Skepticism about science and medicine

In search of disinterested science

Statins: Scandalous new guidelines

Posted by Henry Bauer on 2014/03/13

The evidence in the medical-science literature is quite clear. Previous entries on this blog about statins  have pointed out that there is no evidence that “high cholesterol” increases mortality [1], indeed the opposite, namely, low cholesterol increases mortality; thus no evidence that statins are beneficial, but much evidence that statins are harmful.

Contrary to the evidence, official statements and everyday medical practice recommend and prescribe statins to bring cholesterol levels ever lower. The most recent recommendation would have 33 million more Americans taking statins. Dissenting voices will no doubt be ignored just as they have been in the past.

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In November 2013, the American College of Cardiology and the American Heart Association published “2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults”.

The document illustrates quite a few of the things that are so fatally wrong with present-day medicine and science [2]:

Who actually wrote this?
The Guideline bears the stamp of approval of eminent organizations, but it is not revealed who actually developed it. Sixteen “Expert Panel Members” are listed by name as well as five “Methodology Members”, fourteen “Task Force Members”, and a couple of people forming a Subcommittee on Prevention Guidelines.
But who actually did the literature search, deciding what to include and what to leave out from the mass of published material about statins and their benefits and their side effects? In this respect the Guideline is typical of Official Reports, which are all too often self-important and self-serving emanations from august bodies: The actually responsible individuals are not named, the staff who did the work that the “experts” then lent their names to. There is no independent “peer review” of these documents. There is no obvious substantive reason why they should be regarded as authoritative, and often they are remarkably incompetent on elementary points [3].
Such documents are comparable in their lack of authenticity to the many articles in medical journals that are written by staff of drug companies but published under the names of MDs. (Such “ghost-writing” is described and documented in many of the books on my list of critiques of practices in medicine and science.)

Conflicts of interest
This Guideline is fatally flawed by conflicts of interest [4] — as is all almost all the information that comes to practicing physicians, media, public, and policy makers about prescription drugs and medical devices, because it emanates either from the drugs and devices industries or from sources that are paid by those industries in one way or another. That very much includes the Food and Drug Administration and its advisory committees.

Risk Factors
The literature is chock-a-block full of misrepresentations of data because mere correlations are called “risk factors” and then treated as though they were actual risks, which commits the elementary blunder of confusing correlation with causation.
In the case of heart disease, these risk factors include C-reactive protein, troponin, overall or LDL cholesterol. These are biomarkers, measurable quantities that are taken to be measures of cardiovascular disease although they are not [5]. Yet these measures guide the prescribing of statins and antihypertensive drugs.
The new Guideline relies on estimates of the 10-year risk of cardiovascular disease and reduces the criterion for treatment from a risk of 20% to 7.5% That would increase by 33 million the number of Americans on statin treatment [6].

Weasel-Worded Critiques
Competent insiders are fully aware that drugs are prescribed without adequate evidence of efficacy or safety [2]. But it is rare for any of them to do more than publish academic articles or technical books about it, when what is needed is for members of the profession to take responsibility for actions to make things better — as the Hippocratic Oath would demand of them.
One small illustration: John Ioannidis has published devastating analyses of the unreliability of clinical trials and other aspects of the medical-science literature, but he stops short of stating the obvious conclusions about needed action. About the new Guideline he wrote a piece [7] that makes quite clear to any discerning reader that the Guideline is a catastrophe waiting to be put into practice, yet he soft-pedals his own text by writing, “It is uncertain whether this would be one of the greatest achievements or one of the worst disasters of medical history” instead of stating plainly what his analysis clearly shows, namely, that “this would be one of the worst disasters of medical history”.
The Guideline promotes itself as an improvement. In explaining what the improvement is it reveals, no doubt unwittingly, that the officially practices unreservedly recommended up to now have been quite unjustified: “Treat to target — This strategy has been the most widely used the past 15 years but there are 3 problems with this approach. First, current clinical trial data do not indicate what the target should be. Second, we do not know the magnitude of additional ASCVD risk reduction that would be achieved with one target lower than another. Third, it does not take into account potential adverse effects from multidrug therapy that might be needed to achieve a specific goal” (p. 17). In other words:

It isn’t known what level of cholesterol might be desirable,
and the severity of possible side effects is also not known —
yet despite that, for decades doctors have been prescribing statins
to bring cholesterol to increasingly lower levels.
This might reasonably be described as non-evidence-based medicine
or perhaps systematic malpractice.

Swamping substance with detail
The published Guideline runs to 84 pages. The mind-numbing details serve to distract from the most significant points.
Estimates of risk and benefit are based on invalid measures, namely, biomarkers instead of patient morbidity and mortality, and important assumptions are not stated. For example, “Some worry that a person aged 70 years without other risk factors will receive statin treatment on the basis of age alone. The estimated 10-year risk is still ≥7.5%, a risk threshold for which a reduction in ASCVD risk events has been demonstrated in RCTs [randomized Clinical Trials]. Most ASCVD events occur after age 70 years, giving individuals >70 years of age the greatest potential for absolute risk reduction” (p. 18).
But there are no actual data about the end results of treatment of people aged >70 because clinical trials do not enroll individuals of that age. As a number of critics have noted, older people are typically prescribed half-a-dozen or more medications, yet there are no data on interactions of those medications or possible synergy of their “side” effects.
Observational studies, however, indicate that cholesterol lower than 180 (mg/dL = 4.65 mmol/L) is associated with significantly higher mortality [8]. Kauffman [9] cites other sources that report similar observations.

Mutually contradicting statements are not acknowledged or explained
“By more accurately identifying higher risk individuals for statin therapy, the Guideline focuses statin therapy on those most likely to benefit” (p. 18) makes it seem as though prescribing is to be more focused, implying more restricted prescribing — whereas the effect would be the opposite, increasing statin prescribing very significantly. The Guideline is quite clearly less focused by decreasing the risk criterion from 20% to 7.5% (i.e., less risk of heart disease).
“The statin RCTs provide the most extensive evidence” (p. 16) — whereas “only 1 approach has been evaluated in multiple RCTs — the use of fixed doses of cholesterol-lowering drugs” (p. 9).
In fact, there is a “lack of data on the long-term follow-up of RCTs >15 years, the safety and ASCVD event reduction when statins are used for periods >10 years” (p. 17): yet most people are prescribed statins for life, which often means significantly longer periods than 10 or 15 years.
It is not even known what lowering cholesterol does in people who actually have atherosclerotic disease: “no data were identified regarding treatment or titration to a specific LDL–C goal in adults with clinical ASCVD” (p. 20).
As cited above, the Guidelines acknowledge that it isn’t known what levels of cholesterol might be desirable; yet the Risk Calculator  concludes with recommendations for prescribing statins to lower cholesterol.
However, for me (age 82), the recommendation read:

“Not In Statin Benefit Group Due To Age > 75 Years
Before initiating statin therapy, it is reasonable for clinicians and patients
to engage in a discussion which considers the potential
for ASCVD risk reduction benefits and for adverse effects,
for drug-drug interactions, and patient preferences for treatment.”

In other words, there is no evidence that statins are of benefit to people aged >75, yet we are encouraged to discuss with our doctors, whether or not to take these drugs of no proven benefit that also carry significant risks of harm. What about “First, do no harm”?

On the other hand, Googling “cardiac risk calculator” might take you to the Pooled Cohort Risk Assessment Equations  (also said to be based on the new Guideline) which do not hesitate to assign me a 44.2% 10-year risk, compared to only 24% for “a similar patient with optimal risk factors” which are said to include total cholesterol of 170 or less (mine is 131), HDL of 50 (mine is 35), not diabetic (I’m not), not a smoker (I haven’t been for 22 years, and smoked <5 cigarettes a day for a decade before that) and not taking medications for hypertension (I don’t) with systolic blood pressure (BP) of 110 (mine is typically 165 or less when not too active or stressed). BP increases normally with age, and published data give an average of 153 for my age of 82 [10], so claiming 110 as “optimal” is something of a flight of fancy. Admittedly, the calculator warns that the result of 44.2% may be “less accurate” because it substituted its maximum age of 79 for the actual 82.
My jaundiced view of all this is not lessened by the absurdity of “44.2” for this sort of estimate: any competent individual would not allow numbers like that to be presented instead of “about 45” or even better “a bit less than 50”, given all the assumptions and uncertainties built into the calculation.
Given that the Risk Calculator’s whole purpose is to guide administration of cholesterol-lowering statins, it seems incongruous to read that “The panel makes no recommendations for or against specific LDL–C or non-HDL–C targets for the primary or secondary prevention of ASCVD” (p. 22, Table 4).

Experts, who they are, and what their role should be in making policy
Almost all the signatories to the new Guideline are MDs. But the significant expertise here is the understanding of published results whose validity depends on proper experimental or observational protocols and proper application of statistics. The Guideline would deserve more respect if it had been developed by biostatisticians with no connection to drug companies and without other conflicts of interest.
It is worth remembering that, as George Bernard Shaw wrote, “all professions are a conspiracy against the laity”; and just as war is too important to be left to the generals, so policies about medicine and science are too important to be left to the practitioners in those fields: they should be listened to, cross-examined, disbarred for conflicts of interest, but they should not be allowed to decide on public policies and issue recommendations.

A few sane voices
The Guideline was immediately and properly criticized by a few insiders and observers: “statins have no overall health benefit in this population [risk criterion of 7.5%] . . . . [because] “Lifestyle factors — including lack of exercise, tobacco use, and unhealthy diet — account for 80% of cardiovascular disease . . . . [and] side effects of statins — including muscle symptoms, increased risk of diabetes (especially in women), liver inflammation, cataracts, decreased energy, sexual dysfunction, and exertional fatigue — occur in about 20% of people” [11]; “2% of individuals treated with statins will develop diabetes and 10% will have muscle damage”, and that harm is not balanced by the estimated benefits — “98% will see no benefit; 1.6% will be spared a heart attack and 0.4% a stroke—and importantly, there will be no difference in overall mortality” [4; emphasis added].
The Risk Calculator overestimates by 75-150%. “Barbara Roberts, a cardiologist . . ., said that the new guidelines are a “big kiss to big Pharma. . . . According to the new risk calculator all African American men aged 65 and up with normal blood pressure and normal cholesterol levels
should be on statins. That’s an outrage and is unsupported by clinical evidence” [4].

Unfortunately, if history is any guide, the voices of evidence and sanity will be ignored.

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[1] In addition to the entries on my blog: “plasma total cholesterol levels poorly discriminate risk for coronary heart disease: 35 percent of CHD occurs among individuals with below-average levels of total cholesterol” — p. 143 in reference [3]
[2] Critiques of contemporary science and medicine
[3] “Official reports are not scientific publications”: chapter 8, pp. 196-213 in Dogmatism in Science and Medicine: How Dominant Theories Monopolize Research and Stifle the Search for Truth, McFarland 2012
[4] Jeanne Lenzer, “Majority of panelists on controversial new cholesterol guideline have current or recent ties to drug manufacturers”, British Medical Journal, 347 (2013) f6989 doi: 10.1136/bmj.f6989
[5] Evaluation of Biomarkers and Surrogate Endpoints in Chronic Disease, Institute of Medicine, 2010
[6] “Statins: new US guideline sparks controversy”, The Lancet, 382 (2013) 1680
[7] John P. A. Ioannidis, More than a billion people taking statins? Potential implications of the new cardiovascular guidelines, JAMA, 311 (2014) 463-4
[8] Schatz et al., “Cholesterol and all-cause mortality in elderly people . . .”, Lancet, 358 (2001) 351-5
[9] Joel M. Kauffman Malignant Medical Myths: Why medical treatment causes 200,000 deaths in the USA each year, and how to protect yourself. Infinity Publishing, 2006; ISBN 0-7414-2909-8
[10] “Hypertension”: An illness that isn’t illness
[11] Abramson et al., “Should people at low risk of cardiovascular disease take a statin?”, British Medical Journal, 347 (2013) f6123 doi: 10.1136/bmj.f6123

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