick question, which has been touched on by Dr. Roberts and Dr. Pearle, which is that, as you attempt to find an appropriate cholesterol level to prescribe statins, that number keeps going down. It was originally intended primarily for patients with hypercholesterolemia. The highest number is well above 250. And now people are trying to use it when people have numbers around 150. So it's part of the problem that it's being over-prescribed in situations where it's really not applicable.
PEARLEWell, fair enough, the numbers have changed. The guidelines emphasize that the target LDL depends on your risk profile. I'm an interventional cardiologist, so I wind up treating a lot of patients with established severe coronary disease. For a long time, the target LDL for those patients was below 100. And we now have studies -- they're somewhat controversial -- that there is incremental additive benefit of shooting for a target less than 70.
PEARLESo the higher the risk the group you fall into, the lower the target should be. At the other end of the spectrum -- let me just emphasize here a point that Dr. Roberts made before, the distinction between secondary prevention and primary prevention. Patients with known coronary disease, the benefits are clear-cut, not controversial. We can debate a little bit what the target should be.
PEARLEThe area of debate is primary prevention. But I would further divide primary prevention into those at relatively high risk versus those at lower risk. And at patients at lower risk, the target might be below 160 or 130, which are two figures used in the current guidelines. We don't have to shoot quite as low in patients who fall into lower risk.
REHMDr. Roberts, do you want to comment?
ROBERTSWell, the primary prevention trials that we've mentioned were all in high-risk primary prevention trials. One of them, the ASCOT-Lipid Lowering Arm, was done in people who had high blood pressure plus three other risk factors. So even in this high-risk primary prevention group, the benefits were modest in men and nonexistent in women. The other thing I want to bring up is the subject of avoidable care. I attended a conference in Cambridge in April -- Cambridge, Mass. -- called Avoiding Avoidable Care.
ROBERTSThe United States spends twice as much as any other developed country on health care. And yet in many aspects -- whether you look at life span, life expectancy or maternal mortality -- we lag behind other industrialized nations. We spend about $3 trillion a year on health care. And it's estimated, depending on the study you look at, that up to a third of that is wasted care. And I think a prime example of this is treating healthy people with statins.
REHMSo from your perspective, Dr. Roberts, when would you prescribe statins?
ROBERTSTo a healthy person?
REHMTo a healthy person whose LDL is at a certain level already stated by the AMA as saying, well, you ought to be careful here.
ROBERTSRight. Well, the only exception I make, pretty much, to putting a healthy person, who doesn't have diabetes or other risk factors, on a statin is the rare disease called familial hypercholesterolemia. And when I was a young doctor many years ago, I worked with Dr. Robert Levy at the NIH, who wrote the seminal paper on this disease. And those people have LDLs in the three to 400 range, and they benefit from statins.
REHMDr. Barbara Roberts, Dr. David Pearle, Sharon Begley -- they're here to answer your questions after a short break.
REHMAnd we're talking in this hour about the use of statins when individuals have high cholesterol rates or lower cholesterol rates. We've got an email here -- and this from a 40-year-old male who says he inherited high cholesterol on his mother's side. He says, "My father died at 50 of heart disease. Both of my grandfathers died of heart disease. My doctor has just prescribed a statin for me because my cholesterol is at 280.
REHM"Everyone I've talked to who's been taking a statin complains of side effects, so I'm very afraid to take it. I don't smoke. I'm very healthy, very active and very health conscious." What to do, Dr. Pearle? And there, we come into the question of what is healthy.
PEARLERight. And I agree with Dr. Roberts on most things. This particular patient, she and I, you know, might disagree. Here would be my take on it: large studies show that the relative benefit of statins in terms of decreasing cardiac outcomes is about the same across the whole risk spectrum. But if your individual risk is very low indeed, that relative risk is meaningless. I mean, if your risk is very low, who cares if there is a 20 percent reduction which is roughly where it is.
PEARLEThe question is, where does this man fall in the risk spectrum? He has an exceptionally bad family history, so he is not the kind of person who is healthy in the sense that he has no risk at all. So we look at a combination of risk factors. He has family history. He doesn't have -- and he has high cholesterol. He does not have diabetes. He does not have high blood pressure. He smoke -- he does not smoke. Sounds like he exercises regularly.
PEARLEHe has good health habits. Where does he fall in the risk spectrum? To me, he would fall high enough in the risk spectrum that I would probably start a statin. But I would also add we have a lot of other newer technologies for trying to predict risk with more scientific precision. Hopefully, someday, he can get a genetic test that will say, you know, despite his family history, he does not have much risk.
PEARLEYou know, his mother's family was in good shape. And I think as time goes on, we're going to have much better ways to predict risk. Today, there are a few other techniques that would help further risk-stratify, that would give additional information over and above family history in the so-called Framingham risk factors.
REHMDr. Roberts, Dr. Pearle says, given this person's history and his current cholesterol level, weighing all of that, he would probably start statins. What would you do?
ROBERTSWell, the first thing I would be to instruct the patient in the Mediterranean diet. We have excellent data from a secondary prevention trial called the Lyon Diet-Heart Study, which randomized over 600 people who had survived a myocardial infarction or a heart attack to either the American Heart Association prudent diet or the Mediterranean diet.
ROBERTSAnd this study lasted almost four years. It lasted 46 months. At the end of that trial, there was not only a 70 percent relative risk reduction in heart attacks, there was a 56 percent reduction in dying of any cause, which is better than any statin trials ever shown.
REHMSo in that Mediterranean diet, you're talking about fish. You're talking about olive oil.
REHMYou're talking about vegetables.
REHMAnd you believe that that can be as effective, if not more so.
ROBERTSIt's actually more effective.
ROBERTSThere's something called the number needed to treat. There's an excellent website, run by Dr. David Newman, called thennt.com, which will give you the number needed to treat to show a benefit. The number needed to treat, to prevent death for the Mediterranean diet is only 30. That's better than any statin trial. And the number needed to treat to prevent...
ROBERTSNo. The number needed to prevent...
REHMIt's all right.
REHMYou opined it.
ROBERTSSo anyway, what I'm saying is the Mediterranean diet outcomes are better than any statin trial.
ROBERTSIt also reduced the risk of cancer by 61 percent...
REHMInteresting. All right.
ROBERTS...which no statin trial has shown. In fact, some statin trials have shown an increased risk of cancer.
REHMLet's go to Herb in Cleveland, Ohio. Good morning to you. Thanks for waiting.
HERBGood morning, Diane. Enjoy your show.
HERBQuick question, I am on a statin. I'm 69 years old. And a couple of years ago, my doctor increased the level to 80 milligrams. I was on -- I think it was just 40 or 20. And I also saw that there was a study, I guess, commissioned by somebody that high levels of Lipitor not only stop but reduce the build-up of wall -- build-up of arterial wall build-up. Are the -- your guests familiar with that? And I'd like for them to comment on it.
REHMAll right. Dr. Pearle.
PEARLESure. In patients who should be on a statin who have risk, what we're trying to do is achieve the appropriate target, and we're going to choose the particular statin and a dose of that statin that gets us to the target. We recognize that a lot of the side effects of statin such as muscle pain are related to dose, so as we go to higher doses, the risk of a side effect increases. Now, on the point can atherosclerosis regress, the data are yes.
PEARLEI mean, there are a lot of studies. Of course, they're smaller because they're more complicated, in which patients do coronary arteriograms, do them serially after a prolonged period of getting the lipids to the specified target that show regression of atherosclerosis in coronary arteries. So there's no guarantee it's going to happen in every patient who achieves target LDL levels, but I believe that happens. I tell my patients it happens.
REHMSharon Begley, can you explain for us exactly how these statins work? What do they do once they get into the body?
BEGLEYThey have a number of mechanisms of action, and I'll certainly say that, you know, the doctor should feel free to jump in here. But basically, they decrease how much cholesterol the liver makes. They also change how its -- how the body absorbs it and how it acts in the body. So the overall effect is that you have less cholesterol which is basically a fat in your bloodstream.
REHMAnd to Fort Lauderdale, Fla. David, does that explain it for you?
DAVIDHow does it stop the liver from producing something?
ROBERTSStatins inhibit an enzyme called HMG-CoA reductase which is an enzyme, very early on in the synthetic pathway, our body uses to make cholesterol. The synthetic pathway is like a factory assembly line. And there's something like 26 steps in the process of making cholesterol, and an enzyme critical in an early step is inhibited by statins.
DAVIDAnd is that the -- is that enzyme specific to creating cholesterol?
PEARLEIt -- yes. It's ironic in some ways, and it shows you how complicated research is and why it has to be wide-ranging, that the most important cardiac -- class of cardiac drugs we have work by blocking an enzyme in the liver.
REHMAll right. And thanks for calling, David. We have a comment from julieann on our website, who says, "Many people now have no choice and must take statins in order to qualify for so-called enhanced health insurance. Refusal to take statins means you pay much higher co-pays, higher deductibles. Shouldn't these studies prompt to change in these policies?" What do you think, Dr. Roberts?
ROBERTSWell, again, I want to get back to the point of primary prevention because that's apparently what -- at least part of what this caller-in is talking about. In people taking statins for primary prevention, the risk of developing diabetes mellitus is actually greater than the risk in reducing stroke, for example.
ROBERTSAnd that number needed to treat -- that I was trying to remember before and was having a senior moment is that you need to treat -- to prevent death, 50 people with the Mediterranean diet as opposed to 83 people with statins. So I think that this is another indication of Big Pharma's influence on guidelines and on how medicine is practiced in this country, which I think is very pernicious.
REHMSharon Begley, can you weigh in on that? Is the pharmaceutical industry promoting the use of statins by neglecting to point out the seriousness involved? Any alternative methods that could be used?
BEGLEYWell, they sold about $15 billion worth of statins in the United States. The last year I have was 2009. I think we'd be safe in thinking that that number has increased in the last few years. I don't want to, you know, impute any nefarious motives to the pharmaceutical companies. They are publicly held companies. They're responsible to their shareholders. They're supposed to make money. They're supposed to get a return on their research investment.
BEGLEYBut, you, of course, only have to look in a magazine and see the ads or watch TV and see the commercials to see how strongly statins are pushed. But, again, I don't think there's any great conspiracy here. But the caller's -- the question was very interesting because a lot of employer-sponsored health insurance plans now do what she was asking, namely they have set a target cholesterol level for employees for the health insurance plans participants. And if you don't make that target, you are penalized financially.
REHMDid you know that, Dr. Pearle?
PEARLENo. This is total news to me. And I...
REHMThat's news to you.
PEARLEIt sounds awful. I mean, for one thing, many patients don't tolerate statins. Dr. Roberts talked about her husband. I could talk about my father who don't -- did not tolerate statins because of side effects. But then this very complicated argument of low risk -- patient who falls into a very low-risk group is not going to benefit from a statin and is going to experience the side effects. So this needs to be individualized and how it could be a policy is sort of beyond me.
REHMOn our website, we have a risk assessment tool that listeners can use to calculate their 10-year risk for having a heart attack. It was created by the National Cholesterol Education Program. Have you seen that risk assessment, Dr. Roberts?
ROBERTSYes. And there are various ways you can assess absolute risks. There's the Framingham Risk Score. There's the Reynolds Risk Score. But, you know, it turns out that, particularly, if you look at total cholesterol, that's not a terribly strong risk factor. The strongest risk factor of all is age, and you can't modify your age. You can lie about your age, but that doesn't change it, OK? So the strongest risk factor is age. Family history is a strong risk factor. You can't modify that either.
REHMDr. Barbara Roberts, and you're listening to "The Diane Rehm Show." Let's go to Flint, Mich. Good morning, Matthew. You're on the air.
MATTHEWHi, Diane. Hi to your panel there. I'm a 50-year old, have all the high risk factors: family (word?) left, right and center, around about the same age as I am now, high LDL, low HDL, high triglycerides. I've done Lipitor, tried Crestor. But when I was on the med, (unintelligible) thinking, memory loss, dizziness, and my (word?) seemed to be off a little bit. So I took myself off it -- haven't told my doc yet.
MATTHEWI'm quite happy to hear your panel's -- the ladies anyway back me up on this one. I've started high (unintelligible) oil, low dose aspirin, fish oils, Mediterranean...
REHMYeah. What do you think about that, Dr. Roberts?
ROBERTSI think it's an excellent step. As I said, we -- at the Women's Cardiac Center -- and we see a lot of men also -- the first thing we do is hand out menus, seven days breakfast, lunch and dinner of a seafood vegetarian diet. The Mediterranean diet is a plant-based diet, lots of colorful fruits and vegetables, whole grains. Olive oil is the main source of fat calories.
REHMAll right. And, finally, to Jeddah, Saudi Arabia. Good morning, Kastir. (sp?)
KASTIRYes. Hi, Diane. I really love your show, and I will...
KASTIR...always really enjoy it.
KASTIRAnd my question is also very similar to the previous -- actually caller that, do we have any high (unintelligible) evidence that suggests the effect of vitamin E in lowering cholesterol?
ROBERTSNot that I know of.
PEARLEWe do not. Let me just reemphasize Dr. Roberts' point is there many things you can do to lower your LDL besides statins. And optimal weight, regular exercise, the appropriate diet -- the Mediterranean one is a terrific one -- are really important.
PEARLEThere are large studies on vitamin E that were negative in terms of benefit.
REHMI see. OK. But here is the question, Dr. Pearle. Would you say to a patient who came in with no sign of heart attack in his or her -- their future but with a high level of LDL -- would you say to that person there are lots of things you can do besides taking statins, or would you say, I think I better I put you on statins?
PEARLEWell, I mean, that -- what you said first is clearly where we start. You want to -- I would emphasize healthy -- heart healthy habits, which we recommend for the whole population.
REHMSure. Of course.
PEARLEThey have many other benefits. Then the next step, though, is, what risk does this patient fall into, OK?
PEARLEThey don't have conventional -- if there are no conventional risk factors...
REHMBut the cholesterol...
PEARLE...a very high cholesterol. I'd probably stop there, but most patients are going to -- if they have a high cholesterol, that's one risk factor. Most will have something else in their pattern. And I would assess, by conventional risk factor, something like the Framingham Score, which takes into account high blood pressure and exercise.
PEARLEAnd I would add that there are other tests that further risk-stratify like the CT scan for coronary calcification.
REHMOK. And, Dr. Roberts, what would you do in the same situation?
ROBERTSI wanted to get back to the...
REHMYou've got to go quickly. We're almost out of time.
REHMWhat would you do?
ROBERTSTherapeutic lifestyle change is the cornerstone of therapy.
ROBERTSStop being a couch potato, lose weight if you're overweight, don't smoke and eat a Mediterranean diet.
REHMDr. Barbara Roberts, she is director of the Women's Cardiac Center at Miriam Hospital in Rhode Island. Her book, "The Truth About Statins," came out in April of this year. Dr. David Pearle, he's a clinical cardiologist at MedStar Georgetown University Hospital. Sharon Begley, senior health and science correspondent at Reuters. Thank you all so much.
PEARLEThank you, Diane.
REHMAnd thanks for listening. I'm Diane Rehm.
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