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Thursday, August 14, 2014

More SALT Controversy - Nestle

It’s salt war time again: new research, arguments over public health recommendations, and issues of conflicts of interest

Here are the burning questions about sodium (which is 40% of salt) intake:
(a) Does too much dietary sodium cause high blood pressure?   Answer: an unambiguous yes (although not necessarily in everyone).
(b) Are public health recommendations to reduce salt intake warranted?  I think so, but others disagree.
(c) If so, to what level?  Although virtually all committees reviewing the evidence on salt and hypertension view public health recommendations as warranted, and advise an upper limit of about 2 grams of sodium (5 grams of salt, a bit more than a teaspoon (see table from the Wall Street Journal), these too are under debate.

These recommendations are strongly opposed by The Salt Institute, the trade association for the salt industry, its industry supporters, and some groups of investigators.
Now the New England Journal of Medicine weighs in with three new studies, an editorial, and a cartoon video.  The papers:
Start with the video,  narrated by the editor, Dr. Jeffrey Drazen (click on video link on the right side).  It gives an excellent summary of the three papers.  Despite their methodological differences, all confirm (a).  They disagree on (c) and, therefore, (b).

Are public health recommendations warranted?
But note Dr. Drazen’s suggestion: “throw away the salt shaker.”
He is in favor of reducing salt intake.  But the salt shaker is not where most dietary salt comes from.  At least 75% of salt in American diets comes from restaurant and processed foods.   As Dr. Yoni Freedhoff explains:
If you’d like to reduce the sodium in your diet, rather than keep a running tally of how much you’re actually consuming, why not try instead to determine what percentage of your diet comes from restaurants and boxes? Sure, there’s data to suggest you might simply find other ways to add salt to your diet. But visit restaurants and consume processed foods less frequently, and I’d be willing to wager that you’ll be far more likely to see health benefits than were you to simply fill your grocery cart with low-sodium versions of highly processed foods.
Individuals cannot cut down on salt on their own.  That’s one reason why public health policies are needed—to get restaurants and processed food manufacturers to reduce salt content.
Two of the papers say that the only people who need to cut down on salt are those with hypertension and older people (one of the studies says that means people over age 55).
You can’t expect 70 or 80 million people to reduce salt intake on their own.  Hence: public health recommendations.

Conflict of interest alert
Some of the investigators report receiving grants or fees from companies that make anti-hypertensive drugs but the editorial accompanying the papers is of special concern.   Written by Dr. Suzanne Oparil, it says about one of the studies:
These provocative findings beg for a randomized, controlled outcome trial to compare reduced sodium intake with usual diet. In the absence of such a trial, the results argue against reduction of dietary sodium as an isolated public health recommendation.
These conclusions sent me right to her conflict-of-interest disclosure statement.  Although Dr. Oparil reports receiving grants or fees from companies making anti-hypertensive drugs—-and, even more remarkable, from The Salt Institute—she states that she has no conflicts of interest.
I think she does.

Implications
Her editorial is especially unfortunate because it influences the way reporters write about the studies.
The Associated Press account, for example, begins:
A large international study questions the conventional wisdom that most people should cut back on salt, suggesting that the amount most folks consume is OK for heart health — and too little may be as bad as too much. The findings came under immediate attack by other scientists.
As well they should.  Blood pressure rises with age and huge swaths of the population would be healthier eating less salt.   The AP reporter quoted me saying so:
“People don’t eat salt, they eat food,” she said. “Lots of people have high blood pressure and lots of people are getting older,” making salt a growing concern, she said. “That’s the context in which this is taking place.”
The three studies are complicated to interpret because of differences in methods and discrepancies in outcomes.  They agree that if you already have hypertension or are “elderly,” or eat a lot of salt, you should cut down.

This seems like a good idea for just about anyone.   People don’t eat salt; they eat foods containing salt, and foods high in salt tend to be high in other things best consumed in small amounts.
The studies also talk about the protective effects of potassium, best obtained from vegetables.
Eat a lot of vegetables and not too much junk food, and you don’t have to worry about any of this.
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Read the complete article here.

Wednesday, August 6, 2014

The Lancet published a meta-analysis of 27 statin trials

Data, Drugs, and Deception: a True Story

 
Last week The Lancet published a meta-analysis of 27 statin trials, an attempt to determine whether patients with no history of heart problems benefit from the drugs—true story. The topic is controversial, and no less than six conflicting meta-analyses have been performed—also a true story. But last week’s study claims to show, once and for all, that for these very low risk patients, statins save lives—true story.

Actual true story: the conclusions of this study are neither novel nor valid.

The Lancet meta-analysis, authored by the Cholesterol Treatment Trialists group, examines individual patient data from 27 statin studies. Their findings disagree with an analysis published in 2010 in the Archives of Internal Medicine, and with analyses from two equally respected publications, the Therapeutics Letter and the Cochrane Collaboration.* Despite this history of dueling data the authors of last week’s meta-analysis, in a remarkable break from scientific decorum, conclude their report with a directive for the writers of statin guidelines: the drugs should be broadly recommended based on the new analysis.

As an editorialist points out, if implemented, the CTT group recommendations in the United States would lead to 64 million people, more than half of the population over the age of 35, being started on statin therapy—true story.

Where is the magic, you ask, in this latest effort? What is different? In some ways, nothing. Indeed just a year and a half earlier The Lancet published a meta-analysis of 26 of the same 27 studies, with the same results, by the same authors (true story, and an odd choice on the part of the journal). So the findings aren’t new. They are, however, at odds with other meta-analyses. Why? It is the way they calculated their numbers. This meta-analysis, like the earlier one from the same group, reports outcomes per-cholesterol-reduction. The unit they use is a “1 mmol/L reduction in low density lipoprotein (LDL)”, in common U.S. terms, a roughly 40-point drop in LDL.

That’s the magic: each of the benefits reported in the paper refers to patients with a 40-point cholesterol drop. Voilá. One can immediately see why these numbers would look different than numbers from reviews that asked a more basic question: did people who took statins die less often than people taking a placebo? (The only important question.) Instead, they shifted the data so that their numbers corresponded precisely to patients whose cholesterol responded perfectly.
Patients whose cholesterol drops 40 points are different than others, and not just because their body had an ideal response to the drug. They may also be taking the drug more regularly, and more motivated. Or they may be exercising more, or eating right, and more health conscious than other patients. So it should be no surprise that this analysis comes up with different numbers than a simple comparison of statins versus placebo pills. Ultimately, then, this new information tells us little or nothing about the benefits someone might expect if they take a statin. Instead it tells us the average benefits among those who had a 40-point drop in LDL.

But LDL drop cannot be predicted. Some won’t drop at all, some will drop just a bit, and some may drop more. Therefore the numbers here tell an interesting story about certain patients who took statins, but they have no relevance to patients and doctors considering statins. And yet, the latter group is the target of the study's concusions.

True story: in prior meta-analyses that found no mortality benefit the investigators simply looked at studies of patients without heart disease and compared mortality between the statin groups and the placebo groups. No machinations, no acrobatics, no per-unit-cholesterol. They took a Joe Friday approach (just the facts, ma’am), and found no mortality benefit.

Perhaps never has a statistical deception been so cleverly buried, in plain sight. The study answers this question: how much did the people who responded well to the drug benefit? This is, by definition, a circular and retrospective question: revisiting old data and re-tailoring the question to arrive at a conclusion. And to be fair they may have answered an interesting, and in some ways contributory, question. However the authors’ conclusions imply that they answered a different, much bigger question. And that is not a true story.

Guideline writers, doctors, patients, journalists, and policy makers will all have to pay close attention to avoid the trappings of deceptive data, dressed up as a true story.

*The Cochrane Collaboration analysis reports an overall mortality benefit with statins (RR=0.86), however their summary suggests that statins should be used for primary prevention “with caution.” In particular on p.12, after a discussion of the biases in many of the trials that led to their numerical finding, they clearly state that using statins for patients with anything less than a 2% per year risk of coronary events “is not supported by existing evidence.” This cutoff encompasses virtually all people that would be considered candidates for primary prevention.
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Read the complete article here.

Sunday, August 3, 2014

Thousands of Women in Lipitor diabetes Lawsuit - Liebhard

Thousands of Women in Lipitor Lawsuit Claims to Join South Carolina Litigation, Status Report Shows

Published on June 16, 2014 by Sandy Liebhard 
More than a hundred cases filed by some 3,000 female Lipitor lawsuit plaintiffs will soon join the federal diabetes drug litigation in the U.S. District Court, District of South Carolina, according to court documents.

A status report recently submitted by parties involved in the federal litigation indicates that 134 cases alleging new-onset Type 2 diabetes will be transferred to the multidistrict litigation in the coming weeks, on behalf of 3,000 plaintiffs.

According to Lipitor lawsuits included in the soon-to-be transferred claims, use of the cholesterol medication, may increase a woman’s likelihood of developing Type 2 diabetes, which its manufacturer allegedly knew about but concealed from the public. Lipitor diabetes lawsuits included in the federal proceeding, which was created by the U.S. Judicial Panel on Multidistrict Litigation (JPML) less than six months ago, include similar actions against Pfizer Inc. that accuse the company of marketing a product that was designed defectively.

A Case List updated June 16th by the JPML also shows a continued increase in the number of Lipitor lawsuits filed in South Carolina federal court. An update posted that day reflects 846 cases now pending in the federal litigation, which held its most recent status conference on June 13th. A month earlier, a total of 703 claims had been filed in South Carolina.

More than 840 Claims Now Filed in Lipitor Diabetes Litigation

Lipitor is a medication approved by the U.S. Food and Drug Administration (FDA) to help lower cholesterol levels in individuals who may be at an increased risk for strokes and heart attacks.
Since entering the market in 1996, the FDA issued a mandate in February 2012 that required Pfizer to adjust Lipitor’s labeling to include its possible association with Type 2 diabetes.  This action was prompted by research published a month earlier in JAMA: Internal Medicine that found post-menopausal women at an increased risk for developing the disease. In May 2013, results of a study published in the British Medical Journal showed a 22 percent increased risk for Type 2 diabetes in patients taking atorvastatin, the generic version of Lipitor.
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Read the complete article here.

UPDATE:

Pfizer confronts surge of lawsuits over Lipitor

Fri Aug 8, 2014 1:22am EDT

Saturday, August 2, 2014

British Medical Journal acted correctly in controversy over statins

British Medical Journal acted correctly in controversy over statins

Articles containing mistaken fears over side effects of heart drugs did not need to be retracted, says independent panel
Statin pills
An independent expert panel has found that the British Medical Journal did not need to retract two articles with erroneous fears about the side-effects of statins. Photograph: Alamy
The British Medical Journal, which withdrew erroneous statements about the side-effects of statins, did not need to retract the two articles that contained them, an independent expert panel commissioned by the journal has ruled.

The panel, headed by Dr Iona Heath, former chair of the BMJ's ethics committee and of the Royal College of GPs, was asked by the editor to investigate following complaints from Professor Sir Rory Collins, co-director of Oxford University's Clinical Trial Service Unit which collates data on statins trials.

Collins called for the two articles to be retracted in their entirety, saying that they would otherwise be reprinted and mislead the public into believing statins were not as safe as the evidence shows.
After a two-month review, the panel has advised the BMJ that its handling of the two articles was appropriate and that its processes were timely and reasonable, said the journal. The panel made suggestions where improvements could be made to some of the BMJ's editorial processes and the journal will act on these recommendations, it said.

One of the articles was written by Professor John Abramson, a clinical instructor at Harvard medical school, and colleagues. The other was an opinion piece by London cardiologist, Aseem Malhotra. Both questioned the value of extending the use of statins to healthy people at low risk of heart disease and included the same incorrect statistic from a published study.

Collins and other eminent scientists say the evidence for the safety of statins, even at people with a low risk of heart attack or stroke, is very clear from the many clinical trials that have been done. They are concerned that a mistaken fear of side-effects will put people off taking drugs that could prevent heart attacks or strokes.

The BMJ has reflected the concern of many patients and GPs about the "medicalisation" of the population following a recommendation from Nice, the National Institute for Health and Care Excellence, that would lead to millions more apparently healthy people in mid-life being offered the drugs by their GP. The journal has called for all the trial data to be made public.

Collins warned that without retraction "patients and their doctors will continue to be misinformed. It seems likely, therefore, that many patients – including those at high risk of heart attacks and strokes – may well stop taking their statin therapy or will not start it, which would lead to unnecessary heart attacks and strokes".

The trials showed that around five people in every 1,000 suffered adverse events because of statins – mostly a slightly earlier diagnosis of diabetes and more rarely muscle problems. Among low risk patents, 30 to 50 per 1000 on statins would avoid heart attacks and strokes, he said.

"This has been a challenging time for the BMJ but I am very pleased the panel has taken the view that we acted appropriately," said BMJ editor in chief, Dr Fiona Godlee.

"I echo the panel's call for the individual patient data from the statins trials be made available for independent scrutiny. Patients and their doctors need access to all relevant information to make informed decisions about their health. Extending statins to healthy people is a topical issue of wide public interest and we will continue to cover the debate from all sides."
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Read the complete article here.

Friday, July 25, 2014

Niacin is/was/will always be the Good One - Penberthy


Laropiprant is the Bad One; Niacin is/was/will always be the Good One

by W. Todd Penberthy, PhD

(OMNS July 25, 2014) Niacin has been used for over 60 years in tens of thousands of patients with tremendously favorable therapeutic benefit (Carlson 2005). In the first-person NY Times best seller, "8 Weeks to a Cure for Cholesterol," the author describes his journey from being a walking heart attack time bomb to a becoming a healthy individual. He hails high-dose niacin as the one treatment that did more to correct his poor lipid profile than any other (Kowalski 2001). Many clinical studies have shown that high doses of niacin (3,000-5,000 mg plain old immediate release niacin taken in divided doses spread out over the course of a day) cause dramatic reductions in total mortality in patients that experienced previous strokes (Creider 2012). High dose niacin has also been clinically proven to provide positive transformational relief to many schizophrenics in studies involving administration of immediate release niacin in multi-thousand-milligram quantities to greater than 10,000 patients (Hoffer 1964; Osmond 1962). Most importantly, after 60 years of use the safety profile for niacin (especially immediate release niacin) remains far safer than the safest drug (Guyton 2007).

Bad Reporting

So why has the media suddenly presented the following niacin alarmist headlines in response to the most recent study in the New England Journal of Medicine?
"Niacin drug causes serious side effects, study says" - Boston Globe, 7/16/14
"Niacin safety, effectiveness questioned in new heart study" - Healthday News, 7/17/14
"Doctors say cholesterol drug risky to take" - Times Daily, 7/16/14
"Niacin risks may present health risks claim scientists" - Viral Global News, 7/17/14
"Studies reveal new niacin risks" - Drug Discovery and Development, 7/17/14
"No love for niacin" - Medpage Today, 7/17/14
"Niacin could be more harmful than helpful" - Telemanagement, 7/18/14
The truth of the matter is that the study quoted and used laropiprant (trade names: Cordaptive and Tredaptive). Laropiprant is a questionable drug and the results say next to nothing about niacin. The study compared over 25,000 patients treated with either niacin along with laropiprant, or placebo. The patients in this study had previous history of myocardial infarction, cerebrovascular disease, peripheral arterial disease, or diabetes mellitus with evidence of symptomatic coronary disease. The side effects observed in those who took the laropiprant-niacin combination were serious and included an increase in total mortality as well as significant increases in the risk for developing diabetes.
For responsible reporters, this should have raised the question of which compound, the drug laropiprant, or the vitamin niacin, is the culprit.
Such side effects have not been seen in over 10 major clinical trials of niacin involving tens of thousands of patients, not in over 60 years of regular usage of niacin in clinics across the country. However, niacin causes a warm flush on the skin. Some people find the warm niacin flush uncomfortable, although many people enjoy this temporary sensation. In this study, niacin was given in combination with laropiprant, a drug that prevents the niacin flush. By including a dose of laropiprant along with the niacin to eliminate the flush, the thought was that more patients could benefit from niacin without complaint. But in fact the niacin flush is healthy. A reduced flush response to niacin is a diagnostic for increased incidence of schizophrenia, and this assay is now widely available (Horrobin 1980; Messamore, 2003; Liu 2007; Smesny, 2007).

Problems with Laropiprant

So what about the other half of the combo, the drug laropiprant?
  • Laropiprant has never been approved by the FDA for use in the USA and when taken alone has been shown to increase gastrointestinal bleeding. *
  • Laropiprant interferes with a basic prostaglandin receptor pathway that is important for good health.
  • Last year Merck announced it would withdraw laropiprant worldwide due to complaints from continental Europe. Therefore the clinical trials in this most recent study could only be performed in the UK, Scandinavia, and China.
So why did so many media outlets and even some MDs conclude that niacin was the problem? Simple: none of the headlines mentioned laropiprant, which is quite clearly the real culprit that caused the side effects reported. The simplest way to put it is to say that sensational stories promulgated by the media are quite often completely wrong. This suggests a hidden agenda.
Confusing and fantastical headlines can increase readership for hysteria-based business models. Which headline is likely to garner the greatest attention: "Laropiprant is a Dangerous Medication that has Not Been Approved by the FDA" or "Niacin Causes Serious Side Effects"? The correct headline would be, "Niacin doesn't cause serious side effects; drugs do."

Why the B Vitamins Are So Important

The B vitamins were discovered due to terrible nutritional epidemics: pellagra (niacin/vitamin B3 deficiency) and beriberi (thiamine/vitamin B1 deficiency). We are very sensitive to a deficiency of niacin. Over 100,000 people died in the American south in the first two decades of the 20th century due to a lack of niacin in their diet. It was perhaps the worst nutritional epidemic ever observed in modern times, and was a ghastly testimony to how vulnerable the human animal is to niacin deficiency. The pellagra and beriberi epidemics took off shortly after the introduction of processed foods such as white rice and white flour. Poor diets, mental and physical stresses, and certain disease conditions have all been proven to actively deplete nicotinamide adenine dinucleotide (NAD) levels, causing patients to respond favorably to greater than average niacin dosing.
How is it possible that niacin can be useful for many different conditions? It seems too good to be true. The reason is that niacin is necessary for more biochemical reactions than any other vitamin-derived molecule: over 450 different gene-encoded enzymatic reactions (UniproKB database of the Swiss Institute of Bioinformatics; (Penberthy 2013)). That is more reactions than any other vitamin-derived co-factor! Niacin is involved in just about every major biochemical pathway. Some individuals, who have a genetically encoded amino acid polymorphism within the NAD binding domain of an enzyme protein, will have a lower binding affinity for NAD that can only be treated by administering higher amounts of niacin to make the amount of NAD required for normal health. Genetic differences such as these are why many individuals require higher amounts of niacin in order for their enzymes to function correctly (Ames 2002).
It is a deadly shame that the media so often ignores this information. Fortunately, many physicians will see through the recent headlines that give misinformation about niacin, having already personally witnessed how effective high dose niacin therapy is for preventing cardiovascular disease.

Nutrients are the Solution, Not the Problem

So what is the solution? At the end of the day the data on patients with problem cholesterol/LDL levels still support 3,000-5,000 milligrams of immediate-release niacin as the best clinically-proven approach to maintaining a healthy lipid profile. Niacin in 250mg to 1000mg doses can be purchased inexpensively from many sources. Extended-release niacin is the form of niacin that is most frequently sold by prescription, but it has more side effects than immediate release (plain old) niacin. . . and it costs much more.
Tangential to niacin but pointed to cardiovascular disease, conventional medicine is finally beginning to respect chelation therapy as an approach owing to the recent unparalleled positive clinical results for cardiovascular disease patients with diabetes - up to 50% prevention of recurrent heart attacks and 43% reduction in death rate from all causes (Avila 2014). Some times chelation therapy can be expensive. However, there are other inexpensive approaches include high dose IP6 therapy that are yet to be conventionally appreciated. Other supplements desirable for any ideal cardiovascular disease: a nutritional regimen include additional vitamin C, magnesium, coenzyme Q, fat soluble vitamins (A, D, E, and K2), and grass-fed organic butter. Your ideal intake varies with your individuality.
Nutrients such as niacin you need. Media misinformation you don't.
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Read the complete article here.

Monday, July 21, 2014

FDA Approves Dangerous and Worthless Cholesterol Drug - Brownstein

FDA Approves Dangerous and Worthless Cholesterol Drug


by Dr. David Brownstein

On May 3, 2013, the FDA approved a Big Pharma Cartel founding member Merck drug Liptruzet.  Liptruzet is a combination drug of Zetia and Lipitor.  I wrote to you about the failure of Zetia in three separate blog posts.  They can all be found by clicking here:  http://blog.drbrownstein.com/?s=zetia.
Zetia is a failed drug.  It should never be prescribed and should have been pulled from the market years ago.  There is no excuse for any doctor prescribing Zetia for any condition.  Zetia works by blocking cholesterol absorption in the gut.  Conventional doctors believe that drug therapies that lower cholesterol levels reduce the risk of heart disease.  However, Zetia, which has been around for over 10 years, has never been shown to lower the risk of developing a heart attack or stroke.  Furthermore, Zetia has never been shown to prolong life.

Why the FDA would approve this combination of Zetia and Lipitor is beyond belief.  The previous combination of Zetia and Zocor, known as Vytorin, was proven to be a colossal failure in multiple studies—see my previous blog posts.

FDA’s action is a perfect example of why we spend more money on health care than any other people on the planet.  Liptruzet will cost $5.50 per pill.  This means a patient prescribed Liptruzet will spend over $2,000.00 per year on a worthless drug that will be associated with side effects such as muscle aches and pains, memory loss, and neurological disorders.  We take too many ineffective drugs that are too expensive.  Do all of these drugs translate into better healthcare outcomes?  Heck no.  As compared to every other wealthy Western country, we finish last or near the bottom on every single health indicator.  In Liptruzet’s case, there is no justifiable reason for the FDA to approve it.  This is another example, amongst many, of why the FDA should be disbanded.  The FDA gives false credibility to Big Pharma.

If you are on Zetia, I suggest talking to your doctor about stopping it.  Ask him/her for any studies showing a clinical benefit such as a significantly lowered risk for heart disease, heart attack, stroke, or increased longevity.  I can assure you that you won’t be getting any articles from your doctor since they don’t exist.   More information about cholesterol-lowering medications can be found in my book, Drugs That Don’t Work and Natural Therapies That Do
=======================================================Read the complete article here.

Do statins prevent or promote cancer? - Current Oncology

Do statins prevent or promote cancer?

Mark R. Goldstein MD FACP, Medical Director, Fountain Medical Court, 9410 Fountain Medical Court, Suite
The Editor, Current Oncology December 24, 2007
 
In their commentary, Drs. Takahashi and Nishibori discuss putative antitumour effects of statins. However, prospective data suggest that statins actually increase cancer in certain segments of the population. Additionally, new findings regarding the immunomodulatory effects of statins may explain the mechanism by which that increase occurs.

Statins increase the number of regulatory T cells (Tregs) in vivo by inducing the transcription factor forkhead box P3. Although that increase may be beneficial in stabilizing atherosclerotic plaque by reducing the effector T-cell response within the atheroma, it might impair both the innate and adaptive host antitumour immune responses. Not surprisingly, the number of Tregs present in many solid tumours correlate inversely with patient survival.

Indeed, analysis of large randomized statin trials demonstrate a highly significant (p = 0.009) inverse association between achieved low-density lipoprotein cholesterol levels and cancer. Close inspection of statin trials reveal the specific populations at risk for the development of incident cancer with statin treatment. These include the elderly and people with a history of breast or prostate cancer,. Furthermore, statin-treated individuals undergoing immunotherapy for cancer may be at increased risk for worsening cancer.

The elderly are relatively immunosuppressed and are more likely to harbour occult cancers. In the prosper (Prospective Study of Pravastatin in the Elderly at Risk) trial, a 3.2-year prospective study of pravastatin for cardiovascular disease prevention in the elderly (mean age at trial entry: 75 years) at high risk for cardiovascular disease, cancer incidence was significantly increased in subjects randomized to pravastatin. In fact, the increase in cancer mortality equalled in magnitude the decrease in cardiovascular disease mortality in the statin-treated patients, leaving all-cause mortality unchanged. Likewise, post hoc analysis of the lipid study, a 6-year prospective trial of pravastatin in individuals with cardiovascular disease, revealed a significant increase in cancer incidence in the elderly subjects (age: 65–75 years) randomized to pravastatin. In a secondary analysis of the tnt (Treating to New Targets) study, elderly subjects randomized to high-dose atorvastatin (80 mg daily) versus low-dose atorvastatin (10 mg daily) demonstrated a trend toward increased death, largely from an increase in cancer mortality. Therefore, the increase in incident cancer in the elderly might be dose-related. It is highly plausible that the elderly are particularly sensitive to a statin-induced increase in Tregs, further impairing their immune response to cancer.

An alarming increase in breast cancer incidence, some of which were recurrences, was seen in women randomized to pravastatin in the care trial Thereafter, cancer was an exclusion criterion in randomized statin trials. In clinical practice, however, it is not infrequent to find an association between recurrence of breast cancer and concurrent statin therapy. Long-term follow-up (10 years after trial completion) of woscops (West of Scotland Coronary Prevention Study), a 5-year prospective trial of pravastatin in hypercholesterolemic men, revealed an increase in prostate cancer in the men who were randomized to pravastatin therapy. That finding indicates that cancers may become evident a decade or more after treatment with statins. Treg increases have been associated with both breast and prostate cancers,, and therefore, it is highly plausible that the increase in cancers seen with statin therapy is related to a statin-induced increase in Tregs.

Statin therapy has been associated with tumour progression leading to radical cystectomy in patients treated for bladder cancer with bacille Calmette–Guérin immunotherapy. That association may be likewise due to a statin-induced increase in Tregs, resulting in impaired host antitumour immunity.
Statin trials have typically randomized subjects free of prevalent cancers and have been about 5 years in duration. Long-term follow-up data are limited, particularly for the development of cancer. Statins are now promoted for widespread use in adults of all ages and at high doses, potentially for decades. Importantly, they are used in individuals with other significant comorbidities such as cancer. Unfortunately, the post-market surveillance of drugs has been poor. Because cancer is highly prevalent in the population, particularly in the elderly, a statin-induced increase in cancer incidence will likely go unrecognized.

Long-term prospective data are needed on the feasibility of statin therapy in the very elderly, the immuno-suppressed, and those with prevalent cancer. Furthermore, long-term outcome data are needed in young individuals treated with statins for prolonged time periods. Perhaps a constant increase in Tregs over years, even in the young, will weaken host antitumour immune surveillance and increase the risk for various cancers.

In conclusion, we feel that there is ample evidence that statins may promote cancer in certain segments of the population. Currently, the indications for statin therapy are based on lipoprotein levels, prevalent cardiovascular disease, other vascular risk factors, and family history. Maybe it is time for a new paradigm that also includes age extremes, prevalent cancer, a past history of cancer, and overall immunocompetence.

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13. Hoffmann P, Roumeguère T, Schulman C, van Velthoven R. Use of statins and outcome of bcg treatment for bladder cancer. N Engl J Med. 2006;355:2705–7. [PubMed]
14. Gruver AL, Hudson LL, Sempowski GD. Immunosenescence of ageing. J Pathol. 2007;211:144–56. [PMC free article] [PubMed]
15. Winer EP, Harris JR, Smith BL, D’Alessandro HA, Brachtel EF. Case records of the Massachusetts General Hospital. Case 32-2007. A 62-year-old woman with a second breast cancer. N Engl J Med. 2007;357:1640–8. [PubMed]
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Wednesday, July 9, 2014

Low Cholesterol Leads to an Early Death - FallonMorell

Low Cholesterol Leads to an Early Death: Evidence From 101 Scientific Papers

This book is a sequel to Cholesterol and Saturated Fat Prevent Heart Disease: Evidence from 101 Scientific Papers by the same author (and given a Thumbs Up review in Wise Traditions, Summer 2013). Evans provides studies in chronological order showing that the lower your cholesterol, the earlier you die; that high levels of both “good” and “bad” cholesterol help you to live longer; that high cholesterol does not cause cardiovascular disease; that low cholesterol leads to an early death in many diseases; and that low cholesterol leads to an increased prevalence of many diseases.
Some gems from Evans’ book: A 1992 study of over three hundred fifty thousand men, aged thirty-five to fifty-seven, followed for twelve years, found that higher cholesterol levels were associated with lower death rates; a five-year study published in 1989 found that low cholesterol increases the risk of death by at least 340 percent in elderly women; a twenty-year study published in 2001 found that those with the lowest cholesterol levels have a 35 percent increase in death rates compared to those with the highest cholesterol levels; and a 1998 study found that low cholesterol levels are associated with higher rates of many infectious diseases including hepatitis, appendicitis, digestive and liver infections, kidney and urinary tract infections, venereal disease and musculo-skeletal infections. None of these important studies got front-page billing in the media; meanwhile the anti-cholesterol juggernaut rolls on.

This book represents a great compilation of studies we never hear about and is enhanced by an amusing foreword by Tom Naughton, producer of the movie Fat Head. Thumbs up!
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This book is available here.

Monday, July 7, 2014

Merck Uses Legal Threats To Stifle Negative Advice About Zetia And Vytorin

Merck Uses Legal Threats To Stifle Negative Advice About Zetia And Vytorin In Italy


In response to repeated legal threats, a public health doctor in Italy has withdrawn advice to curtail use of a controversial drug. The drug, ezetimibe, is a key ingredient in Zetia and Vytorin, which is manufactured by Merck Merck. The cholesterol-lowering drug has been the subject of fierce controversy because it has never been shown to improve clinical outcomes. Despite the controversy, in 2013 the drugs had combined sales of more than $2.6 billion.
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Friday, July 4, 2014

How do statin proponents deal with debate? They stifle it - Briffa

How do statin proponents deal with debate? They stifle it.

Last month, one of my blog posts featured a letter written by a group of doctors, expressing their concerns about the mooted expansion of statin therapy. The letter detailed six major objections to the plan, including the mass-medicalization of millions of healthy individuals, the unreliability of the evidence regarding the adverse effects of statins, and the facts that almost all the evidence is industry-funded and that multiple conflicts of interest exist on the ‘expert committee’ that is adjudicating on the statin issue. The letter received widespread coverage in the press and other media, and I think it did much to stoke the flaming debate that some have described as the ‘statin wars’.

Those strongly supportive of the plans to widen statin prescriptions are hardly going to go away without a fight, though. And this week six professors convened a press briefing at the Science Media Centre to put forward their arguments. The briefing was reported in the British Medical Journal this week [1].

Two of the ‘usual suspects’ were Professor Sir Rory Collins (head of the Cholesterol Treatment Trialists collaboration) and Professor Peter Weissberg (medical director of the British Heart Foundation).

One of Professor Collins’ gripes was, apparently, that “misrepresenting the evidence” will have a negative impact on people who are at high risk of cardiac events. He is quoted as saying: “It’s perfectly reasonable to debate whether patients at lower risk should get statins or not, but it’s inappropriate to misrepresent the evidence.”

He redoubled his assertion that rates of ‘myopathy’ are much lower than some people state. However, he is referring to the incidence of muscle problems where the threshold of ‘abnormal’ is when levels of the enzyme used to assess muscle damage (creatinine kinase) is at least 10 times the upper limit of normal. Professor Sir Rory Collins is apparently disinterested unless muscles are in near-meltdown. We can, I suppose, just ignore those poor unfortunates with less biochemical aberrations even though their symptoms are real and often debilitating. I think it’s clearly business as usual for Rory Collins, who makes claims that some are misleading the public while I think he, ahem, continues to mislead the public.

Professor Weissberg tells us that the “…the critics are wrong. They’ve retracted, they’re wrong.” Except, that the only thing that has been retracted were the misleading representations of statin side-effects as reported in one piece of research. All the major objections detailed in the original letter stand until someone properly disputes them.

With regard to these, Professor Weissberg calms any concerns about industry involvement in the evidence base, because drug companies only paid people to do the studies, rather than the drug companies doing the studies themselves. So, nothing to concern ourselves with here.

He adds that: “The biggest threat to good medicine is prejudice and anecdote.” I have some sympathy for this view, but boy would I like to see Professor Weissberg stay away from prejudice and anecdote myself. It was not so long ago that he made claims to support statins using data that did not support the use of statins at all.

And perhaps the most telling thing of all are the comments that come from Fiona Fox, director of the Science Media Centre. Apparently, only pro-statin experts were invited to the briefing. In defence of this tactic, Ms Fox tells us that the “vast majority” of cardiac and statin experts believed that the evidence was overwhelming, and that it was not the centre’s job to provide a platform to a minority who did not and thereby project a false image that the debate was in equipoise (when it was not).
First of all, I wouldn’t be too sure that the evidence is overwhelming or that the pro-statin camp is in the great majority.  And even if there things were true, is that a reason to stifle debate and allow no right of reply?

Do these tactics suggest that Professors Collins and Weissberg and the rest of their merry band of men have true confidence in their position? I personally doubt it, and believe that their attempt to shut down debate suggests they may be desperate not to have the weakness of the data and their arguments revealed in front of their very own eyes.

References:
1. Hawkes N, et al. Six professors back NICE guidance on extending use of statins. BMJ 2014;349:g4380
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