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Any Advantages Or Is Livalo Just One More Statin?

When I heard that Livalo was being promoted as the newest statin to market I first wondered why anyone would bother to bring a newer drug to a field of excellent drugs many of which have been around long enough to be available as inexpensive generics.  The primary sales pitch of the Kowa-Lilly reps seems to be that this is “mg. for mg. the most potent statin” available.  By this they mean that per mg. of dosing it lowers LDL cholesterol more than any other statin.  Anyone who understands pharmacology at all immediately recognizes this as meaningless statement.  Every drug has its appropriate dose, and comparing the number of milligrams of one drug to the number of mg. of another drug is just silly.  In essentially every class of drugs each medication has its own appropriate dose and comparing the dose in mg of one drug to another, and saying that the drug with the lower mg dose is more potent is just ridiculous.

Livalo has a number of things going against it and at this point I cannot think of a single reason I would prescribe it unless someone can show it to have unique benefits as compared to more established statins.  Here are my concerns and reasoning:

  • No Better at Lowering LDL: Livalo is promoted by its manufacturer to be equally effective at lowering LDL cholesterol at its medium and highest doses to atorvastatin (Lipitor) and Simvastatin (Zocor).  Average LDL reductions as follows:
    • Livalo 2 mg = 38 – 39% reduction
    • Atorvastatin 10 mg = 38% reduction
    • Simvastatin 20 mg = 35% reduction
    • Livalo 4 mg = 44-45% reduction
    • Atorvastatin 20 mg = 44% reduction
    • Simvastatin 40 mg = 43% reduction
    • Atovastatin 40 and 80 mg dosing not compared to Livalo.
  • No Data for Cardiovascular Outcomes:  Livalo has no data for primary efficacy at reducing cardiovascular morbidity or mortality.  This type of data is well established for simvastatin and atorvastatin.  This is a big deal.  Why use a drug with no reason to expect superior efficacy that lacks data to even be confident it has any efficacy at the real desired outcome.
  •  High Price for Many Years:  Livalo has just been released to market.  It is priced at drugstore.com at 115.99/ 30 tablets.  This compares to simvastatin 20  at $5.90/ 30 tablets  at Costco (no Livalo price online at Costco, likely because there is so little market demand).  Generic Lipitor (atorvastatin) will become available as a generic late this year, and is currently available at Costco at $165.70/ 30 tablets.  All told the generic statins are appropriate for the vast majority of patients.
  • Safety Data Pending:  Why use a drug with no apparent advantages immediately after it comes to market.  All of us remember the fiascos of many newly released drugs when they became available to the mass market and serious problems came to light.  (Think Ketek and Vioxx)

Livalo seems to have a side effects profile very similar to the currently available statins.  If there is a lower incidence of myalgias and myositis there may turn out to be a niche role for Livalo, but at this time I’ll wait to see a lot larger experience than the studies presented so far.

Summary on Livalo:  A simply Ho-Hum new drug that I plan to forget the name of as soon as I finish this post.  Stick with either a good generic like simvastatin.  If you need a branded drug use one with more post-market experience and the promise of being available as a generic very soon like Lipitor.  Overall the Simvastatin vs Lipitor debate leans towards simvastatin until Lipitor becomes generic.  Then I anticipate atorvastatin to be the stain of choice for most patients.  For the patient who has mild to moderate myalgias on either of these two drugs, consider a very low dose of pravastatin or even red yeast rice.

Lipid Type

HDL, LDL, non-HDL Triglycerides – Understand the Jargon

Physicians talk of the lipid profile, or lipid type while most patients want to know about their cholesterol.  We really are on the same team, looking for the same goals of reducing the risk of heart and artery disease caused by abnormally levels of the types of lipids that lead to atherosclerosis.  We just have different words we use.  The jargon physicians use can be confusion, and lipid type is a good example.  First some definitions:

Lipid: really another word for fat.  A lipid is a substance that disolves in alchohol but not in water.  Examples of lipids are wax, oil and other fats.

Cholesterol: a specific lipid that is used for many purposes in the body including cell membranes, hormones, vitamin D production and bile production.  It consists of a sterol carbohydrate ring with specific side chains.

Lipoprotein: a particle manufactured in the liver that consists of lipids and protein that circulates in the bloodstream.

Triglyceride: molecule made up of a three carbon molecule glycerin with three long carbon chain fatty acids attached, i.e. “tri” for three + glyceride. Practically these are the fatty particles in the blood stream that did not get packaged into lipoproteins in the first pass of the blood from the gut through the liver.

HDL cholesterol: (High density lipoprotein) Think good cholesterol here.  The HDL  lipoprotein particle consists of more proteins which are more dense, and less lipids which are less dense, so the lipoprotein is high in density.  There are several subsets of HDL, but in general a high HDL level is good.  HDL cholesterol functions in part to remove cholesterol from places it does not belong and return it to the liver to be repackaged and better used.

LDL cholesterol: (Low density lipoprotein) Think bad cholesterol here.  A lipoprotein that is higher in lipid and lower in protein making it low density.  In general high levels of LDL cholesterol are not good, as they increase the risk of atherosclerosis and heart disease.  LDL cholesterol is the primary vehicle for carrying cholesterol in the blood stream.  When present in large amounts cholesterol is often put where it can cause harm, like on the lining of blood vessels.

CRP: (C-reactive protein or hsCPR for highly sensitive CRP) is a marker of inflammation, and is used sometimes to assess risk of heart disease when the cardiovascular risk based on the rest of the lipid measurements and the other risk factors do not lead to a clear decision on lipid management.

Non-HDL cholesterol: This is simply calculated by subtracting the HDL cholesterol level from the total cholesterol level.  non-HCL cholesterol is a secondary target for treating lipids, after the LDL goal is met.

Direct LDL: usually the LDL level is calculated using the formula:

Total Cholesterol – HDL cholesterol – Triglycerides/5 = LDL cholesterol

This formula is quite accurate except when the triglyceride level is over 400-500.  High triglyceride levels make this calculation less accurate, so in those cases a more expensive test is used to measure the LDL cholesterol directly.

Physicians use these numbers along with a patients other risk factors to decide on whether to treat them with medication for abnormal lipid measurements.  In general the more risk factors for heart disease a patient has the more likely they are to warrant medication treatment.

The risk factors recommended by the National Institute of Health (through the NHBLI)  for this decision making include:

Table 3. Major Risk Factors (Exclusive of LDL Cholesterol) That Modify LDL Goals*

- Cigarette smoking

- Hypertension (BP ³140/90 mmHg or on antihypertensive medication)

-Low HDL cholesterol (<40 mg/dL)†

-Family history of premature CHD (CHD in male first degree relative <55 years; CHD in female first degree relative <65 years)

-Age (men ³45 years; women ³55 years)*

* In ATP III, diabetes is regarded as a CHD risk equivalent.

HDL cholesterol ³60

(table from the NIH site)

The levels of cholesterol are broken down into categories:

Table 2. ATP III Classification of LDL, Total, and HDL Cholesterol (mg/dL)

LDL Cholesterol

<100                                       Optimal

100-129                                 Near optimal/above optimal

130-159                                 Borderline high

160-189                                 High

>190                                       Very high

Total Cholesterol

<200                                Desirable

200-239                          Borderline high

³240                                  High

HDL Cholesterol

<40                                    Low

>60                                     High

(table from the NIH site)

The recommendations for goal LDL cholesterol are as follows:

Three Categories of Risk that Modify LDL Cholesterol Goals

Risk Category LDL Goal (mg/dL)

 

CHD and CHD risk equivalents           <100

Multiple (2+) risk factors*                   <130

Zero to one risk factor                           <160

* Risk factors that modify the LDL goal are listed in Table 3

(from the NIH site)

Using these recommendations a woman age 67 who does not smoke, has a BP < 140/90 on no blood pressure medication, has an HDL cholesterol of 38, and has no coronary heart disease in her mother, father, or siblings would have 2 risk factors (age plus low HDL cholesterol) making her goal LDL <130.

Similarly a man age 40 who smokes, is on BP medication, and whose father had his first heart attack at age 50 with an HDL of 33 would have three risk factors (smoking, blood pressure and family history)  so his goal LDL cholesterol would be <130 unless his Framingham calculated risk of developing Coronary disease in the next 10 years is >20%.

Here is a link to the calculator provided by the NIH  to calculate Framingham Risk:

Framingham Risk Calculator

Using this calculator the 10 year risk of the man above would be 22% if his current systolic BP was 130 on medication, so he falls into the CHD equivalent category and has a goal of <100 for LDL cholesterol.

Treating LDL cholesterol is usually pretty straightforward.  We try to get patients to eat a diet low in total fat and saturated fat (primarily animal fat) to avoid trans fatty acids, and to lose weight.  If this is not adequate we usually add a medication in the statin family.  Many generic statins are available and can keep costs of treatment fairly low, and most patients tolerate statins well.  Some patients do not and red yeast rice is sometimes tolerated by those patients.  It has a statin-like effect.  Statins can lower LDL cholesterol by 25-55% in most patients.  If statins are not tolerated, or if you are a woman who may become pregnant (absolute contraindication to statins) then other medications are sometimes used.

Treating low HDL cholesterol is more difficult, and often slow release niacin is used for this purpose, but it is sometimes difficult to tolerate because of flushing and itching side effects.

Treating triglycerides is important if they are extremely high.  Levels >500 can put you at risk for pancreatitis, and need to be treated.  Levels between 150 and 500 are suboptimal, and are sometimes treated.

In general the goals for non-HCL cholesterol are the LDL goals + 30.

Hopefully this has been helpful in understanding your lipid profile.  If you have suggestions for improvement, or other comments, please leave them in the comments section below.

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Red Yeast Rice lowers LDL as well as Pravastatin

Pravastatin is the lowest potency statin that is widely used in the US to lower LDL cholesterol.  It is often tolerated even in patients where other statins cause muscle pain.  Red Yeast Rice extract is a well tolerated supplement that has been touted to lower LDL cholesterol.  A study published in the Jan 15th issue of Am. Journal of Cardiology compares 2400 mg twice daily Red Yeast Rice extract with 20 mg twice daily pravastatin in a small group of patients who did not tolerate more potent statins.  It turns out that both regimens are equally well tolerated and equally effective.  Both reduce LDL levels by about 30%, and both are not tolerated by <10% of patients in this difficult population where another statin was already not tolerated.