Statin cheerleaders still chanting a load of one-sided, misleading garbage.

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http://www.theomnivore.com/Lancet_statin_meta_2005.html

 

Statin Meta-Analysis Fails To Tell Full Story

 

Statin cheerleaders still chanting a load of one-sided, misleading

garbage.

 

By Anthony Colpo,

October 14, 2005

 

On September 27, 2005, the medical journal Lancet published a

meta-analysis of the data from fourteen randomized statin drug

trials(1). The results of this meta-analysis were widely acclaimed in

the media as further proof of the value of statin drugs and LDL

cholesterol-lowering.

 

For those unfamiliar with the meta-analysis concept, it involves

pooling data from various studies and calculating overall figures for

various end points. In the case of the Lancet meta-analysis, the

endpoints sought included the relative risk reductions for all-cause

mortality, coronary mortality, non-vascular mortality, myocardial

infarction, need for coronary revascularisation, and stroke. The

authors also calculated the overall incidence of cancer and

rhabdomyolysis (a well-known statin drug side-effect), and attempted

to ascertain the relationship of LDL cholesterol lowering to the

reductions in clinical endpoints.

 

The meta-analysis was conducted by a group of British and Australian

researchers calling themselves the " Cholesterol Treatment Trialists'

(CTT) Collaborators " . The financial disclosure at the end of the

Lancet meta-analysis reveals that five of the eleven authors have

received financial remuneration from manufacturers of statin drugs

tested in the analyzed trials.

 

Meta-Analysis or Mega-Nonsense?

 

A properly performed meta-analysis can be a valuable and time-saving

tool for researchers, but only when conducted in the correct manner.

 

One essential characteristic of a properly performed meta-analysis is

that it compares apples with apples, not apples with oranges. Pooling

the results from trials of a particular drug that has been shown to

exert starkly contrasting effects in different patient groups, then

presenting these results as if they apply to all patient groups, is an

extremely shady method of meta-analysis. Unfortunately, that is the

exact manner in which many meta-analyses are performed.

 

In the case of the Lancet statin meta-analysis, the researchers pooled

the results of trials involving middle aged-males with existing heart

disease, diabetics, women, and the elderly. Anyone who has

scrupulously studied the results of all the major statin trials to

date will know that statins have only been shown to reduce the

incidence of the most important endpoint of all--overall mortality--in

middle aged-males with existing heart disease and diabetics.

 

In the study summary, however, the authors merely write: " There was a

12% proportional reduction in all-cause mortality per mmol/L reduction

in LDL cholesterol…Statin therapy can safely reduce the 5-year

incidence of major coronary events, coronary revascularisation, and

stroke by about one fifth per mmol/L reduction in LDL cholesterol,

largely irrespective of the initial lipid profile or other presenting

characteristics. "

 

The authors should have emphasized, in a clear and concise manner,

that the reduction in overall mortality observed in clinical trials

ONLY applies to two clearly defined patient subgroups: middle

aged-males with existing heart disease and diabetics. But they didn't.

 

Regrettably, the study abstract (along with highly misleading media

reports based on carefully crafted press releases issued by study

authors and their drug company editors/ghost-writers) is typically the

only portion of a research paper that most so-called professionals

will ever read. Far fewer carefully read the study in full, and even

fewer will track down the studies cited in the meta-analysis and

analyze the original data for themselves. As such, most folks reading

the Lancet study summary, and the media reports compiled by gullible

and clueless journalists who wouldn't know the first thing about how

to properly analyze clinical research findings, will conclude that a

12% reduction in mortality applies to the majority of statin users.

 

As for the widely-quoted conclusion from the study that statin-induced

reductions in mortality and coronary events are directly related to

the degree of LDL cholesterol-lowering, this is a complete and utter

fallacy, one that I recently debunked at length in a

thoroughly-referenced article published in the Journal of American

Physicians and Surgeons(2) (the FREE full text of this peer-reviewed

paper can be accessed simply by clicking here).

 

If you look at the actual results of the original statin drug trials,

you will see that most of them show a complete disconnect between LDL

levels, or the degree of total or LDL cholesterol reduction, and

mortality outcomes. In fact, the PROSPER trial observed the highest

survival rates among those with highest LDL levels, a point that drug

company-sponsored researchers and health authorities seem very

reluctant to mention.

 

Unlike our current crop of drug-company owned, pro-statin researchers,

I don't expect you to merely take my word on blind faith. Below are

some studies that can be accessed online; please click on the

hyper-linked study title, then when the study appears on your screen

simply scroll down to the listed table to see for yourself the

disconnect between LDL cholesterol and mortality outcomes in large

statin trials:

 

West of Scotland Coronary Prevention Study (WOSCOPS)

See Table 2, and related commentary: " The full benefit in terms of

reduction in risk of a cardiovascular event was seen in patients in

quintile 3, who had a mean 24% decrease in LDL. No further significant

decrement in risk was apparent in those in quintile 5, who experienced

a mean 39% LDL decrease (range, 34% to 57% decrease). "

 

See also Figure 3, and related commentary: " Pravastatin treatment was

associated with a 36% (CI, 9% to 56%) lower risk (P=.014, Fig 3), a

finding that did not appear to be due to an imbalance in baseline risk

factors or to differences in on-treatment LDL "

 

Pravastatin in elderly individuals at risk of vascular disease (PROSPER)

See Table 3, which shows event rate in both treatment and placebo

groups was actually slightly lower in those with the highest LDL levels.

 

Cholesterol and, for Recurrent Events Trial (CARE)

See Table 2 and Figure 3, and related commentary: " The patients with

base-line LDL cholesterol levels above 150 mg per deciliter (3.9 mmol

per liter; n = 953) had a 35 percent reduction in major coronary

events, as compared with a 26 percent reduction in those with

base-line levels of 125 to 150 mg per deciliter (3.2 to 3.9 mmol per

liter; n = 2355) and a 3 percent increase in those with base-line

levels below 125 mg per deciliter. "

 

The CARE trial found greater risk reductions in the highest category

of LDL cholesterol, and lower risk reductions in the next lowest

category, something that would be expected if higher levels of LDL

cholesterol were dangerous. However, a small increased risk of

coronary events was seen with LDL reductions among those in the lowest

LDL category, strongly contradicting the reigning " lower is better "

mentality.

 

In the Long-Term Intervention with Pravastatin in Ischaemic Disease

(LIPID) study, (see Table 4) however, the risk of death from CHD and

nonfatal myocardial infarction was similar regardless of cholesterol

level. The pooled results of the Lancet meta-analysis came to a

similar conclusion: " …the proportional reduction in the event rate per

mmol/L reduction in LDL cholesterol was largely independent of the

presenting level. That is, the results of the present analyses

indicate that while lowering LDL cholesterol from 4 mmol/L to 3 mmol/L

reduces the risk of vascular events by about 23%, lowering LDL

cholesterol from 3 mmol/L to 2 mmol/L also reduces (residual) risk by

about 23%. "

 

If higher LDL/total cholesterol levels were so dangerous, one would

expect that reductions from these higher levels would result in

greater risk reductions. But in many of the statin studies, they

don't. This supports the theme of my JPANDS paper, which explains why

LDL cholesterol doesn't have a damn thing to do with heart disease.

The reductions in coronary mortality seen with statin drugs are due to

their well-documented anti-inflammatory, anti-clotting and antioxidant

effects. In the rare instances that greater LDL reductions via higher

statin dosages have indeed been associated with greater reductions in

clinical endpoints, all the evidence indicates that amplification of

statins' pleiotropic effects is the responsible factor. How much space

did the authors of the Lancet meta-analysis devote to serious

discussion of the role of statins' pleiotropic factors?

 

None.

 

I strongly urge anyone who has been swayed by the Lancet meta-analysis

to consult my thoroughly referenced JPANDS paper. Rather than relying

on clever mathematical maneuvers to produce highly questionable

conclusions, I have carefully dissected almost every possible argument

used in favor of the LDL hypothesis, supporting my case with relevant

experimental data in each and every instance. Among numerous other

facts, you will learn how statin drugs have been shown to exert

beneficial cardiovascular effects even when their cholesterol-lowering

capabilities are disabled!

 

So much for the LDL theory…

 

Statins: Safe as Apple Pie?

 

After reading the Lancet meta-analysis, as with most other pro-statin

hoopla, one could be forgiven for concluding that statins are

wonderfully safe agents with an extremely low incidence of adverse

side effects.

 

The authors cite an alleged miniscule increase in rhabdomyolysis risk

from statin use (rhabdomyolysis is a well documented side effect of

statin use characterized by severe muscle damage. This once-rare

disorder occurs when a large number of skeletal muscle cells die):

 

" Further evidence of the safety of the statin regimens studied is also

provided by the extremely low incidence of rhabdomyolysis (5 year

excess: 0·01%...). "

 

Drug company-sponsored researchers and health authorities are

extremely fond of citing such low incidences of adverse events in

clinical trials as proof of the safety of statin drugs.

 

As I have stated repeatedly on this site, the clinical trial

experience with statins is next to useless when assessing the safety

of statins among the general population.

 

Why?

 

Because when researchers recruit participants for statin clinical

trials, they carefully screen for--and exclude--a wide range of

individuals including women of childbearing age, those with a history

of drug or alcohol abuse, poor mental function, heart failure,

arrhythmia, and other cardiac conditions, liver and kidney disorders,

cancer, " other serious diseases " , and " hypersensitivity " to statins.

Thus, the disparity between the widespread 'real-world' prevalence of

side effects from statin use and the low prevalence of side effects in

clinical trials is hardly surprising. These trials exclude groups that

comprise a significant proportion of the real world population, and

can hardly be taken as a realistic barometer for the expected

incidence of side effects in the general population.

 

This sort of careful screening is par for the course with clinical

trials, so it's little wonder that fifty-one percent of prescription

drugs are subsequently found to have serious adverse effects not

detected prior to regulatory approval!(3)

 

And even with these strict exclusion criteria, there is evidence to

show that the clinical experience with statins has been far from

trouble-free. Data from the largest statin trial, the Heart Protection

Study (HPS), suggest that the daily 40mg dose of simvastatin used was

nowhere near as well tolerated as the authors would have us believe. A

substantial number of patients did not enter the trial after a six

week run-in before randomization; of the 63,603 potential trial

participants who entered the original screening, only 32,145 proceeded

to the run-in phase. Of these, 11,609 patients--over one

third--dropped out before the official start of the trial.

 

Of these 11,609 patients who did not proceed to the trial, sixty-five

percent " chose not to continue " for reasons that were not specified,

seventeen percent " did not seem likely to be compliant long-term " ,

thirteen percent " were considered by their own doctor to have a clear

indication for (or contraindication to) statin therapy after review of

the screening lipid results provided " , ten percent " had abnormal

screening blood results " , nine percent " reported problems associated

with the run-in treatment " (which comprised 40mg simvastatin, and

vitamins E, C, and beta-carotene), and one percent had " other reasons

for not continuing " (4). These figures suggest that the incidence of

adverse reactions to simvastatin among those who did not enter the HPS

trial ran into the thousands, a stark contrast to the handful of

adverse reactions reported among the fastidiously-screened patients

who participated in the official trial.

 

Perhaps the most lucid demonstration of the stark divide between

clinical research and 'real-life' statin side effect rates was

provided by the PRINCESS study. This study was scheduled to enroll

3,605 heart attack patients who were to be randomized to either Baycol

or placebo for three months. The trial was supposed to have had a

two-year follow-up, but the trial was stopped when cerivastatin

(Baycol) was pulled from the market in 2001. After ending the trial

early, the researchers tallied the data acquired after 4.5 months and

found little evidence of increased myopathy or rhabdomyolysis risk,

with adverse events similar in the Baycol and placebo groups(5).

 

Sounds great, but anyone familiar with Baycol will know that it was

unceremoniously yanked off the market after at least fifty-two deaths

had been linked to the drug. Baycol was causing severe rhabdomyolysis,

releasing massive amounts of muscle protein into the bloodstream. This

muscle protein saturated victims' kidneys, effectively overwhelming

their filtration capacities. Indeed, kidney failure was reportedly a

major cause of death amongst the Baycol victims. At last count, over

one hundred deaths and 1,600 injuries had been linked to Baycol. Bayer

has reportedly paid 477 million dollars to settle over 1,300 Baycol

cases out of court in the U.S., and still faces around 11,000 cases

for which the company has refused to acknowledge legal liability(6).

 

If clinical data was relied upon to ascertain the risk profile of

Baycol, one would quickly conclude that it was a remarkably safe drug

conferring no increased risk of rhabdomyolysis. Contrast these benign

findings with the real world experience, where Baycol quickly proved

itself to be a deadly menace!

 

If the most toxic statin drug in history failed to reveal its true

colors in the tightly-controlled clinical setting, what reason is

there to expect that other statin drugs will?

 

Before discarding the topic of rhabdomyolysis, the authors do offer

the following caution:

 

" However, none of the trials in the meta-analysis involved a high-dose

statin regimen and, since the risk of myopathy is dose-dependent, the

possibility that higher doses would result in clinically relevant

adverse effects cannot be excluded. "

 

This of course, has done little to stop our ever-so-responsible health

officials from gleefully jumping on the " more is better " bandwagon

when it comes to high-dose statin therapy for LDL reduction. Higher

statin drug dosages, and their subsequently greater LDL reductions are

indeed better--for profit-hungry drug companies and their shareholders!

 

Liver toxicity

 

The authors state that " Information on episodes of raised liver

enzymes was not sought for the meta-analysis… " , but concerns of liver

toxicity were dismissed simply by referring to a 2002 paper by

Tolman(7). I have already discussed the questionable conclusions of

the Tolman paper here.

 

Cancer

 

On the subject of cancer, the authors write:

 

" … an apparent excess risk of cancer with statin therapy among people

aged older than 70 years in another contributing trial was not

confirmed by the findings in the other trials. "

 

No kidding; all the other trials were dominated by younger subjects.

The aging bodies of elderly folks may serve as a far more sensitive

barometer of the carcinogenic potential of statins, especially in

short-term studies. As stated earlier, it's important to compare

apples with apples...

 

" Have We Got a Cholesterol-Lowering Deal For You! "

 

Most of us, when dealing with car salespeople or real estate agents,

take for granted that they will often greatly embellish the good

points of the product they are trying to sell, and greatly downplay or

even omit to mention any faults or flaws in that product. For better

or for worse, such behavior is par for the course in the sales arena.

When it comes to human health, nothing less than an unwavering

commitment to a full and impartial presentation of the facts should

even begin to be considered acceptable. Unfortunately, modern day

statin cheerleaders, masquerading as serious scientists, have acquired

all the characteristics of used car salesmen; they enthusiastically

expound upon beneficial clinical findings, downplay and even ignore

the serious downsides of statins, and completely neglect to emphasize

the important fact that clinical trials have shown lowered overall

mortality only in middle-aged males with existing heart disease and in

diabetics.

 

 

Shonky salesman--or drug company-funded researcher? It's hard to tell

the difference these days...

It should be pointed out that the authors of the Lancet statin

meta-analysis have not made any blatantly false claims or lied about

any of their findings. They have, however, completely 'forgotten' to

include extremely important qualifications about the suitability--or

complete lack thereof--of statins for certain patient groups. They

have also 'forgotten' to mention that real life experience with

statins indicates a far higher incidence of side effects than that

seen in clinical trials. Furthermore, they have inexplicably

'forgotten' to mention that any statistical relationship between LDL

reduction and reduced clinical outcomes is in no way proof of a causal

relationship, that statins in fact possess numerous pleiotropic

actions and that these pleiotropic effects could easily explain any

cardiovascular benefit.

 

Maybe they're just suffering from statin-induced memory loss, another

documented side-effect of these drugs(8,9) …

 

Conclusion

 

The fact remains that individuals free of heart disease, females, and

the elderly have NOT been shown to enjoy any overall mortality benefit

from statins whatsoever. No so-called 'responsible' commentator should

recommend these drugs to such groups, especially when far less toxic

natural cardio-protective strategies (exercise, low-glycemic load and

antioxidant-rich diets, omega-3 supplementation, etc) are readily

available. The publication of carefully-worded, selectively-presented

research does not excuse such behavior, but merely represents further

damning evidence that our health care system is largely a corrupt, Big

Pharma-dominated sham.

 

References

 

1. Cholesterol Treatment Trialists' (CTT) Collaborators. Efficacy and

safety of cholesterol-lowering treatment: prospective meta-analysis of

data from 90 056 participants in 14 randomised trials of statins.

Lancet, Published online September 27, 2005

DOI:10.1016/S0140-6736(05)67394-1

 

2. Colpo A. LDL Cholesterol: " Bad " Cholesterol, or Bad Science?

Journal of American Physicians and Surgeons, Fall 2005; 10 (3): 83-89.

 

3. Cohen JS. Over Dose: The Case Against the Drug Companies:

Prescription Drugs, Side Effects, and Your Health. Penguin USA. 2001.

 

4. MRC/BHF Heart Protection Study Collaborative Group. Heart

protection study of cholesterol lowering therapy and antioxidant

vitamin supplementation in a wide range of patients at increased risk

of coronary heart disease death: early safety and efficacy experience.

European Heart Journal, 1999; 20: 7254.

 

5. Hughes S. PRINCESS supports early use of statins after MI.

TheHeart.org, Aug. 31, 2004.

 

6. Pulled drug may be linked to 52 deaths. USA Today, Aug. 13, 2001

(http://www.usatoday.com/news/health/2001-08-13-cholesterol-drug.htm),

and:

1 Stop Baycol Lawyer web site (http://www.1-stop-baycol-lawyer.com/).

 

7. Tolman KG. The liver and lovastatin. American Journal of

Cardiology, 2002; 89: 1374-1380.

 

8. Wagstaff LR, et al. Statin-Associated Memory Loss: Analysis of 60

Case Reports and Review of the Literature. Pharmacotherapy, 2003; 23

(7): 871-880.

 

9. Graveline D. Statin Drugs - Side Effects and the Misguided War on

Cholesterol. This highly-recommended book features an extensive

discussion of the cognitive side effects of statin drugs. Available

from www.spacedoc.net

 

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