Cholesterol-Lowering Drugs: What You Need to Know

WebMD Live Events Transcript

When you're trying to lower yourcholesterol, you know that eating right is the first step. But what is the role ofdrugsin your fight to lowercholesterol levels? We asked Michael Chesner, MD, when he joined us on Nov. 3, 2004.

The opinions expressed herein are the guests' alone and have not been reviewed by a WebMD physician. If you have questions about your health, you should consult your personal physician. This event is meant for informational purposes only.

This event was brought to you by Reliant Pharmaceuticals. Reliant Pharmaceuticals is the manufacturer of Lescol XL, a drug approved to reduce total elevated cholesterol.

MEMBER QUESTION:
I don't want to take medicine for my cholesterol. It was 245 and my doc still wants me on it. I gowalkingevery day and watch what I eat. What else can I do?

CHESNER:
There are many ways to lower cholesterol without resorting to medications. I should add, however, that in a majority of cases elevated cholesterol can be treated both safely and effectively with appropriate medications by a health care provider. I too have many patients who are uncomfortable with the concept of taking medications and am therefore forced to help them find alternative treatments forlowering cholesterol. Several methods exist to assist with that:

• Dietary managementis an important method of lowering cholesterol, reducing saturated fat in thediet,减少乳制品,红肉,certain oils, such as palm and coconut, are helpful adjuncts to lowering cholesterol.
• Exercisehas also been shown to be beneficial at lowering cholesterol levels as well as raising the level ofHDL, which we know to be the good cholesterol in the bloodstream.
• Some patients treat themselves with a product from a health food store known as红曲米and feel they are taking a more healthful treatment for their cholesterol. What they don't realize, however, is that this is in fact similar to the statin class of cholesterol-lowering drugs and is therefore subject to the same potential side effects as that particular class of drug, without the benefit of FDA monitoring.
• Metamucil,one to three times daily, has been shown in a study published several years ago in theJournal of the American Medical Association, to reduce total cholesterol by approximately 17%. Some patients are more comfortable with this agent than with medications.

I should repeat, however, that in a majority of cases, patients do benefit from one of the available medications for lowering cholesterol and that they can be used safely and effectively.

"Most cholesterol-lowering medications are better able to decrease LDL and at present the options for raising HDL are somewhat more limited."

MODERATOR:
This questioner mentioned a level of "245," but that's a combined number, I'm guessing. Can you go into more detail about the different types of cholesterol? Not all cholesterol is bad, right?

CHESNER:
There are different substances in the bloodstream that make up the total cholesterol level. In general, theLDL cholesterolis the more dangerous and the more important number to lower, while the HDL is the good cholesterol, which we want to be as high as possible.

A little mnemonic device I teach my patients to help them remember is: the HDL is happy when it's high, while the LDL we want to be low, for the letter L. That helps patients remember the difference between them.

It is interesting to note that most cholesterol-lowering medications are better able to decrease LDL and at present the options for raising HDL are somewhat more limited. I expect over the next five years more medications to be available to raise the HDL, which would be as beneficial if not more beneficial, than lowering LDL, as our present medications are best able to do.

MEMBER QUESTION:
Should I be worried about takingCrestorbased on the recent warnings about its safety?

CHESNER:
Statins适合该类称为HMG CO-A inductasehibitors. These drugs are the class most often used today for cholesterol reduction. In fact, they make up the largest dollar value of medications prescribed in the United States today. Currently in the United States over 17 million people are currently using statins, and another 15 to 20 million should be on them, based on their risks and current cholesterol levels.

They are, by and large, safe and highly effective at lowering total cholesterol andLDL cholesterol. They also lowertriglyceridesand modestly raise HDL, the good cholesterol, in many patients. They have been used since the 1980s and have been shown to preventheart attacks,strokes, and death in millions of people, based on numerous well-published studies. As a class, they are by and large very well tolerated, and have been associated with few, but very well publicized, side effects in a small minority of patients.

For those who are unaware of which drugs are in this class, they include Privation,Lipitor,Zocor,Lescol,Mevacor, and Crestor. There had been one other member of the class, known as Baycol, which was removed from the market in the year 2001 due to a higher than expected frequency of cases of muscle breakdown that had been noted with Baycol.

Crestor is a very powerful statin that has been shown to reduceLDL cholesterolbetter than any of the other statins currently available when compared milligram for milligram. However, at higher dosages, it has been shown to have a slightly higher than expected amount of muscle inflammation associated with it, and therefore patients at higher dosages, such as Crestor 40 milligrams per day, should be followed closely with regard to measurement of their CPK levels.

In general the side effects of the statin class are noted in 1% or less of patients and can include:

• Nausea
• GI upset
• Malaise
• Fever
• Elevation ofliver tests
• Muscle aches ormuscle cramps

Sometimes the muscle aches are associated with elevated levels of a muscle enzyme known as CPK, or creatine kinase, that can be measured in the bloodstream. Most physicians will monitor blood levels of this enzyme and stop the medication if the level of the muscle enzyme exceeds a certain number.

In the most severe of cases a large amount of muscle breakdown from a statin can cause the kidneys to be overwhelmed from trying to clear the products of muscle breakdown and can causekidney failureand even death. This has been seen with all of the statins, except Lescol, during the last 15 years of statin use. It is, however, exceedingly rare, occurring in less than one in 10,000 cases.

Some of the factors that can increase the chances of this severe muscle breakdown occurring during statin use include when a patient takes certain other medications together with the statin class, such asfibrates,某些抗生素,如erythromycin,Biaxin, Cyclosporin, a drug used in transplant patients, as well as certainantidepressantsand medications given for the treatment ofHIV.

"Our experience over the last 20 years with the statins indicates that their benefit, in an overwhelming majority of patients, outweighs the risk."

MEMBER QUESTION:
Do you have any special considerations/suggestions for people who are already taking other medications?

CHESNER:
Certain studies have shown that several options are available to patients who develop problems with statins or are afraid of the risks of combining statins with certain other medications, as I just mentioned. Privation and Lescol, due to their different method of metabolism, are considered safer statins when combined with the classes of drugs that I mentioned above and can be used concomitantly with them.

Alternatively, drug dosages of statins can be reduced as a means of trying to offset and prevent side effects when on concurrent other medications. At times, the statins should be stopped if a patient was to go on a brief course of a medication such as Biaxin, so that the Biaxin and the statin are not to be taken at the same time.

MEMBER QUESTION:
Is it safe to be on this kind of drug for long?

CHESNER:
There is probably no other class of drug that has been studied as extensively and as long as the statins have since their introduction with Mevacor in the early 1980s. Certainly looking back over the last 20 years of our experience with this class of drug, no increase in mortality in well-monitored patients has been noted. In fact, as a class, they reduce the risks of death,stroke, andheart attackby between 25% and 35% across the board. Each one of them is used safely in an overwhelming majority of the patients who take them.

As with all medications, nothing should be taken unless the benefit outweighs the risk. Certainly, given the fact thatatherosclerotic heart disease, orhardening of the arteries, is the No. 1 killer of people in the United States, any method that we have to reduce that risk by 35% should be very, very widely used, if possible.

Of course, in those patients in whom the risks of medication outweigh the benefits, alternative courses of action should be sought. However, our experience over the last 20 years with the statins indicates that their benefit, in an overwhelming majority of patients, outweighs the risk.

MEMBER QUESTION:
Would you recommendfolic acid,fish oiland B-12 to lower cholesterol?

CHESNER:
Folic acid has a different benefit from a cardiovascular standpoint that has been shown in certain studies to be of benefit. The main purpose of folic acid and the Bvitaminsis to lower the level of homocystine in the bloodstream. Elevated levels of homocystine are associated with an increased risk of atherosclerosis and studies have shown that patients with elevated homocystine who undergoballoon angioplastyhave better results when their homocystine levels are lowered.

Given the benign nature of folate replacement, homocystine is a substance that I routinely measure on my patients and recommend folic acid replacement in those in whom the homocystine level is too high.

Fish oil has some benefit at cholesterol reduction; however, in some studies, the amount of fish oil that was required to reduce the cholesterol level was so high that patients literally smelled like a fish market and was socially not worth the price that people paid for their "natural" method of reduction.

MEMBER QUESTION:
My doctor told me that I have relatively low bad cholesterol levels, but still wants to give me a statin drug. Is this normal?

CHESNER:
I don't know the specific facts of your case. I can say the following statements in general, however: The benefits of the statins are not just that they lower cholesterol levels, but they also seem to have beneficial effects above and beyond simply lowering cholesterol. Arterial blockages can rupture and induce strokes andheart attacks. The statins are all able to stabilize these plaques. Patients who are on statins also benefit from other beneficial factors on the bloodstream. These include a blood-thinning property that makes strokes andheart attacksless likely to occur.

If a patient has a cardiovascular event, such as astrokeorheart攻击,即使他们的胆固醇水平not fit into [high guidelines] I will often recommend their cholesterol level be reduced even more, because their cholesterol level was obviously for them too high, despite the fact that as compared with others, the cholesterol doesn't fit into a high category.

"Cholesterol has some useful purpose in the human body, in that it acts as the sheath around nerve cells. We have not yet seen an LDL number, however, where lowering cholesterol below that level has shown to be detrimental."

MEMBER QUESTION:
How low is too low for cholesterol? Could a statin like Crestor make it too low?

CHESNER:
We don't yet know how low is too low, nor do we yet know how low to drive the cholesterol to. Cholesterol has some useful purpose in thehuman body, in that it acts as the sheath around nerve cells. We have not yet seen an LDL number, however, where lowering cholesterol below that level has shown to be detrimental.

As of this current date, there is evidence that in patients with established atheroscleroticheart diseasethat LDL levels less than 70 may be more beneficial than LDL levels under 100, which had for several years been the recommended goal.

MEMBER QUESTION:
I have been trying for about eight years to lower my cholesterol bydietingand watching the fat intake of my food. I was never able to lower it until I started takingZetia. I found out that it is the only cholesterol-lowering medication that does not work on theliver; it works through theintestines. For people who may have liver problems, why is Zetia the only one that works in the intestines? Is there a generic brand for Zetia? If not when will there be?

CHESNER:
Zetia, also known generically atezetimibe, is the first of a new class of drugs to lower cholesterol that works as cholesterol absorption inhibitors in the intestine. It has only been available for a little over one year at this point, and is therefore not likely to be available generically for several years.

It is a drug that is taken orally and blocks the absorption of cholesterol within the intestine, and is able to lower cholesterol modestly when taken on its own, and also can be used together with a statin thereby providing patients with a dual mechanism of reduction of cholesterol. I often use it together with a statin to further reduce LDL in those patients who are not yet at their goal cholesterol, despite being on a statin.

I also sometimes use it by itself in those patients who are either afraid of a statin or were intolerant of statins in the past.

The side effect profile of ezetimibe is essentially similar to placebo, based on the medical literature; however, some patients will complain of abdominal discomfort. In the overwhelming majority of patients, however, no side effects are noted.

As compared with a statin that can lower LDL levels 35% or more when used at starting dosages, Ezetimibe lowers cholesterol more modestly, approximately 15% to 20%, when used on its own.

MEMBER QUESTION:
Are there certain people who should be more concerned about lowering cholesterol?

CHESNER:
Since the mid-1980s statins have been studied in many, many patients in both primary and secondarypreventionstudies. Primary prevention studies refer to studies in which the statins were used to prevent strokes, heart attacks, and death, in people who did not yet have those events occur, while secondary prevention studies are studies that demonstrate the benefit of treatment in preventing recurring events in those who have already suffered astrokeor heart attack.

Since by definition someone who has had astrokeor heart attack is at high risk of having a recurrent event, any method or treatment that would reduce that risk should be considered very strongly. The statins have been shown to greatly reduce the risks of recurrent strokes or heart attacks, especially in those patients that are at highest risk, such as people withdiabetes, and those with other manifestations ofcardiovascular disease.

Almost all patients who have had a stroke or heart attack should be on a statin, unless there is a contraindication to treatment. The mathematical risk reduction approaches 40% in some studies.

MEMBER QUESTION:
Do you have any advice to people taking statins about questions to ask their doctors?

CHESNER:
Patients should be well informed about the risks and benefits of any medication they take. Patients that are on statins should make sure that their blood is checked at regular intervals for liver and muscle abnormalities, even if they are asymptomatic. And they should alert any health care provider who gives them another concurrent medication that may interact badly with the statin, so as to minimize the chances of drug/drug interactionsand help them to maintain safe use of their statin.

"Patients on statins should make sure that their blood is checked at regular intervals for liver and muscle abnormalities, even if they are asymptomatic."

MEMBER QUESTION:
Can you talk about combination therapy, taking more than one cholesterol-lowering drug at a time?

CHESNER:
For many patients, a single drug alone is unable to lower cholesterol to goal LDL numbers. For those patients, a combination of treatments must be used. As I mentioned before, I frequently combine Zetia with a statin to further reduce LDL with minimum risk. In some patients, a fibrate needs to be combined with a statin. In those cases, blood tests should be done more frequently, as the statin/fibrate combination in some patients can increase muscle inflammation. At times statins can be used together with resin binders, as well.

I believe that as we learn more about the need to raise HDL and effectively lower LDL andtriglycerides, more and more patients will be on combination therapy.

MODERATOR:
Before we wrap things up for today, do you have any final words for us, Dr. Chesner?

CHESNER:
It is rare that a class of drug be available that is as safe and effective in an overwhelming majority of patients as there is in the case of the statins. Unfortunately, the bad press that a few cases generate often scares people away from taking what could potentially be a lifesaving therapy. People should make informed decisions together with their health care provider before deciding whether to take or not take a medication, given its potential for good in the overwhelming majority of patients.

MODERATOR:
Our thanks to Michael Chesner, MD, for joining us.

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