An editorial by Cleveland Clinic cardiologist Steven Nissen (above image) appeared in the Annals of Internal Medicine this week lamenting the problem of “Statin Denialism” on the Internet.(1-2)
Dr Steve Nissen’s editorial reveals the Mom and Pop bloggers operating out of their basements have convinced millions of American to stop taking their statin drugs. I suggest this is not the “Real Problem”. The real problem is “Statin Drug Denialists” lurking in the academic medical community, and publishing their “Statin Denialism” articles in the mainstream medical literature. Above two images of Steven E Nissen MD courtesy of New York Times and Cleveland Clinic.
Statin Denialists in the academic cardiology community such as Dr Edward Gill Professor of Cardiology at University of Colorado actually have DENIED that statin drugs have any benefit for reducing calcium score.
I just can’t believe that!
Dr Gill states:
“five randomized controlled trials have demonstrated that not only does statin treatment not reduce coronary calcium, but in fact, the progression of coronary calcium by CT scanning is indistinguishable from placebo treatment.” (Curr Atheroscler Rep. 2010 Mar;12(2):83-7.).
Another denialist is William R Ware, PhD, Emeritus Professor University of Western Ontario Canada, who wrote in 2009 that modern imaging studies have falsified the cholesterol theory of atherosclerosis. Dr Ware says:
“Contrary to the conventional wisdom, total cholesterol (TC) and LDL cholesterol in asymptomatic individuals are not associated with either the extent or progression of coronary plaque, as quantified either by electron beam tomography (EBT) or coronary CT angiography” (Med Hypotheses. 2009 Oct;73(4):596-600.)
Dr Ware also says this data has been largely ignored by mainstream cardiology. He says,
“The evidence falsifying the hypothesis that LDL drives atherosclerosis has been largely ignored.”
Autopsy Studies Do Not Correlate
Another inconvenient fact, as Dr William Ware points out in his articles, multiple autopsy studies show no correlation between serum cholesterol and the amount of coronary atherosclerosis present at autopsy.(18-20)
Statins Stimulate Atherosclerosis and Heart Failure
Another Statin Denialist is Professor of Biochemistry Harumi Okuyama of Nagoya City University, Japan who published this 2015 article in the mainstream medical literature saying that rather than prevent atherosclerosis, statins stimulate it.(22) In addition, here is what Dr Harumi Okuyama had to say about statin drugs:
“No significant beneficial effects of statins for the reduction of CVD (cardiovascular disease) mortality have been reported since 2004/2005.”(25)
Note: 2005 is when congress tightened reporting rules on drug trials.
Another Statin Denialist is Dr Mikael Rabaeus, a Cardiologist in Geneva Switzerland who published his article in the medical literature in 2017 . He actually says statin discontinuation could SAVE LIVES ! (21)
“Statin discontinuation does not lead to increased IHD (Ischemic Heart Disease) and overall mortality, at least in the months following interruption of treatment. On the contrary, one might even conclude that statin discontinuation could save lives….. In summary, it cannot be considered as evidence based to continue to claim that statin discontinuation increases mortality or that statin therapy saves lives.”(21) Quote Dr Mikael Rabaeus.
These denialists are not mom and pop bloggers on the internet. These Statin Denialists are in the mainstream medical literature!!!
More Statin Denialism articles in the mainstream medical literature:
Heart Attack Victims Have Low Cholesterol
If cholesterol was truly the cause of heart attacks, then one would expect heart attack victims to reveal the high cholesterol causing their heart attack. They found the opposite. Heart attack victims have low cholesterol. A study analyzed 137,000 heart attack patients from 541 US hospitals and found mean cholesterol was only 174. This is low, not high. (10)
Henry Ford Hospital
In addition, if high cholesterol was truly the cause of heart attacks, one would expect heart attack victims with the highest cholesterol to have the worst prognosis, and lowest cholesterol to have the best prognosis. They don’t. A study from Henry Ford Hospital in Detroit showed that three years after a heart attack, the patients with lowest cholesterol had the highest mortality (14% vs. 7 %) (10).
Laughing All the Way to the Bank
Left image : Doctor Receiving Financial Stipends, Research awards, speaking fees etc from statin drug makers: Courtesy of the best you magazine
Laughing all the way to the bank
A dozen studies show low cholesterol in the elderly is a marker for increased mortality, not improved survival.(11)
Selected Medical Conditions – Lower Cholesterol Increases Mortality
Also, in selected medical conditions such as congestive heart failure, haemodialysis, chronic obstructive pulmonary disease (COPD), as in the elderly, higher cholesterol is associated with improved survival, and lower cholesterol with increased mortality.(10)
No Mortality Benefit in Primary Prevention Setting
Another statin denialist from Cambridge, Dr Kausik K. Ray, MD published his article in 2010 concluding that men with elevated cholesterol and no history of heart disease had no mortality benefit from taking a statin drug.(13) Dr Ray says:
“Data were combined from 11 studies …on 65,229 participants followed for approximately 244,000 person-years, during which 2793 deaths occurred. The use of statins in this high-risk primary prevention setting was not associated with a statistically significant reduction in the risk of all-cause mortality.”
“Pleiotropic Effects” – Anti-Inflammatory Effects of Statins –
The two studies on this statin drug benefit for cardiac bypass by Curtis and Barakat refer to the anti-inflammatory “pleiotropic effects” of statin drugs. Cardiac bypass is associated with massive release of proinflammatory cytokines and intense systemic inflammatory response.(12) Statin drugs can help with all this inflammation by down regulating Nuclear Factor Kappa Beta (NF-κ B), the master controller of the inflammatory response. So, yes, there is a potential benefit for Statins as anti-inflammatory agents. Statin drugs block the inflammatory cytokine release in the post operative patient, thus reducing mortality from the procedure. Surprising, the authors comment that there was no proven reduction in myocardial infarction post cardiac bypass with statin drug use. This was a disappointment. The reduction in mortality was thought to be due to reduction in systemic inflammatory response. There was another benefit with reduction in episodes of atrial fibrillation. It appears that the benefit of statin drugs in this population is not as cholesterol lowering agents. The benefits are due to anti-inflammatory properties of statins. If so, then one might consider other anti-inflammatory interventions which down regulate NFkB. (12)
U-Shaped Mortality Curve
Left Image: J-Lit Mortality Data Chart courtesy Eddie Vos, Highest mortality (6%) on statins is seen at lowest cholesterol vales of 160 and below. Lowest mortality seen at total cholesterol of 250. Above 250, mortality increases. from Matsuzaki, Masunori, et al. “Large Scale Cohort Study of the Relationship Between Serum Cholesterol Concentration and Coronary Events With Low-Dose Simvastatin Therapy in Japanese Patients With Hypercholesterolemia. Primary Prevention Cohort Study of the Japan Lipid Intervention Trial (J-LIT).” Circulation journal 66.12 (2002): 1087-1095. J_Lit_Circ_2002_MABUCHI
Eddie Vos Chart Shows No Mortality Benefit in Primary Prevention
The reality is that there is no mortality benefit from lowering cholesterol with statin drugs: Both lines on the mortality chart (left) are superimposed meaning the number of deaths in the statin drug group was identical to the number of deaths in the placebo group. Left chart image: Courtesy of Eddie Vos
Analyzing data from five statin drug studies (4S, WOSCOPS, CARE, TEXCAPS/AFCAPS and LIPID), Peter R Jackson found a 1% increase in mortality after 10 years on statin drugs in people with no pre-existing heart disease (primary prevention) (Br J Clin Pharmacol. 2001 Oct; 52(4): 439–446.).
Another statin denialist is Rita Redberg, MD who bluntly says in JAMA 2012 that healthy men should not take statins. (14) Left image courtesy of Rita redberg, M.D.
Diamond and Ravnskov
Drs David Diamond and Uffe Ravnskov explain how “statistical deception created the appearance that statins are safe and effective in primary and secondary prevention of cardiovascular disease.” published in 2015 Expert Review of clinical pharmacology.(23) Their “opinion is that although statins are effective at reducing cholesterol levels, they have failed to substantially improve cardiovascular outcomes.“(23)
Who Benefits from Statin Drugs ?
Statin drugs were FDA approved based on a small benefit over placebo for middle aged men with known heart disease. This is called secondary prevention.
Secondary Prevention of Heart Disease in Males
Considering the media and marketing hype over statin drugs, one would think there must be something to it, so let’s take a look at the statin drug studies in the best case scenario, middle aged men with known heart disease, also known as secondary prevention. This group has proven mortality benefit, and these are the studies submitted for FDA approval for this class of drugs. Let’s take a closer look at the data from two of the most representative secondary prevention studies with statin drugs, the 4S (15-16) and the LIPID Studies (17).
4S Trial with Simvastatin in Scandinavia (15,16) – 0.6% per year
Here is a quick recap of the 4S-Trial data.
The 4S trial was done on 4444 patients who had known heart disease, randomized to simvastatin or placebo, and followed for 5.5 years. At the end of the follow up, they reported 182 deaths in the statin drug group (8.2 %) and 256 deaths in the placebo group (11.5% ). This provided an absolute mortality benefit of 3.3% over 5.5 years, or 0.6% per year. The 6-year probabilities of survival for placebo was 88.5 % and for simvastatin was 91.8%, a difference of 3.3%.(15-16)
LIPID Pravastatin Study (17) – 0.5% per year
Here is a quick recap of the LIPID Trial data.
9,000 patients with unstable angina and history of myocardial infarction were randomized to either placebo or Pravastatin and followed for 6.1 years.(17)
The statin group had 11% mortality and the placebo group had 14.1 % mortality over 6.1 years. This is a 3.1% mortality benefit over 6.1 years or 0.5% per year. After 6 years probability of survival in the placebo group is 85.9% and in the Statin drug group is 89%, a difference of 3.1 %. (17)
Absolute Mortality Benefit of 0.5% per year in Secondary Prevention
So, as you can see from the above, the absolute mortality benefit in the best case scenario, in secondary prevention trials, is only 0.5% – 0.6% per year. This benefit is underwhelming, and actually quite shocking that it is so minimal, especially since drug company marketing suggests much larger benefit.
Conclusion: The benefits of statin drugs have been over hyped, and adverse effects underplayed. A number of dissenting physicians have earned the label of “statin denialists” by casting doubts on statin drugs. These “statin denialists” have stated the benefits of statin drugs are minor, in the range of 0.5% per year reduction in absolute mortality for middle aged men with known heart disease. For all other categories, such as women, the elderly and healthy males, there is no benefit. Benefits of statin drugs, are related to the anti-inflammatory “pleiotropic effects” of statins, rather than any reduction in serum cholesterol which can be quite dramatic. Perpetuation of the statin drug myth is essential for maintaining drug industry profits. The financial stakes are high, so don’t expect change any time soon. Above left image: Vending machine for statin drugs.
Jeffrey Dach MD
7450 Griffin Road, Suite 190
Davie, Florida 33314
Articles with Related Interest:
Links and References:
1) Nissen, Steven E. “Statin Denial: An Internet-Driven Cult With Deadly ConsequencesStatin Denial: An Internet-Driven Cult With Deadly Consequences.” Annals of Internal Medicine.
2) Steve Nissen says the battle for patients’ hearts and minds is being lost by Larry Husten, CardioBrief July 24, 2017
3) Gill, Edward A. “Does statin therapy affect the progression of atherosclerosis measured by a coronary calcium score?.” Current atherosclerosis reports 12.2 (2010): 83-87.
4) Ware, William R. “The mainstream hypothesis that LDL cholesterol drives atherosclerosis may have been falsified by non-invasive imaging of coronary artery plaque burden and progression.” Medical hypotheses 73.4 (2009): 596-600. cholesterol atherosclerosis falsified coronary artery plaque Ware Medical Hypotheses 2009
5) Steven Nissen conflicts of interest disclosure: Dr. Nissen reports grants from Esperion Therapeutics, during the conduct of the study; grants from Amgen, grants from Pfizer, grants from Astra Zeneca, outside the submitted work; .
6) Nissen reported receiving research support from Amgen, Abbvie, AstraZeneca, Cerenis, Eli Lilly, Esperion Therapeutics, Novo-Nordisk, The Medicines Company, Orexigen, Pfizer, and Takeda and consulting for a number of pharmaceutical companies without financial compensation (all honoraria, consulting fees, or any other payments from any for-profit entity are paid directly to charity, so neither income nor any tax deduction is received).
7) Cleveland Clinic Dr. Shamelessly Promotes Statin Drugs Calling Side Effects ‘Imagined’ Wednesday, July 26th 2017 at 11:00 am Sayer Ji, Founder GreenMEdINFO
8) I Admit It: I’m A Member Of The Cult Posted by Tom Naughton in Bad Science, Media Misinformation, Random Musings…special note: to Tom Naughton…I hate you because your post is actually a lot funnier than mine…
9) Will Stopping Statins Kill People? The statin skirmishes of recent years have turned into bitter conflict. Dr. Nissen says stopping statins will lead to many deaths. What about side effects? Joe Graedon July 27, 2017
11) Cholesterol Lowering Drugs for the Elderly, Bad Idea by Jeffrey Dach MD
13) Ray KK, Seshasai SR, Erqou S, et al. Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65,229 participants. Arch Intern Med. 2010;170(12):1024-1031,
14) Redberg, Rita F., and Mitchell H. Katz. “Healthy men should not take statins.” JAMA 307.14 (2012): 1491-1492. Healthy men should not take statins Redberg Rita Mitchell Katz JAMA 2012
4S Study Seconday Prevention
Am J Cardiol. 1995 Sep 28;76(9):64C-68C.
Reducing the risk of coronary events: evidence from the Scandinavian Simvastatin Survival Study (4S). Kjekshus J, Pedersen TR. National Hospital, Department of Medicine, Oslo, Norway.
The Scandinavian Simvastatin Survival Study (4S) was designed to evaluate the effects of cholesterol reduction with simvastatin on mortality and morbidity in patients with coronary artery disease (CAD). A total of 4,444 patients with angina pectoris or previous myocardial infarction and serum cholesterol levels of 213-310 mg/dl (5.5-8.0 mmol/liter) while treated with a lipid-lowering diet were randomly assigned to double-blind treatment with simvastatin or placebo. Over the 5.4 years of median follow-up, simvastatin produced changes in total cholesterol, low density lipoprotein (LDL) cholesterol, and high density lipoprotein (HDL) cholesterol of -25%, -35%, and +8%, respectively, with minimal adverse effects.
A total of 256 patients (12%) in the placebo group died compared with 182 (8%) in the simvastatin group, a risk reduction of 30% (p = 0.0003) attributable to a 42% reduction in the risk of coronary death.
Noncardiovascular causes accounted for 49 and 46 deaths in the placebo and simvastatin groups, respectively. Major coronary events were experienced by 622 patients (28%) in the placebo group and 431 patients (19%) in the simvastatin group, corresponding to a risk reduction of 34% (p < 0.00001).
Circulation. 1998 Apr 21;97(15):1453-60.
Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S)
Pedersen TR, Olsson AG, Faergeman O, Kjekshus J, Wedel H, Berg K, Wilhelmsen L, Haghfelt T, Thorgeirsson G, Pyörälä K, Miettinen T, Christophersen B, Tobert JA, Musliner TA, Cook TJ. Aker Hospital, Oslo, Norway.
17) LIPID STUDY
Prevention of Cardiovascular Events and Death with Pravastatin in Patients with Coronary Heart Disease and a Broad Range of Initial Cholesterol Levels
The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group N Engl J Med 1998; 339:1349-1357November 5, 1998
Autopsy Studies Show No Correlation Between Serum Cholesterol and Severity of Plaque
18) Lande K, Sperry W, 1936. Human Atherosclerosis in Relation to the Cholesterol Content of the Blood Serum. Archives of Pathology. 22:301-312.
Abstract : The authors accepted the finding of previous workers that a correlation exists between the degree of arteriosclerosis in man and the lipoid content of the aorta. In fresh autopsy nmterial in 123 cases of violent death they compared the serum cholesterol content with the lipoid content of the aorta. No relationship was present in any age group. It is concluded that the incidence and severity of atherosclerosis in man is not directly correlated with the blood serum cholesterol content.-A. Lyall.
19) Paterson, J. C., Rosemary Armstrong, and E. C. Armstrong. “Serum lipid levels and the severity of coronary and cerebral atherosclerosis in adequately nourished men, 60 to 69 years of age.” Circulation 27.2 (1963): 229-236. Serum lipid levels and severity of coronary atherosclerosis in men Paterson JC Circulation 1963
No significant relationships, nor any trend toward such relationships,were found in 18 individual analyses concerning the coronary arteries. Furthermore, the mean serum lipid levels were consistently (but not significantly) higher in persons who did not have demonstrable sequelae of coronary sclerosis at autopsy than in persons who had sequelae. We conclude from these results that the validity
of the “lipid theory” of atherosclerosis remains unproved, as far as the coronarv arteries are concerned. QUOTE
20) Mathur, K. S., et al. “Serum cholesterol and atherosclerosis in man.” Circulation 23.6 (1961): 847-852. Serum cholesterol and atherosclerosis in man Mathur K S Circulation 1961 “No correlation could be observed between the serum cholesterol level and the amount and severity of atherosclerosis in the arteries. ”
21) Rabaeus, Mikael, Paul V. Nguyen, and Michel de Lorgeril. “Recent flaws in Evidence Based Medicine: statin effects in primary prevention and consequences of suspending the treatment.” Journal of Controversies in Biomedical Research 3.1 (2017): 1-10.
In summary, it cannot be considered as evidence based to continue to claim that statin discontinuation increases mortality or that statin therapy saves lives.
22) Okuyama, Harumi, et al. “Statins stimulate atherosclerosis and heart failure: pharmacological mechanisms.” Expert review of clinical pharmacology 8.2 (2015): 189-199. Statins stimulate atherosclerosis and heart failure Okuyama Harumi Expert review clin pharm 2015
23) Diamond, David M., and Uffe Ravnskov. “How statistical deception created the appearance that statins are safe and effective in primary and secondary prevention of cardiovascular disease.” Expert review of clinical pharmacology 8.2 (2015): 201-210. Deception created appearance statins are safe effective prevention of cardiovascular disease Diamond David Uffe Ravnskov Expert review 2015
Our opinion is that although statins are effective at reducing cholesterol levels, they have failed to substantially improve cardiovascular outcomes.
24) Ravnskov, U. “The fallacies of the lipid hypothesis.” Scandinavian cardiovascular journal: SCJ 42.4 (2008): 236. The fallacies of the lipid hypothesis Ravnskov Scandinavian cardiovascular journal 2008
25) Okuyama, Harumi, et al. “A Critical Review of the Consensus Statement from the European Atherosclerosis Society Consensus Panel 2017.” Pharmacology 101.3-4 (2018): 184-218.
In addition, here is what Dr Harumi Okuyama had to say about statin drugs: “No significant beneficial effects of statins for the reduction of CVD mortality have been reported since 2004/2005.”(55) Note: 2005 is when congress tightened reporting rules on drug trials.
Jeffrey Dach MD
7450 Griffin Road
Davie, Fl 33314
954 792 4663