Ezetimibe Prescribing Fails to Keep Up With Evidence - JAMA

Ezetimibe Prescribing Fails to Keep Up With Evidence     

Mike Mitka, MSJ 

             

JAMA. Published online March 19, 2014. doi:10.1001/jama.2014.2896

          

 

Although physicians like to think they practice evidence-based medicine, that appears to not be the case with prescribing the cardiovascular drug ezetimibe. And some critics say that use of surrogate markers to guide practice rather than clinical outcomes such as occurrence of myocardial infarction, stroke, or death has likely played a role.

 

Ezetimibe is an intestinal cholesterol absorption inhibitor found to reduce low-density lipoprotein cholesterol (LDL-C) levels by about 20% when given alone. It also further reduces LDL-C levels when added to statin therapy, which blocks cholesterol synthesis in the liver by inhibiting HMG-CoA reductase.

 

The Food and Drug Administration approved ezetimibe in 2002 for use in the United States primarily because it lowered LDL-C levels, a surrogate marker for prevention of cardiovascular disease. Whether ezetimibe improved clinically meaningful outcomes remained a question.

 

That question was somewhat answered in January 2008, with the announcement that the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial, sponsored and conducted by industry, found that the addition of ezetimibe failed to reduce atherosclerosis progression compared with simvastatin alone, despite lowering LDL-C levels. Atherosclerosis progression was determined by a change in the intima-media thickness of the walls of the carotid and femoral arteries—yet another surrogate end point (Kastelein JJP et al. N Engl J Med. 2008;358[14]:1431-1443).

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Graphic Jump Location

US and Canadian physicians continue to prescribe ezetimibe even after a study found giving the drug with a statin failed to reduce atherosclerosis progression compared with the statin alone.

 

 

The ENHANCE result prompted some leaders in the cardiology community to question ezetimibe’s place in cardiovascular disease treatment. Harlan Krumholz, MD, professor of medicine and epidemiology and public health at Yale University in New Haven, Connecticut, said the study should change practice. “Although not definitive, [ENHANCE] increases our uncertainty about the clinical value of this novel drug. Without some evidence of improved outcomes associated with its use, ezetimibe should be relegated to a last option for patients who need medication for hypercholesterolemia, and even in these cases, it is reasonable for clinicians and their patients to wait for further information before considering it,” he wrote in NEJM Journal Watch (http://tinyurl.com/pk9xr29).

 

So did the ENHANCE results change practice? In the United States, the answer is “somewhat,” while in Canada, the answer appears to be “no.”

 

In a study published in the American Heart Journal, researchers looked at ezetimibe prescription trends before and after ENHANCE, using data collected from CompuScript in Canada and IMS Health in the United States from January 1, 2002, to December 31, 2009. The researchers found the monthly number of ezetimibe prescriptions per 100 000 population rose from 6 to 1082 in the United States from November 2002 to January 2008 and then declined to 572 per 100 000 population by December 2009, a decrease of 47.1%. In Canada, however, use continuously increased from 2 to 495 per 100 000 from June 2003 (when the drug was approved in Canada) to December 2009 (Lu L et al. Am Heart J. doi:10.1016/j.ahj.2014.01.014 [published online February 27, 2014]).

 

Coauthor Cynthia A. Jackevicius, PharmD, MSc, a professor of pharmacy practice and administration at Western University of Health Sciences in Pomona, California, and an adjunct scientist, Institute for Clinical Evaluative Sciences, in Toronto, said her team was initially surprised by the Canadian results.

 

“Previous findings showed ezetimibe use in Canada experienced a more conservative uptake, so we expected to see a decrease in use in response to the ENHANCE study,” Jackevicius said. “So we looked for different factors, and one is the Canadian lipid guidelines, which specifically said ezetimibe could be added to statins, and that didn’t change after ENHANCE came out.”

A study of ezetimibe use in Saskatchewan, the only Canadian province that lists the drug for open formulary access, even though guidelines say it’s a second-line agent for lowering cholesterol, reflects Jackevicius’s team’s findings. Using data from provincial health administrative databases, the Saskatchewan researchers found that ezetimibe prescriptions were 2.5% of cholesterol-lowering dispensations in 2004 and 8.8% of such dispensations in 2011 (Alsabbagh WM et al. Can J Cardiol. 2014;30[2]:237-243). The authors concluded that allowing unrestricted use of ezetimibe in Saskatchewan may have led to a large number of inappropriate prescriptions, at odds with Canadian clinical guidelines.

 

And although ezetimibe use declined in the United States, its use per 100 000 population is still greater than Canada’s, generating US expenditures of more than $2.2 billion in 2009.

 

Krumholz, one of the coauthors on the study with Jackevicius, remains perplexed as to the continuing popularity of ezetimibe. “The drug continues to defy gravity, and that’s probably a result of really strong marketing and the singular focus on cholesterol numbers,” he said.

 

Krumholz said heart health campaigns urging patients to “know your numbers” and treatment goals based on cholesterol measurements, such as getting asymptomatic individuals’ LDL-C levels below 130 mg/dL, have worked in ezetimibe’s favor at the expense of evidence-based medicine. “Is this the drug that lowers your LDL-C and helps you? We don’t know that,” he said. “The comfort of hitting a target offers little benefit if you don’t know that it is really protecting you.”

 

Although ENHANCE has not derailed ezetimibe prescribing, the newest cholesterol management guidelines just might. The guidelines, issued late last year by the American College of Cardiology and the American Heart Association, abandon the idea of reaching a target level for LDL-C, instead recommending the use of statins to reduce LDL-C levels only for certain types of patients.

Will this change in the guidelines affect ezetimibe prescribing? “It will be interesting to see what the guidelines will do,” Krumholz said.

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Why Women Should Stop Their Cholesterol Lowering Medication - Hyman

Why Women Should Stop Their Cholesterol Lowering Medication

by Dr Mark Hyman   January 19th, 2012

If you are a post-menopausal women with high cholesterol, your doctor will almost certainly recommend cholesterol lowering medication or statins. And it just might kill you. A new study in the Archives of Internal Medicine found that statins increase the risk of getting diabetes by 71 percent in post-menopausal women.

Since diabetes is a major cause of heart disease, this study calls into question current recommendations and guidelines from most professional medical associations and physicians. The recommendation for women to take statins to prevent heart attacks (called primary prevention) may do more harm than good.

Statins have been proven to prevent second heart attacks, but not first heart attacks.

Take it if you already have had one, but beware if your doctor recommends it for you if have never had a heart attack.

This current study adds to an increasing body of literature questioning the benefits of statins, while highlighting their potential risks.

New Study Shows 48 Percent Risk of Diabetes in Women Who Take Statins

This study examined the data from the large government sponsored study called the Women’s Health Initiative, the same study that disabused us of the idea that Premarin prevented heart attacks in postmenopausal women.

In fact, based on this randomized controlled trial, estrogen replacement therapy, once considered the gold standard of medical care for the prevention of heart disease, was relegated to the trash bin of history joining medicine’s many other fallen heroes including DES, Thalidomide, Vioxx, Avandia, and more.

In this new study researchers reviewed the effect of statin prescriptions in a group of 153,840 women without diabetes and with an average age of 63.2 years. About 7 percent of women reported taking statin medication between 1993 and 1996. Today there are many, many more women taking statin medications, thus many more are at risk from harm from statins.

During the 3-year period of the study, 10,242 new cases were reported – a whopping 71 percent increase in risk from women who didn’t take statins. This association stayed strong at a 48 percent increased risk of getting diabetes, even after taking into account age, race/ethnicity, and weight or body mass index. These increases in disease risk were consistent for all statins on the market.
This effect also occurred in those with and without heart disease. Surprisingly disease risk was worse in thin women. Minority women were also disproportionately affected. The risk of diabetes was 49 percent for white women, 57 percent for Hispanic women, and 78 percent for Asian women.
But in a typical “my mind’s made up, don’t confuse me with the facts” statement by the medical establishment, the researchers said we should not change our guidelines for statin use for the primary prevention of heart disease.

In a large meta-analysis published in the Lancet last year, scientists found that statins increased the risk of diabetes by 9 percent. If current guidelines were followed for those who should take statins, and people actually took them (thank God only 50 percent of prescriptions are ever filled by patients), there would be 3 million more diabetics in America. Oops.

Other studies have recently called into question the belief that high cholesterol levels increase your risk of heart disease as you get older. For those over 85 it turns out having high cholesterol will protect you from dying from a heart attack, and, in fact, from death from any cause.

Low Cholesterol May Kill You

A recent study showed that in healthy older persons, high cholesterol levels were associated with lower non-cardiovascular-related mortality. This is extremely concerning because millions of prescriptions are written every day to lower cholesterol in the older population, yet no association has been found between higher cholesterol and heart disease deaths for those aged 55 to 84; and for those over 85, the association seems to be inverse — higher cholesterol predicts lower risk of death from heart disease.

The pharmaceutical industry, medical associations, and academic researchers whose budgets are provided by grants from the pharmaceutical industry continue to preach the wonders of statins, but studies like these should have us look good and hard at our current practices. Are we doing more harm than good?

Cardiologists recommend putting statins in the water and giving them out at fast food restaurants and having them available over the counter. They believe in driving cholesterol as low as possible. Statin prescriptions are handed out with religious fervor, but do they work to prevent heart attacks and death if you haven’t had a heart attack already?

Bottom line: NO! If you want to learn why this is true, read on.

Statins Don’t Work to Prevent First Heart Attacks

Recently, the Cochrane Group did a review of all the major statin studies by an international group of independent scientists. The review failed to show benefit in using statins to prevent heart attacks and death. In addition, many other studies support this and point out the frequent and significant side effects that come with taking these drugs. (i) If scientists found that drinking two glasses of water in the morning prevented heart attacks, even if the evidence was weak, we would jump on board. Big up side, no down side.

But this is not the case with statins. These drugs frequently cause muscle damage, muscle cramps, muscle weakness, muscle aches, exercise intolerance (ii) (even in the absence of pain and elevated CPK – a muscle enzyme), sexual dysfunction, liver and nerve damage and other problems in 10-15 percent of patients who take them. (iii) They can also cause significant cellular, muscle, and nerve injury as well as cell death in the ABSENCE of symptoms. (iv)

There is no lack of research calling into question the benefits of statins. Unfortunately, that research doesn’t get the benefit of billions of dollars of marketing and advertising that statins do. One big trial was touted as proving statins work to prevent heart attacks, but the devil is in the details.

It was the JUPITER (v) trial that showed that lowering LDL (or bad cholesterol) without a reduction in inflammation (measured by C-reactive protein) didn’t prevent heart attacks or death. (vi) Statins happen to reduce inflammation so the study has been touted as proof of the effectiveness of these medications.

Mind you it wasn’t lowering the cholesterol that helped (which is the intended purpose of statins), but the fact that they lower inflammation. What is ignored by people who use this study to “prove” that statins work is the fact that there are so many better ways to lower inflammation than taking these drugs.

Yet other studies have shown no proven benefit for statins in healthy women (vii) with high cholesterol or in anyone over 69 years old. (viii) Some studies even show that aggressive lowering of cholesterol can cause MORE heart disease. The ENHANCE trial showed that aggressive cholesterol treatment with two medications (Zocor and Zetia) lowered cholesterol much more than one drug alone, but led to more arterial plaque and no fewer heart attacks. (ix)

Other research calls into question our focus on LDL or the bad cholesterol. We focus on it because we have good drugs to lower it, but it may not be the real problem. The real problem is low HDL that is caused by insulin resistance (diabesity).

In fact studies show that if you lower the bad (LDL) cholesterol in people with low HDL (good cholesterol) that is a marker of diabesity – the continuum of obesity, prediabetes and diabetes – there’s no benefit. (x)

Most people simply ignore the fact that 50-75 percent of people who have heart attacks have normal cholesterol. (xi) The Honolulu Heart Study showed older patients with lower cholesterol have higher risks of death than those with higher cholesterol. (xii)

Some patients with multiple risk factors, or who have had previous heart attacks do benefit, but when you look closely the results are underwhelming. It’s all in how you spin the numbers. For high-risk males (those who are overweight and have high blood pressure, diabetes, and/or a family history of heart attacks) and are younger than 69 there is some evidence of benefit, but one hundred men would need to be treated to prevent just one heart attack.

That means that 99/100 men who take the drug receive no benefit. Drug ads say the risk is reduced by 33 percent. Sounds good, but that just means the risk of getting a heart attack goes down from 3 percent to 2 percent.

Despite the extensive data showing that statins are a questionable therapy at best, they are still the number one selling drug in the US. What isn’t so well known is that 75 percent of statin prescriptions are written for people who will receive no proven benefit. The cost of these prescriptions? Over $20 billion a year.

Yet somehow the 2004 National Cholesterol Education Program guidelines expanded the previous guidelines to recommend that even more people without heart disease take statins (from 13 million to 40 million) (xiii) What are we thinking?

Why would respected scientists go against the overwhelming research that statins don’t prevent heart disease in people who haven’t already had a heart attack?

You can find the answer if you follow the money. Eight of the nine experts on the panel who developed these guidelines had financial ties to the drug industry. Thirty-four other non-industry affiliated experts sent a petition to protest the recommendations to the National Institutes of Health saying the evidence was weak.

What Should Women Do?
It is time to push the sacred cow of statins overboard.
But first let me say this. If you have had a heart attack, or have heart disease, the evidence shows they do in fact help protect against a second heart attack, so keep taking them. However, you should be aware that most prescriptions for statins are given to healthy people whose cholesterol is a little high. For these folks the risk clearly outweighs the benefit.

The editorial that accompanies the recent study on women taking cholesterol-lowering medication that I opened this article with was quite clear. Dr. Kirsten Johansen from the University of California, San Francisco said that the increased risk of diabetes in women without heart disease has “important implications for the balance of risk and benefit of statins in the setting of primary prevention in which previous meta-analyses show no benefit on all-cause mortality.”

In plain English, she said that we shouldn’t be using statin drugs for women without heart disease because:

1. The evidence shows they don’t work to prevent heart attacks if you never had one.
2. They significantly increase the risk of diabetes.

Treating risk factors like high cholesterol is misguided. We must treat causes – what we eat, how much we exercise, how we handle stress, our social connections and environmental toxins are all more powerfully linked to creating health and preventing disease than any drug on the market.
Remember what you put at the end of your fork is more powerful than anything you will ever find at the bottom of a pill bottle.

My new book The Blood Sugar Solution, which comes out at the end of February, gives exact details on what you should put at the end of your fork to prevent and reverse diabesity. It provides a comprehensive solution to the health problems facing our nation today.

Now I’d like to hear from you …

What do you think of statins?

Have you taken statins? What has your experience been?

Why do you think the medical establishment prescribes drugs that research shows don’t work?
Please leave your thoughts by adding a comment below – but remember, we can’t offer personal medical advice online, so be sure to limit your comments to those about taking back our health!

To your good health,
Mark Hyman, MD

References:

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(i) Abramson J, Wright JM. Are lipid-lowering guidelines evidence-based? Lancet. 2007 Jan 20;369(9557):168-9

(ii) Sirvent P, Mercier J, Lacampagne A. New insights into mechanisms of statin-associated myotoxicity. Curr Opin Pharmacol. 2008 Jun;8(3):333-8.

(iii) Kuncl RW. Agents and mechanisms of toxic myopathy. Curr Opin Neurol. 2009 Oct;22(5):506-15. PubMed PMID: 19680127.

(iv) Tsivgoulis G, et. al, Presymptomatic Neuromuscular Disorders Disclosed Following Statin Treatment, Arch Intern Med. 2006;166:1519-1524

(v) Mora S, Ridker PM. Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER)–can C-reactive protein be used to target statin therapy in primary prevention? Am J Cardiol. 2006 Jan 16;97(2A):33A-41A.

(vi) Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ; JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008 Nov 20;359(21):2195-207.

(vii)Abramson J, Wright JM. Are lipid-lowering guidelines evidence-based? Lancet. 2007 Jan 20;369(9557):168-9

(viii) IBID

(ix) Brown BG, Taylor AJ Does ENHANCE Diminish Confidence in Lowering LDL or in Ezetimibe? Engl J Med 358:1504, April 3, 2008 Editorial

(x) Barter P, Gotto AM, LaRosa JC, Maroni J, Szarek M, Grundy SM, Kastelein JJ, Bittner V, Fruchart JC; Treating to New Targets Investigators. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med. 2007 Sep 27;357(13):1301-10.

(xi) Hansson GK Inflammation, Atherosclerosis, and Coronary Artery Disease N Engl J Med 352:1685, April 21, 2005

(xii) Schatz IJ, Masaki K, Yano K, Chen R, Rodriguez BL, Curb JD. Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study. Lancet. 2001 Aug 4;358(9279):351-5.

(xiii) http://www.nhlbi.nih.gov/about/ncep/index.htm

About Dr Mark Hyman

MARK HYMAN, MD is dedicated to identifying and addressing the root causes of chronic illness through a groundbreaking whole-systems medicine approach called Functional Medicine. He is a family physician, a four-time New York Times bestselling author, and an international leader in his field. Through his private practice, education efforts, writing, research, and advocacy, he empowers others to stop managing symptoms and start treating the underlying causes of illness, thereby tackling our chronic-disease epidemic. More about Dr. Hyman or on Functional Medicine. Click here to view all Press and Media Releases

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Academic takes a well-aimed swipe at cholesterol drug ezetimibe - Briffa

Academic takes a well-aimed swipe at cholesterol drug ezetimibe

Aug, Fri 24th, 2012  By : Dr John Briffa

 

I am not particularly enthusiastic about cholesterol management. I don’t believe that the role cholesterol has in cardiovascular disease is as is popularly stated. But more importantly, when we use drugs to manage cholesterol the results are, by and large, disappointing. For example, treatment with statins does not save lives in people without a prior history of heart attack or stroke. Even in people at higher risk of cardiovascular disease, the great majority of treated individuals over a few years will not benefit. And then we have the problems of side effects.

The popularity of cholesterol management strategies in many way hinges on the idea that (LDL) cholesterol is bad, and lowering it is good. Yet, the scientific literature is littered with evidence that does not support either of these contentions. For example, we have evidence linking higher cholesterol levels with improved health outcomes and longevity in the elderly. We also have plenty of evidence which shows that cholesterol reduction will not always benefit health, and may in fact pose hazards here.

A case in point here concerns the drug ezetimibe. This medication reduces cholesterol, but unlike statins (which reduce cholesterol production in the liver), ezetimibe blocks the absorption of cholesterol from the gut. It’s generally very effective at reducing cholesterol levels, and because of this, the Food and Drugs Administration (FDA) licensed ezetimibe for use in the treatment of raised cholesterol in 2002. Since then, ezetimibe has gone to rack up sales in the order of $4 billion dollars annually.

Ezetimibe was licensed on the basis of its ability to lower cholesterol. At this time, no study has been published that it had benefits on health. So, what’s happened since? Well, there’s been a few studies that have looked at ‘clinical’ endpoints or disease processes (such as the build-up of plaque in the arteries), and the results have been far from encouraging.

For example, 2008 saw the publication of the so-called ENHANCE study which found that adding ezetimibe to simvastatin (a statin) led to an increase in the thickness of artery walls in the neck compared to simvastatin alone (though the difference was not statistically significant). The results of this trial were delayed by 2 years and had to be forced out of the manufacturers by the US Government.

Other studies have not only found no benefit, they’ve revealed worsening outcomes. In one study, treatment with ezetimibe was associated with (statistically significant) worsening of the narrowing of the arteries in the legs [1]. And then we have the inconvenience of the trials which link ezetimibe use to an increased risk of dying from cancer [2], which some researchers (in the pay of ezetimibe’s manufacturers) put down to ‘chance’, even though the data shows that the association is highly unlikely to be due to chance, and in all likelihood is a real effect.

Casual conversations with members of the medical profession reveal to me that the issues with ezetimibe are largely unrecognised, though there have been signs in the scientific literature that we are at last seeing some awareness of the issues. I came across a piece published recently in the journal Expert Opinion in Pharmcotherapy written by Dr Sheila Doggrell of the University of Queensland in Australia [3]. Dr Goggrell has reviewed the evidence and concludes this:

“…ezetimibe alone or in the presence of simvastatin has not been shown to have any irrefutable beneficial effects on atherosclerosis or cardiovascular morbidity and mortality. Thus, until/unless the use of ezetimibe is clearly shown to improve clinical outcomes, its use should be largely restricted to clinical trials investigating clinical outcomes and should not be used routinely in everyday practice.”

It is perhaps relevant that Dr Doggrell is an academic, which perhaps gives her the tools to take a cool hard look at the data and come to her own conclusions. Despite not being a clinician she is acutely aware that the only important thing is the impact ezetimibe has on health (not cholesterol levels). It’s an approach that I think more clinicians could do with adopting.

References:
1. West AM, et al. The effect of ezetimibe on peripheral arterial atherosclerosis depends upon statin use at baseline. Atherosclerosis. 2011;218(1):156-62
2. Peto R, et al. Analyses of cancer data from three ezetimibe trials. NEJM 2008;359(13):1357-66
3. Doggrell SA. The ezetimibe controversy – can this be resolved by comparing the clinical trials with simvastatin and ezetimibe alone and together? Expert Opin Pharmacotherapy 2012;13(10):1469-80
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Emphasis of bold text added by me - bd. Read thecomplete article here.

The hidden truth about statins

June 12, 2010   by Chris Kresser

 

Statins are the most popular drugs in history. Drug companies made $26 billion selling statins alone in 2008. 25 million Americans take them, and the number is growing each year.

One reason why statins are the best-selling drug category by far is that 92% of people taking them are healthy. The FDA has approved the prescription of statins to people at low risk for heart disease and stroke, who don’t even have high cholesterol. Two years ago the American Academy of Pediatricians recommended that statins be prescribed for kids as young as eight years old.

With sales statistics like this, you’d think statins are wonder drugs. But when you look closely at the research, a different story emerges. Statins have never been shown to be effective for women of any age, men over 65, or men without pre-existing heart disease. Early studies did suggest that statins are effective for men under 65 with pre-existing heart disease, but later, more rigorous clinical trials has not confirmed this benefit.

In addition, statins have been shown to have serious side effects and complications in up to 30% of people who take them. Studies have also shown that the majority of these adverse events go unreported, because doctors are largely unaware of the risks of statins.

Watch the two videos below to learn the whole story. Or, you can read this article for a concise summary of the evidence.

Video Presentation

link

Handouts

• Statin research summary: lists the eight statin studies performed in 2008 – 2009, including the drugs and populations studied and the results. If you’re currently taking a statin, you might consider printing this out and taking it to your doctor as a springboard for a conversation about whether statins are right for you.

References

ENHANCE
KasteleinJJ, AkdimF, StroesES, for ENHANCE investigators. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med 2008;358:1431-43
CASHMERE
O’Riordan M. CASHMERE: no IMT effect with atorvastatin over 12 months. (link)
ACHIEVE
O’Riordan M. ACHIEVE stopped: IMT study with Niacin/Laropiprant halted by Merck & Co. (link)
SEAS
Rossebø AB, Pedersen TR, Boman K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med 2008;359:1343-56
GISSI-HF
GISSI-HF Investigators, Tavazzi L, Maggioni AP, Marchioli R, et al. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomized, double-blind, placebo-controlled trial. Lancet 2008;372:1231-9
CORONA
Kjekshus J, Apetrei E, Barrios V, et al. Rosuvastatin in older patients with systolic heart failure. N Engl J Med 2007;357:2248-61
AURORA
Fellström BC, Jardine AG, Schmieder ME, et al for the AURORA study group. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med 2009;360:1395-407
JUPITER
Ridker PM, Danielson E, Fonseca FA, et al, for the JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-Reactive protein. N Engl J Med 2008;359:2195-207

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FDA: Atorvastatin/ezetimibe combo needs more data

This from The Heart.org

Vytorin has been plagued by controversy in recent years, particularly given the lack of benefit with the drug in the Effect of Combination Ezetimibe and High-Dose Simvastatin vs Simvastatin Alone on the Atherosclerotic Process in Patients with Heterozygous Familial Hypercholesterolemia (ENHANCE) trial. In addition, many in the clinical community have criticized the company, as well as the FDA, for the delays in reporting hard clinical outcomes data with the ezetimibe/simvastatin combination. The Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) study is currently expected to be completed in June 2013.


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Statin Drugs linked to rise in Diabetes

from Mercola.com

By Suzy Cohen, R.Ph.

Coronary heart disease is a leading cause of death in the United States, killing one in five adults, and doctors are very quick to prescribe statins. In fact, statin drug sales rank in the billions each year globally.

These drugs are so pervasive that they are no longer just indicated for hypercholesterolemia, they are also being prescribed for elevations in C reactive protein, and are promoted for kids as young as eight years old.

Heart disease is so pervasive that some have boldly suggested that we should put statins in our water supply as some kind of protection.

This is very disturbing.

Do You Really Need a Statin Drug?

By far, statin drugs are the most popular cholesterol-lowering drugs available today. They work in your liver by preventing your body from making cholesterol. The drugs block an enzyme called HMG-CoA Reductase. This can be helpful, but only if you are one of those people who happen to produce too much cholesterol.
It doesn’t do a good job at removing it from your clogged arteries, contrary to what most people think.
Physicians and health experts now agree that statins seem to offer more benefit through their ability to reduce dangerous inflammatory chemicals in your body, rather than by reducing production of cholesterol, which usually leads to uncomfortable, unwanted and dangerous side effects. One study found that lowering cholesterol too much actually backfires.
Cholesterol is good for you; it’s one of your body’s most powerful antioxidants, it makes important neurotransmitters and sex hormones so this madness to lower it as much as possible really concerns me. Plus, I believe the indiscriminate use of statins has contributed to the staggering rise in diabetes…

The Statin—Diabetes Connection Few People Know About

I watched this happen to my mom who was given a statin, and then told months later she suddenly had diabetes. All of a sudden? This happened many years ago, and it began my search to understand the connection. It also prompted me to write a book on the subject entitled “Diabetes Without Drugs” (Rodale, 2010).
It typically happens like this:
Many statin users come back to see their physician for a routine visit and after the blood work is drawn, they find their cholesterol ratios may be improved, but now they have high blood glucose.
It’s entirely possible that some physicians then mistakenly diagnose their patients with “Type 2 diabetes” when in fact they just have hyperglycemia—a side effect, and the result of a medication that was prescribed to them months earlier.
Do you think you have type 2 diabetes?
I will provide more information so you can see for yourself that so-called “diabetes” diagnosis might not really be genuine diabetes. It may just be hyperglycemia (high blood sugar)—the result of your cholesterol medication, and for some people, it may be reversible with drug discontinuation. Whether or not you are able to discontinue your medication is between you and your physician.

Research Suggesting Raised Blood Sugar is a Side Effect of Statin Use

Several studies have indicated that statins can cause high blood sugar, which can be mistaken for “diabetes.” For example, researchers in Glasgow, Scotland conducted a meta analysis, known as the JUPITER trial, which took into account 13 statin trials that each included 1,000 patients or more. The participants were followed for over than a year. The conclusion was there was indeed an increase, albeit small, in the development of Type 2 diabetes.
It should be considered that some of the patients in this meta analysis already had symptoms of insulin resistance or metabolic syndrome, so it could be said that they were on their way to diabetes anyway.
Now consider another meta-analysis published in the Lancet Here, the researchers reviewed randomized controlled trials beginning in 1994 and ending in 2009, for a total of 91,140 participants who took either a statin or a placebo.
They found that people treated with statin drugs showed a nine percent increase for diabetes. They did not evaluate other factors however, which would be considered pre-diabetes, so I suspect their nine percent number to be on the low side.
Insulin is a pancreatic hormone that reduces blood sugar. You want some insulin to maintain blood glucose levels, but too much of it is bad—it’s an inflammatory compound in your body when it is elevated. And guess what? The use of statin drugs appears to INCREASE your insulin levels! High insulin is extremely harmful to your health.
For starters, elevated insulin levels lead to heart disease, and isn’t that the reason cholesterol drugs are prescribed in the first place?
The ratio of glucose to insulin should be less than 10:1, this ratio is far more important than the levels of glucose or insulin alone. Keep that in mind if you seek a complete recovery. For more information about the harmful effects of elevated insulin levels, see my article on dearpharmacist.com, or my book Diabetes Without Drugs.
You want to keep insulin normal, to protect yourself from heart disease and high blood pressure. Chronically elevated insulin causes a cascade of inflammatory chemicals and high cortisol which lead to belly fat, high blood pressure, heart attacks, chronic fatigue, thyroid disruption, plus major diseases like Parkinson’s, Alzheimer’s and cancer.
Unfortunately, the most popular cholesterol drugs in the world seem to increase insulin levels. However, that’s just one mechanism by which these drugs can raise your risk for diabetes.

How Statins Raise Your Insulin

Keeping things simple, you might imagine it like this: When you eat a meal that contains starches and sugar, some of the excess sugar goes to your liver, which then stores it away as cholesterol and triglycerides. Now stay with me — when you have a statin on board, it’s like a message to your liver saying, “No! Don’t make any more cholesterol, please stop.”
So your liver sends the sugar back OUT to your bloodstream. As a result, your blood sugar goes up.
In 2009, it was proven that statins could directly raise blood sugar, whether or not you have diabetes. Over 340,000 people were included before this conclusion was made. The people who did not have diabetes but took statins experienced a rise in blood glucose from 98 mg/dl to 105 mg/dl. Those who already had diabetes and also took statins experienced a rise from 102 mg/dl to 141 mg/dl.
After adjustments for age and medication use were considered, researchers concluded that both diabetic and non-diabetic statin users showed a statistically significant rise in blood sugar.
Why take all these risks, just to get the convenience of taking a pill instead of eating a better diet and exercising?
It’s been scientifically discussed and even published in JAMA that eating a better diet could lower cholesterol as well as the statin drug lovastatin.
And of course, there are so many other benefits to eating a healthier diet that consists of fruits, vegetables, nuts, seeds, and lean meats. Besides feeling better and increasing lifespan, you can squeeze into those skinny jeans you’re hiding in your closet.
Another way statins can affect your blood sugar is via their “drug mugging” effect. A drug mugger is my term, and the title of my newest book, which describes how a drug can rob your body’s warehouse of a valuable nutrient. In the case of statins, they rob your body of two different nutrients, both of which are needed to maintain ideal blood sugar.

Two Important Nutrients Decimated by Statins

The first nutrient that is mugged is vitamin D. There have been mixed studies regarding the D-depletion effect of statins, but statins reduce your body’s natural ability to create active vitamin D called 1,25-dihydroxycholecalciferol, shortened to “calcitriol” when it is eventually converted to its active hormone form.
This happens because statins reduce cholesterol, and you need cholesterol to make vitamin D! It is the raw material that exposure to UVB from sunlight will convert to vitamin D.
It is well documented that D improves insulin resistance, so needless to say, when you take a drug mugger of vitamin D (like statins), then you increase your risk for diabetes.
More specifically, a 2004 study published in the American Journal of Clinical Nutrition determined that raising a person’s serum vitamin D levels (from 25 to 75 nmol/l) could improve insulin sensitivity by a whopping 60 percent.
Compare that to the blockbuster diabetes drug metformin, one of our pharmaceutical gold-standards, which can dispose of blood sugar by a meager 13 percent according to the New England Journal of Medicine.
Now, statins also suppresses your natural coenzyme Q10— also called “ubiquinol” in its active form; it makes energy for every cell in your body, and it’s produced mainly in your liver.
This powerful antioxidant just so happens to also play a role in maintaining blood glucose. When you deplete levels of CoQ10 by taking a drug mugger of it, like a statin drug, then you lose that benefit. You also raise your risk for heart failure, high blood pressure and heart disease as CoQ10 deficiencies can contribute to those conditions. A study by Hodgson et al, published in 2002 found that 200mg CoQ10 taken daily caused a 0.4 percent reduction in hemoglobin A1c.
Moreover, CoQ10 protects your body from oxidative stress, a strong contributing factor in the development of diabetes, metabolic syndrome and heart attacks. You want to make sure you have enough CoQ10 (or ubiquinol) on board to protect every cell in your body. The take home point is that statins annihilate this compound and you need it for good health.
In summary, if you take a statin medication and you’ve been told that you have diabetes, it may be drug-induced, and it’s possible that it can be reversed over the course of time. However, you will have to eat right, exercise, and take supplements that help to lower your risk for heart disease naturally.
About the Author
Suzy Cohen, R.Ph., has been a licensed pharmacist for 22 years, and has had a weekly syndicated health column for the past 13 years which you can get for free by signing up at her website Widely recognized as “America’s most trusted pharmacist,” she has appeared on The Dr OZ Show, The View, Good Morning America Health and The 700 Club.
Cohen is also the author of three books: The 24-Hour Pharmacist, Diabetes Without Drugs, and Drug Muggers: Keep Your Medicine from Stealing the Life Out of You.
For more information, see www.SuzyCohen.com.

Sources:
Journal of the Federation of American Societies for Experimental Biology May 1, 2004; 18(7): 805-815
Journal of Investigative Medicine March 2009; 57(3): 495-499
About.com February 20, 2010
The Lancet February 2010; 375(9716): 735 – 742
The Lancet February 27, 2010; 375(9716): 700 – 701
Reuters March 10, 2011
International Journal of Obesity February 8, 2011 [Epub ahed of print]
American Heart Journal (ENHANCE trial) February 2005; 149(2): 234-239
Lancet February 27, 2010; 375(9716): 735-42
Journal of Investigative Medicine March 2009; 57(3): 495-499
JAMA 2003;290(4):502-510
=====================================
Read article with comments here  http://articles.mercola.com/sites/articles/archive/2011/03/28/the-stealth-drug-cause-of-diabetes.aspx

The Cholesterol Theory of Heart Disease is Nonsense

Anthony Colpo who I have learned much from especially back in the days he was regularly putting out good analysis of many health items on The Omnivore.com. Here is a new newsletter I just saw published on the_omnivore@yahoogroups.com. I've provided it in full here. It is a bit long but thorough as I have found him to be. Thank You Anthony!
================================================
The Cholesterol Theory of Heart Disease is Nonsense
Posted by: "theomnivorenewsletter" ac.theomnivore@gmail.com theomnivorenewsletter
Sun Jan 3, 2010 4:30 pm (PST)


The Cholesterol Theory of Heart Disease is Nonsense

I've been telling people for years that the anti-cholesterol,
anti-saturated fat paradigm is not only nonsense but potentially
dangerous. The latest confirmation of my stance comes from two recent
studies that - in stark contrast to vigorously hyped anti-cholesterol
research – have been ignored by the mainstream health media.

The most recent of these studies was published in the November 15, 2009
issue of the New England Journal of Medicine. The ARBITER 6–HALTS
trial compared the effects of two combination therapies - either
ezetimibe+statins or niacin+statins - on carotid intima-media thickness
over a 14-month period. Measurement of carotid artery intima-media
thickness is used to indicate the extent of atherosclerosis and for
assessing cardiovascular risk.

All of the 363 subjects enrolled in the trial were already taking
cholesterol-lowering statin drugs. Statin drugs have become the darlings
of the medical establishment due to their ability to lower both total
and LDL cholesterol, while ezetimibe has become a popular adjunct to
statin treatment thanks to its LDL-lowering actions. The subjects were
randomly assigned to receive either extended-release niacin at a target
dose of 2000 mg per day or ezetimibe at a dose of 10 mg per day. The
niacin was increased from an initial dose of 500 mg at bedtime, by 500
mg every other week, to the maximum tolerated dose (up to 2000 mg at
bedtime).

The subjects were men and women (mean age 65) with atherosclerotic
cardiovascular disease or a coronary heart disease (CHD) risk
equivalent, including diabetes, a 10-year Framingham risk score of 20%
or more, or a coronary calcium score above 200 for women or 400 for men.

A total of 208 patients had completed 14 months of treatment when the
study was called to a halt. Initial LDL levels were similar in both
groups, but etezimibe produced greater reductions in LDL than niacin
(-17.6 mg/dl vs -10.0 mg/dl). If you believe the relentless barrage of
anti-LDL propaganda emanating from our ever-so-wise, impartial,
objective and totally incorruptible health authorities, then this should
have produced greater improvements in the etezimibe group.

But it didn't.

When the data was analyzed, it was observed that niacin produced a
significant reduction in carotid intima-media thickness at both 8 and 14
months. No significant overall change in carotid intima-media thickness
was seen with ezetimibe.

The researchers did however find a significant inverse relationship
between changes in LDL cholesterol and carotid intima-media thickness in
the ezetimibe group, such that a "paradoxical" increase in the
carotid intima-media thickness was seen in patients with greater
reductions in LDL cholesterol (rather than simply acknowledge the
cholesterol theory is bollocks, researchers invariably label any and
every uncomfortable contradiction to this theory a "paradox").

Major adverse cardiovascular events also occurred at a significantly
greater rate in the ezetimibe group (9 of 165 patients [5%]) than in the
niacin group (2 of 160 patients [1%]).

A peek at the dropout data also reveals some interesting findings. Among
363 patients enrolled in the trial, 44 had left the study by the time it
was terminated on June 4, 2009: 16 of 176 (9%) in the ezetimibe group
(of whom 9 had been withdrawn and 7 had died) and 28 of 187 (15%) in the
niacin group (of whom 27 had been withdrawn and 1 had died). Adverse
drug effects were cited as the reason for withdrawal in 3 of 9 patients
receiving ezetimibe and 17 of 27 patients receiving niacin. The
well-known side effect of flushing was reported in 36% of patients in
the niacin group[1].

Bottom line: Ezetimibe produced greater reductions in LDL cholesterol
(the so-called "bad" cholesterol) but resulted in no overall
improvement in carotid intima-media thickness, while individual results
showed greater thickening with greater LDL reductions. The use of
etezimibe was also accompanied by a higher number of heart attacks and
deaths.

Yep, the "paradoxes" flowed thick and fast in this study. Of
course, those of you who have read The Great Cholesterol Con will know
that there was absolutely nothing paradoxical about these findings –
the cholesterol theory is, and always has been, utter nonsense.

So Popular But So Useless

This is hardly the first time ezetimibe has shown itself to be a dud.
The SANDS trial, examining type 2 diabetic American Indians, found that ,
ezetimibe plus statins produced no greater improvement in carotid
intima-media thickness than statins alone[2].

In the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial, 1873
patients with mild-to-moderate, asymptomatic aortic stenosis (abnormal
narrowing of the heart's aortic valve) received either 40 mg of
simvastatin plus 10 mg of ezetimibe or placebo daily. During a follow-up
of 52.2 months, simvastatin and ezetimibe, as compared with placebo, did
not reduce the composite outcome of combined aortic valve events and
ischemic events in patients with aortic stenosis.

The simvastatin–ezetimibe group did however experience something
that the placebo group did not: an increased cancer risk. A
statistically significant excess of incident cancers was observed in the
simvastatin– ezetimibe group, with 105 in that group as compared
with 70 in the placebo group. In addition, deaths from cancer were more
frequent in the simvastatin– ezetimibe group (39 deaths vs. 23 in
the placebo group). There was also a significant increase in the number
of patients with elevated liver enzyme levels in the
simvastatin–ezetimibe group[3].

Increased cancer risk from cholesterol-lowering drugs has been observed
previously. In the PROSPER study featuring elderly subjects - the
demographic in whom you would most likely expect an increased cancer
risk to manifest itself during the relatively short duration of a
clinical trial - an increased mortality from malignant causes among
those taking pravastatin negated the reduction in cardiovascular
deaths[4]. Etezimibe, meanwhile, inhibits the absorption of phytosterols
and other phytonutrients linked to protection against cancer[5].

The ENHANCE trial was a double-blind, randomized, 24-month endeavour
comparing the effects of 80 mg of simvastatin combined with either with
placebo or with 10 mg of ezetimibe daily in 720 patients with familial
hypercholesterolemia. Mean levels of LDL cholesterol decreased from
317.8 mg/dl per to 192.7 mg/dl in the simvastatin-only group and from
319.0 mg/dl to 141.3 mg/dl in the combined-therapy group. Despite their
significantly greater decrease in LDL levels, the simvastatin+ ezetimibe
group experienced no statistically significant greater decrease in
carotid intima-media thickness.

Nor was there any advantage in incidence of regression in mean
carotid-artery intima–media thickness or new plaque formation. No
significant change was observed in mean maximum carotid-artery
intima–media thickness, mean measures of the intima–media
thickness of the common carotid artery, the carotid bulb, the internal
carotid artery, the femoral artery, nor in the average of the mean
values for intima–media thickness in the carotid and femoral
arteries. Investigator-reported cardiovascular events were noted in
seven patients in the simvastatin group (including 1 death from a
cardiovascular cause, 2 nonfatal myocardial infarctions, 1 nonfatal
stroke, and 5 coronary revascularization procedures) and in 10 patients
in the combined-therapy group (including 2 deaths from cardiovascular
causes, 3 nonfatal myocardial infarctions, 1 nonfatal stroke, and 6
coronary revascularizations)[6].

Since its introduction in 2002, ezetimibe has become the primary adjunct
to statins for reducing "elevated" LDL. This is despite the fact
that it has so far shown itself to be totally incapable of actually
producing any meaningful health benefit for the people who take it. In
today's bizarro drug company-owned health arena, where cholesterol
reduction has become a sacred end in itself, a woeful inability to
reduce heart attack or death is swept aside as a minor inconvenience.
There's money to be made in them thar lipid-lowering drugs, to hell
with any profit-destroying notion that they are largely a waste of time
and money…

WHO Says the Saturated Fat Theory is Garbage?

A recent special issue of Annals of Nutrition and Metabolism was devoted
to "Fats and Fatty Acids in Human Nutrition". This issue was the
result of a joint FAO/WHO Expert Consultation held in Geneva, November
2008 and contains "the background papers which have been prepared by
a panel of carefully selected experts and have served as the basis for
the updated dietary recommendations of FAO and WHO"[7]

One of the papers presented in this special report was a sweeping review
of both prospective epidemiological studies and clinical trials
examining the relationship between dietary fat and CHD[8]. This review
was conducted by researchers from the Department of Human Nutrition at
the University of Otago, Dunedin , New Zealand.

I must confess that when I initially pulled up the PDF of this study
(which you can freely access from the link below), I was fully expecting
more of the same old fat- and cholesterol-phobic hoopla that has
regrettably characterized public health recommendations for almost half
a century. Instead, I was pleasantly surprised. In fact, pleasantly
shocked is a more fitting description. Despite being published under the
auspices of one of the world's largest health organizations, the
report actually tells…the truth!

After examining 28 prospective epidemiological studies, the researchers
reported that:

"Intake of total fat was not significantly associated with CHD
mortality..." (p. 175)

"Intake of total fat was also unrelated to CHD events..." (p. 175)

"Intake of TFA [trans fatty acids] was strongly associated with CHD
mortality..." (p. 181)

"Intake of SFA [saturated fatty acids] was not significantly associated
with CHD mortality...

Similarly SFA intake was not significantly associated CHD events..." (p.
181)

Their pooled analysis of data from randomized controlled clinical trials
showed:

"...fatal CHD was not reduced by either the low-fat diets... or the high
P/S diets [diets high in polyunsaturated fats and low in saturated fats]
...". (p. 188)

On page 193, they conclude:
"There is probably no direct relation between total fat intake and risk
of CHD."

If you were expecting this rare gem of health authority-sanctioned
honesty and factual reporting to be reflected in said health
authority's dietary recommendations to the public, then you clearly
know little about the mechanics of these anachronistic juggernauts.
Maintaining the status quo is a self-serving activity of utmost
importance to reigning orthodoxies. Changes to currently accepted diet
and health recommendations occur almost imperceptibly over time, as
small modifications that "advance" the current body of knowledge
but never upset the underlying foundational dogma itself. Such
modifications typically include the inclusion of politically acceptable
discoveries (such as the cardiovascular benefits of omega-3 fatty acids
from fish and fish oils). However, the wholesale embrace of politically
incorrect findings is unthinkable. As such, the world's health
authorities continue to preach the kind of nonsense that rational minds
would associate with the ignorant, superstitious thinking of the Dark
Ages. Such nonsense includes the belief that cholesterol, an essential
life-sustaining substance that Mother Nature saw fit to include in the
membranes of all our cells, to protect our nervous systems, and to use
as the basis for production of our most important hormones, is in fact
toxic and must be lowered at all costs.

And so it is in this case: despite the conclusions of the aforementioned
review, WHO are still currently preaching the same old
anti-cholesterol/anti-saturate hogwash in their CHD prevention
guidelines[9].

Where's Your Head at?

Some of you reading this will do further investigation and will conclude
of your own volition that what I have reported above is factual. Some of
you will be confused and will not know what to make of what I have just
reported; it sounds compelling but at the same time you have great
difficulty accepting that so many "prestigious" health
authorities, government bodies, medical associations, doctors,
journalists, authors, and numerous other assorted talking heads could be
so wrong. Such a mindset reveals a rather naïve understanding of
human nature. No matter how prestigious and well-funded the organization
or profession, it is still comprised of fallible human individuals with
a deep-rooted evolutionary-programmed tendency to follow the herd and
subscribe to groupthink.

A minority of readers will even become angry at what I have just
written, offended by my temerity to report facts which so blatantly
contradict what they have come to believe. My response to those who fall
into this category is…too bad. After years of coming under attack
from the disgruntled worshippers of various scientifically untenable
nutrition paradigms, I'm totally over trying to reason with the
unreasonable. My aim is simply to relay research findings to those who
may find the information useful, not to pander to the fragile
sensibilities of those who attain emotional solace in certain diet and
health beliefs.

Life, if you allow it to be so, is a fascinating voyage of continual
discovery. If you wish to make any meaningful progress during this
voyage, you will frequently need to re-examine beliefs that you have
become comfortable with, and you must be prepared to discard these
beliefs if the evidence dictates.

For those prepared to do this, and who would like to further examine the
contrarian side of the cholesterol story, may I recommend the following
resources:

1. The Great Cholesterol Con by yours truly. Yes, it's my
own book and after years of extensive research and effort I would
of course be expected to gush on about what a wonderfully
ground-breaking, enlightening and beneficial tome it constitutes.
So don't listen to me; check out the non-partisan reviews by
Amazon customers and folks like Chris Masterjohn, who considers the book
"the most well-written and well-researched book on the
"skeptic" side of the debate":

http://www.cholesterol-and-health.com/Anthony-Colpo-Great-Cholesterol-Co\
n.html


A review of TGCC by Joel Kauffman can be viewed here:

http://www.jpands.org/vol11no4/bookreviews.pdf


The Amazon page for The Great Cholesterol Con can be found here:

http://www.amazon.com/Great-Cholesterol-Con-Anthony-Colpo/dp/1430309334


Those of you looking to save some money and wanting instant access to
the book can get an ebook version here:

http://www.thegreatcholesterolcon.com/


NOTE: To those of you who purchase my book (or already have it), please
read Chapter 22 – over and over. Judging by the reviews and comments
I have read about my book, that chapter appears to be overlooked by many
readers. Yet if you are truly serious about preventing coronary heart
disease, it contains the most valuable information you may ever come
across.

1. My freely available article on LDL cholesterol, which appeared in
the Journal of American Physicians and Surgeons:
http://www.jpands.org/vol10no3/colpo.pdf


Also a letter of criticism and my reply:
http://www.jpands.org/vol11no1/correspondence.pdf


1. Fat and Cholesterol are Good for You by Uffe Ravnskov. Don't
be fooled by the Atkins-like title; Uffe is a serious and
meticulous researcher with dozens of peer-reviewed research papers
to his name. I consider his writings essential reading for anyone
interested in the cholesterol debate. His book can be obtained
here:
http://www.amazon.com/Fat-Cholesterol-are-Good-You/dp/919755538X/ref=pd_\
sim_b_2


Uffe also heads a group called THINCS, whose website contains various
articles and links to resources articulating skeptical views of the
cholesterol theory:
http://www.thincs.org/

The website contains some great information; the page devoted to
unpublished correspondence (critical letters that were knocked back by
the journals they were submitted to) makes for especially
interesting reading. Please note this does not constitute a blanket
endorsement by myself of THINCS – while I find myself agreeing
with almost everything Uffe writes, I don't agree with some of
the assertions made by certain other THINCS members/contributors. I
would urge readers to be especially wary of authors who make
untenable claims about the superiority of isocaloric low-carb diets
for weight loss (claims that have been repeatedly disproved in
tightly controlled ward studies), and those who claim to have
discovered a single unifying cause of CHD whilst ignoring the critical
role of such factors as bodily iron stores, nutrition (especially
refined carbohydrate intake), vitamin and mineral status (most
notably magnesium), infectious disease, omega-3:omega-6 status,
physical activity, obesity, and/or stress.

2. Statin Drugs Side Effects and the Misguided War on Cholesterol by
Duane `Spacedoc' Graveline. This former astronaut and
physician was a key figure in alerting the public to the
little-known statin side effect of transient memory loss, which has
since been the subject of peer-reviewed articles and case reports.
Those who are being cajoled by their doctors to begin statin drug
use would be well advised to read this book:
http://www.amazon.com/Statin-Drugs-Effects-Misguided-Cholesterol/dp/0970\
081790


All the best,

Anthony Colpo.

References

1. Taylor AJ, et al. Extended-release niacin or ezetimibe and
carotid intima-media thickness. New England Journal of Medicine,
Nov 26, 2009; 361 (22): 2113-2122.
2. Fleg JL, et al. Effect of Statins Alone Versus Statins Plus
Ezetimibe on Carotid Atherosclerosis in Type 2 Diabetes. The SANDS
(Stop Atherosclerosis in Native Diabetics Study) Trial. Journal of
the American College of Cardiology, 2008; 52: 2198-2205.
http://content.onlinejacc.org/cgi/reprint/j.jacc.2008.10.031v1.pdf

3. Rossebø AB, et al. Intensive lipid lowering with
simvastatin and ezetimibe in aortic stenosis. New England Joural of
Medicine, 2008; 359: 1343-1356.
http://content.nejm.org/cgi/reprint/359/13/1343.pdf

4. Shepherd J, et al. PROspective Study of Pravastatin in the
Elderly at Risk. Pravastatin in elderly individuals at risk of
vascular disease (PROSPER): a randomised controlled trial. Lancet,
2002; 360: 1623-1630.
5. Bradford PG, Awad AB. Phytosterols as anticancer compounds.
Molecular Nutrition & Food Research, 2007; 51: 161-170.
6. Kastelein JJ, et al. Simvastatin with or without ezetimibe in
familial hypercholesterolemia. New England Joural of Medicine, Apr.
3, 2008; 358 (14): 1431-1443.
http://content.nejm.org/cgi/reprint/358/14/1431.pdf

7. Fats and Fatty Acids in Human Nutrition. Annals of Nutrition and
Metabolism, 2009; 55 (1-3). Available online:
http://content.karger.com/ProdukteDB/produkte.asp?Aktion=showproducts&se\
archWhat=books&ProduktNr=251867

8. Skeaff MC, Miller J. Dietary Fat and Coronary Heart Disease:
Summary of Evidence from Prospective Cohort and Randomised
Controlled Trials. Annals of Nutrition and Metabolism, 2009; 55:
173–201.
http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&Artikel\
Nr=229002&Ausgabe=250361&ProduktNr=223977&filename=229002.pdf

9. http://www.fao.org/DOCREP/005/AC911E/ac911e07.htm#bm07.4.3


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**DISCLAIMER**
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information.