Statins and Mortality

Dr. Neville S. Wilson. – 15 July 2007.

The widely held belief that blood cholesterol levels are potentially harmful and should be lowered in order to prevent heart disease is a product of speculative and persuasive promotion by advocates of what has been called the “cholesterol hypothesis“.

The pharmaceutical industry has supported and exploited this initiative in a highly aggressive and commercially successful marketing strategy and has received tacit support from certain factions of the food industry, who have likewise seized on this  profitable opportunity by demonizing dietary fats and promoting the so-called benefits of low cholesterol foods.

This large scale anti-cholesterol strategy has not only failed to halt the progression of cardiovascular disease but has precipitated  a  trend toward an increase in the consumption of “low-fat” foods, amounting to an increase in dietary  processed carbohydrates, and unprecedented levels of obesity, diabetes and associated morbidity on a  world-wide scale.

The medical profession has, in many cases, unwittingly reinforced this perception by its preoccupation with cholesterol figures and reduction strategies, using complex algorithms to evaluate risk and predict mortality, without giving consideration to the unique circumstances of the individual, and the relevant factors of age, gender, race, and lifestyle, which are important determinants of morbidity and mortality.

The consequences of scare-mongering tactics by the food and drug industry, and high pressure marketing strategies aimed at influencing the prescribing habits of doctors, has created a climate of cholesterol-phobia which is highly manipulative, and not in the best health interests of unsuspecting patients.

STUDIES & MORTALITY:

Collectively, the major clinical trials, involving various strengths of statin drugs in a range of diverse population groups, has not demonstrated all-cause mortality benefits for patients.

Clearly, statins have not been shown to extend lifespan, while at the same time creating  the potential for a range of serious harmful effects in patients using them to lower their cholesterol levels.

In a large clinical trial involving over 10,000 participants randomly assigned to two groups for comparison, those using very high dose statins (Lipitor 80mg.) achieved markedly lower LDL-C levels than those using a much lower dose (Pravastatin 10mg.), and also had 26 fewer deaths in their group.

However, the total number of deaths from causes other than cardiac was GREATER in the high dose group, exceeding those in the low dose group by 31.

Overall mortality was thus not decreased by the aggressive treatment with high dose statins, prompting a cautionary word from an accompanying editorial stating that “further assurances as to the safety of this approach was needed”. (NEJM 2005).

Of further concern was the fact that 85% of the non-cardiac deaths in the high dose group was due to cancer, compared to 75% in the lower dose group.

In another randomized controlled trial (IDEAL) using high and low dose statins, 90% of the participants in both groups  experienced adverse effects of which more than half were serious, yet very little mention was made of these observations by the researchers.

In a 30 year follow up of one of the longest studies ever conducted (Framingham) it was conclusively shown that patients with higher than normal cholesterol levels lived longer than those with lower levels. In fact, “for every 1 mg/dl DECREASE in cholesterol there was a 14% INCREASE in death from cardiovascular causes.  ( JAMA 1987 April 24; 257:2176–2180)

The discovery that statin drugs are able to reduce cholesterol levels in humans, despite their inability to reduce mortality, continues to attract support from self-acclaimed authorities such as the National Cholesterol Education Programme (NCEP), The National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Health (NIH).

Protests from the Centre for Science in the Public Interest to these bodies, seeking an independent and unbiased review of their established cholesterol guidelines, have been met with refusal and a dogged unwillingness to recognise the abundant data which clearly contradicts the dogma espoused by these influential bodies.

Controversy reigns as to who should be targeted for statin therapy, since collectively the statin trials have not shown any benefit in reducing OVERALL mortality.

Lowering blood levels of cholesterol with drugs like statins has not saved lives, OVERALL, and has led to continued efforts and much cost, to try and identify the benefits and /or risks of statin drugs.

BENEFITS VS RISKS:

Although benefits have been reported in select groups of individuals, such as males with histories of established heart disease, and diabetic patients, especially those with peripheral neuropathy (i.e., damage to the nervous system) the potential risks, for a variety of unwanted adverse effects, have been widely documented, and are a source for growing concerns about long term toxicity and harm that are generally underestimated by health professionals.

Some of these adverse effects may be uncommon, but others occur frequently and are often wrongly attributed to ageing or other conditions, and are thus ignored or minimized. (BMJ 2006;332:1330–1332).

In some of the major statin trials subjects who were experiencing unwanted side-effects were exluded from further continuation in the trial, a move guaranteed to produce a favourable statin result for the trial sponsors.

THE STUDIES:

In the TNT Trial, more than 3000 people .were excluded because they did not fulfil the criteria for entry because they had abnormal liver functions, cancer or other diseases, and after commencing the trial with low dose statin, a further 5429 patients were rejected for a variety of reasons, which included adverse events, or unwillingness to continue.

In total, only 54% of the originally selected 18,468 participants were permitted to enter the trial. These participants were therefore healthier than a comparative section of the community using statin drugs, and yet they failed to achieve the advantage of improved lifespan while using the same drugs.

A review of the well-known clinical trials involving statins reveals little evidence for safety and benefit in women, the elderly, children and ethnic groups.

THE RISKS:

Targeting such individuals with statin drugs, a move which appears to be gathering momentum, particularly in the UK, places them clearly at risk for potential adverse effects, and exposes clinicians to the real charge of exploiting a hypothesized interventive protocol that is not evidence based.

The UK proposal to expand screening and extend the range of prescribing statins to the general public is frightening in terms of its potential for turning healthy individuals into hypochondriacs, or at worst, into statin cripples.

Of particular concern is the potential for childbearing women, who may unwittingly receive prescriptions or OTC statins, to conceive children with malformations, not unlike those experienced during the Thalidomide scare in the 1960’s.

There is now a growing body of concerned researchers who openly challenge the “cholesterol hypothesis” on sound scientific grounds, and who have demonstrated the limited, and thus insignificant, benefits reported in the wake of the major statin trials, and who caution against the indiscriminate use of statins based on figures alone.

CHOLESTEROL PROTECTIVE:

The scientific evidence is clear, that cholesterol per se, does not damage or “block arteries”, (as is so simplistically and incorrectly stated by health columnists and advertising propaganda), and that in many cases, high levels of cholesterol can be protective, especially in post-menopausal women, and that low levels of cholesterol can be harmful.

Research has shown that LDL-Cholesterol (the so –called “bad cholesterol” ) is able to provide protection against a wide array of infective organisms, by neutralizing the toxins produced by these organisms. LDL-C binds and inactivates 90% of alfatoxin, an extremely toxic chemical produced by the ubiquitous staphylococcal bacterias, and inactivates lipopolysaccharide, another harmful bacterial toxin. (Biol. Chem.258,5899–5904,1983) and (Infect.Immun 58,2375–82,1990)

Many correlations have been shown between low plasma levels of cholesterol and infective diseases. In the MRFIT study, the risk of death due to AIDS was correlated with low levels of cholesterol, a similar finding in patients with high risk for death following post-operative infection, or victims of oedematous chronic heart failure.

Low blood levels of cholesterol have also been shown to correlate closely with neurological effects such as violent or aggressive behaviour, and even depression and suicide, according to Prof. Matthew Muldoon, at the University of Pittsburgh, Pennsylvania.

These events are not likely to be recorded in trials, and are thus unlikely to be detected and reported, but there is a large body of evidence in support of this frightening phenomenon.

The evidence is thus supportive of the view, that despite limited benefits in specific population groups , statins not only fail, in the long-term, to save lives, but may endanger lives through their deprivation of normal healthy body functions such as the manufacture of essential hormones (testosterone, oestrogen, cortisone), the production of digestive bile acids, enhancement of the immune system, the maintenance of healthy nerve myelin sheaths, and the stabilization of cellular membranes.

Statins produce their cholesterol lowering effect by blocking the mevalonate pathway in the liver, but in so-doing they also block the synthesis of other vital products such as Ubiquinone, Dolichols, and Squalene, known for their capacity to maintain efficient cellular function, healthy heart muscle and anti-cancer properties.

Interrupting these potentially life-preserving functions, as statins do, can lead to the wide array of side effects such as muscle pain and weakness (far more common than documented), nerve damage (also common and under diagnosed), dizzy spells, memory loss, pancreatitis, cancer, depression, and mood swings.(Statin Drugs Side Effects by Dr. Duane Graveline, M.D.)

HEART FAILURE ?

Furthermore, lowering blood cholesterol, may, in itself, be harmful in terms of causing heart failure, the so called “cholesterol paradox”.

A recent study reported in the Journal of American Coll. Cardiology supports earlier findings (1998) that low levels of total cholesterol and lipoproteins were associated with impaired survival in patients with heart failure.
However, contradicting these findings is a study from UCLA that heart failure patients may benefit from statin usage.

Several lines of study, nevertheless, show that heart failure can be precipitated by statins since they inhibit the synthesis of coenzyme Q10 which plays a vital role in cellular energy production, particularly in heart muscle cells.

Dr. Julian Whitaker, an authority on coenzyme Q, has warned that the increasing incidence of heart failure witnessed today is likely a consequence of the widespread use of statins and their interference with normal coenzyme Q levels in heart muscle.

STATIN BENEFIT:

Where benefits are linked to statin therapy ( as there have been ) these have been shown to be entirely independent of the cholesterol levels achieved, and are likely due to the anti-inflammatory properties of the statins in use.

Focusing on blood cholesterol levels only, and ignoring other important risk factors and risk markers, is short – sighted , irresponsible and costly, both in terms of national economic burden, and the subsequent emotional, physical, and mental health burden that unsuspecting individuals may have to bear.

LONG-TERM BENEFITS VS RISKS ?

Because statins are intended to be a lifelong treatment, any individual subjected to such intensive and continuous drug usage needs to be assured, on the basis of clear scientific evidence, that the benefits of taking such drugs outweigh the risks.

We cannot safely predict the long term adverse effects of high, or even modest, dosages of statin drugs, and lessons should be learned from the unfortunate experiences of COX-2 inhibitors and HRT therapy, and recent experimental cholesterol-lowering drugs, like Torcedrapid, which caused many unnecessary deaths.

It is the responsibility of physicians to provide patients with the true facts regarding benefit and risk, thereby enabling them to make informed decisions about their own wellness management, and to employ prescribing habits that are based on evidence rather than assumption.

Dr. Neville Wilson

Medical Suite

The Leinster Clinic

Maynooth

15 July, 2007