Zetia/Vytorin Study: A Perspective

You may have heard the considerable debate regarding the cholesterol-lowering medication, Zetia. Unlike statins which affect your cholesterol production, this drug blocks the absorption of both dietary and biliary (liver-produced) cholesterol into the blood stream. The drug is intended to provide individuals who cannot reduce LDL cholesterol using diet and exercise with an alternative to high dosages of statin medications. It also was developed for those who simply cannot tolerate statins.

In a recent controversial study reported in the New England Journal of Medicine, the effects of taking Zetia and the statin, Zocor, combined (together known as the drug Vytorin) was compared to the effects of taking Zocor only.

Here are results:

The group taking the two drugs experienced an LDL cholesterol decline that was 27% greater than the Zocor-only group.

Despite the increased lowering of LDL cholesterol in the group that received both medications, both groups saw arterial plaque build at rate that was similar (although those on the combination drug saw a somewhat larger, but not statistically significant, increase).

This finding is at odds with our traditional understanding of the favorable relationship between lower LDL cholesterol and atherosclerosis.

The trial, however, did not directly address whether lowering of LDL cholesterol with the combination drug reduces heart attacks, strokes and other cardiovascular “events.” The combination drug may or may not provide an additional benefit.

So how is the medical community responding?

An editorial in the New England Journal of Medicine observes that “it seems prudent to encourage patients whose LDL cholesterol levels remain elevated despite treatment with an optimal dose of a statin to redouble their efforts at dietary control and regular exercise,” leaving Zetia for special situations. Yet, well trained, qualified doctors continue to prescribe the combination drug more broadly, believing that a single study does not unseat established wisdom.

The human body is profoundly complex, and we simply do not know with certainty how any particular approach will affect our long term health and longevity. We can only play the odds as we know them today. This requires that each of us take an educated approach to our health. Kardea aims to enable the members of its community to make more informed decisions about cholesterol management and natural nutrition.

The Cholesterol "Pill" & Health Policy

Over the past few days, the media has meted out criticisms of Big Pharma and their cholesterol medications. Certainly, some of it is well deserved. Some, however, confuses the issues and does not consider some fundamental issues related to health policy.

A Bit of Background

Statins and other cholesterol medications represent a critical piece of Pharma's profits. Worldwide, cholesterol meds represent the single largest class of drugs sold--exceeding $25 billion per year.

Why so much?

These medications do work to reduce LDL (bad) cholesterol, and the relationship between LDL cholesterol, heart disease and stroke has been well study and confirmed.

Then there is the magnitude of the issue. Combined, cardiovascular diseases are the primary causes of death and morbidity in the United States.

But, these medication do not "heal". Stop taking these medications, and your LDL cholesterol will rise--all other things being equal. Users of cholesterol medications thus may find themselves on these drugs for decades.

Overall, couple the huge population at risk of cardiovascular disease with the length of time that these medications are potential used, and a huge market is created.

An Oversold Solution?

Cholesterol medications have been oversold and hyped in their ability to remedy heart issues.

Managing cholesterol can improve the cardiovascular system, but it is not and cannot be a guarantee of heart health. Cholesterol also can be managed by means other than medications--nutrition, weight control and exercise. Nutritional approaches that combine nutrients that actively and positively influence blood lipids ---Omega-3 & monounsaturated fatty acids in lieu of saturated fats, plant sterols, soluble fiber, niacin---can achieve results equivalent to many of medications, particularly for the borderline line high cholesterol types like me. This view is widely endorsed in the medical community including the American Heart Association and the American College of Cardiologists.

Certainly, this does not mean that these drugs are without value. For many, the lifestyle and nutritional approaches are not adequate. Medications is required, and for those at high short term risk, they may be essential. Yet, theses meds should complement the therapeutic lifestyles. The approaches should be integrated and the medications should not be the first line of therapeuty.

Moreover, these medications are most effective in affecting only a component of cholesterol---lowering LDL cholesterol. There are other aspects of blood lipids that are important for heart health---the level of HDLs, the ratio of total cholesterol to HDLs, the size of the LDL particle--to name just a few.

Even in regard to LDL cholesterol, a single medication may not achieve heart risk adjusted targets (to calculate your risk-adjusted ldl targets, go to http://www.kardeanutrition.com/cholesterol/ldl_calculator.aspx ). The pharmaceutical solution is to identify other drugs to be taken with the existing medications.

No doubt, new drugs are coming to market or are in development that work with existing medications to favorably affect blood lipid levels. So, you can look forward to taking more medications! Today, we find ourselves with many people taking many drugs, and overall, we are only dimly aware of their interactions and long term afffects on health.

Drivers of a Healthcare Imbalance

From a health policy perspective, we need to give careful thought to what is going.

One issue is that we allow Big Pharma to spend hundreds of millions dollars per year promoting these medications. At whose expense? Well for one, the consumer advertising campaigns dwarf the public health education campaigns that advance nutritional and lifestyle alternatives. We all would be well served if the consumer received more balance input.

A few policy alternatives could be considered. We could require the pharmaceutical companies to contribute an equivalent amount of advertising money to lifestyle and nutrition public health education. This would not be unlike the tobacco companies funding of smoking cessation programs. Alternatively, we could require those media outlets that air these promotion to donate airtime to publilc health education.

Consumer behavior and incentives also are at issue. The advertising ---this unnecessary hype- works in large part because many consumers want to believe that a single pill will eliminate the risk of heart disease--regardless of what they eat, how much they weigh or how much exercise they get. Intellectually, not many of us would ever concede that we believe in the power of the single pill. Practically, the single pill gives us comfort when we fail to live heart healthy lifestyles.

At least for the well-insured consumer, it also may be cheaper, both in terms of time and money, to pursue the pharmaceutical approach than to embrace the alternatives.

Presidential candidates from both parties are discussing fundamental changes in our health care system. Special interest, including Big Pharma, can be expected to mold this system to their benefit. As citizen, we will be best served by making sure that real public health is advanced. Make your voice heard in this debate!

"Cholesterol Drug Bombs"-New York Times Editorial Misses Opportunity

Yesterday, the New York Times editorial board wrote "there have long been suspicions, but it was still very disturbing to learn this week that a heavily promoted cholesterol-lowering drug had flunked a clinical trial of its effectiveness in reducing fatty deposits in arteries....The drug, Zetia, and a combination pill that contains it, Vytorin...generated more than $5 billion in sales last year."

You probably know the ads for Vytorin. They have run on T.V., in magazines and on-line. They certainly are clever, creative and very expensive. According to Nielsen Monitor-Plus, in 2006 the companies spent $136.3 million to advertise Vytorin and $115 million from January to October of 2007.

Vytorin combines Zocor, a statin produced by Merck (and also marketed by generic drug manufactures and sold at lower prices) with the Schering-Plough's Zetia. Statins work by reducing the production of cholesterol in the liver. Zetia works to reduce the absorption of dietary and liver-produced cholesterol from the intestines into the blood stream.

The study compared the effects of treating patients with Vytorin, the combination drug, with a statin alone. The patients all had abnormally high LDL cholesterol. In the study, LDL cholesterol was reduced more significantly by Vytorin than with the statin alone. These results are consistent with the results of a number of other studies.


It also was hypothesized that the added cholesterol-lowering effect of Vytorin would lead to a more significant reduction of arterial plaque growth. This relationship did not hold. The lower cholesterol achieved by the Vytorin did not yield a reduction in plaque build-up as compared to the statin only. In fact, the Vytorin group was found to have a more rapid development of plaque than the statin-only group.

The Times reports that these companies had been “cynically sitting on the results for more than a year” while spending hundreds of millions of dollars to convince consumers that the Vytorin is a preferred cholesterol drug. This certainly is a very legitimate criticism.

The Times continued that "the findings also raise doubts about the current belief that lowering cholesterol is the key to cardiovascular health. The study showed that Vytorin reduced bad cholesterol significantly more than Zocor alone. The problem was that it failed to reduce the formation of plaque."


And here is perhaps were the Times should have been somewhat more careful. This study now represents a single set of data among a sea of data that concludes lower LDL cholesterol lowers the risks of heart attacks and strokes. Numerous studies also indicate that LDL cholesterol above 100mg/dl will lead to the development of arterial plaque.

Instead of casting doubt on the general wisdom of cholesterol management, the Times would have served the public well by offseting the barrage of pharmaceutical advertising and reinforce the well-documented science regarding natural alternatives to cholesterol management. An extensive NIH report (http://www.nhlbi.nih.gov/health/public/heart/chol/chol_tlc.htm), for instance, concludes that the "amount of LDL reduction from Therapeutic Lifestyle Changes compares well with many of the cholesterol-lowering drugs." Among the recommendations are the consumption of certain positive nutrients such as plant sterols, soluble fibers, monounsaturated fats in place of saturated and trans fats, and Omega-3s. Needless to say, weight management and exercise is part of the NIH recommendations.

For more information on natural cholesterol management nutritients: http://www.kardeanutrition.com/cholesterol/program.aspx