19 Sept 2014 update: ABSTRACT: readers of this column recently commend its statin commentary, last updated in June, about the controversy of statins in primary prevention of cardiovascular disease CVD. This update now reviews crucial major recent evidence that the marketing hype of “statin deficiency” in the average aging population is a dangerous fabrication (eg Vytorin) of the $billion Disease and Drug corporate industry – especially when statins inhibit omega3 and CoQ10 which like other human micronutrient protectors- magnesium, iodine, arginine, carnitine, ribose, vitamins , B, D3, C & K2, and human sex hormones – are increasingly deficient or imbalanced in an aging western population and urban convenience food diet.
Margaret McCartney general practitioner, Glasgow writes : We lack the tools to help patients decide about statins BMJ 2014; 349 doi: The National Institute for Health and Care Excellence (NICE) recently approved atorvastatin for people in England and Wales who have a 10% risk of a cardiovascular event within 10 years; it had previously been a 20% risk.1 GPs are advised to treat such people—which includes everyone older than 85—and to continually review everyone else in case they pass the 10% threshold.
This decision on funding statins is based primarily on cost effectiveness to the NHS.2 The press release from NICE mentioned the potential benefit to the population (namely, it “could help prevent up to 28 000 heart attacks and 16 000 strokes each year”3) but not the absolute benefit to the individual.
But life is more complicated than that: people make choices for multiple reasons. Many patients stop taking statins after starting them4; others, faced with the choice of taking a drug with a small chance of benefit, would rather not do so; and some people will want to take them no matter how low their risk may already be.
We lack the tools to accurately predict individual risk at such low thresholds—leading to overtreatment and, to a lesser extent, non-identification of risk.5 The general practice cake is finite; cutting a bigger slice for healthy people at lower risk means a smaller slice for people who have symptoms and are unwell. The chance of a longer life is offered to people who are willing to take tablets consistently, but we know that these compliant patients are already more likely to live longer, even when taking a placebo.6 7 This policy, which benefits people who are already the healthiest, has the potential to widen health inequalities.
Who is keeping an overview of where NICE is taking us? The conflicts of interest among the members on its drafting panels are buried in minutes rather than in the guidance itself, and we still lack public access to most of the trial data that NICE uses.8 But we are told to press ahead regardless when, most bewildering of all, we don’t have a decent shared decision aid—designed and tested for the five million more people advised to take statins—about the benefits and harms of statinisation and the management of cardiovascular risk.
“Should I take statins?” is a question asked of GPs every day. We urgently need better tools to allow guidance to guide, rather than dictate new targets. Our lack of resources to deal with such a common question simply isn’t acceptable.
A 2013 Italian Statin HMGA study Pasin ea shows that statins- cholesterol-busters- do not help patients with sepsis.
A 2010 review Yue ea of all published studies in 3,022 postmenopausal women (mean age, >62.7 y), showed that statin use doesnt prevent fractures or increases bone density.
why should synthetic designer metabolic poisons – statins- be expected to help peripheral conditions like fracture risk and menopause? when statins promote diabetes – insulin resistance, and block healthy metabolism throughout the body, in brains, muscles, kidneys, skin- but especially lowering liver manufacture of cholesterol that is one of our top lifegivers for our needed reproductive and adrenal steroids- including our two prime anabolic steroids( vitamin D3 and androgen). And statins increase the risk of highly malignant Merkel Cell skin carcinoma by 25%, as well as dermatitis eg Ma . ..
We have known for ~forty years that while anticholesterol drugs are valuable for rare people with severe hypercholesterolemia HCH risk of vascular disease, statins’ longterm adverse effects are numerous, and there has never been evidence to justify their routine mass use for mild to moderate HCH- ie CVS risk below ~15 to 20% in 10 years- despite the Cholesterol-statin industry investing multimillions in their promotional trials and in their lobbyists.
Wiki says ” In FH, Initial studies showed increased activity of HMGA but more showed that this did not explain the very abnormal cholesterol levels in FH patients. The binding of LDL to its receptor, and effects of impaired binding on metabolism proved to be the underlying mechanism for FH. Heterozygous FH is a common genetic disorder inherited in 1:500 people in many “European” populations – the Afrikaner, French Canadians, Lebanese Christians, and Finns have high rates of specific mutations that make FH particularly common in these groups. Homozygous FH is much rarer, occurring in 1 in a million births. Heterozygous FH is normally treated with lipid lowering agents – statins, bile acid sequestrants.. . Homozygous FH often does not respond to medical therapy and may requires radical other treatments.
But ezetimibe as an addon to statin eg in Vytorin has been thoroughly discredited. As Forbes.com said last year, Pharma & Healthcare 2013 The Fate Of New Cholesterol Drugs Depends On IMPROVE-IT “.But Improve-It was not completed as planned in 2013. The new American guidelines delivered a strong statement questioning the increasingly controversial theory that LDL lowering by itself is beneficial. “We found that non-statin therapies really didn’t provide an acceptable risk reduction benefit compared to their potential for adverse effects in the routine prevention of heart attack and stroke,” IMPROVE-IT is the large, seemingly endless outcomes trial studying Vytorin, which has been a blockbuster drug for Merck. But the drug’s reputation, and its sales, have diminished in recent years because of a raging controversy over the lack of any evidence for clinical benefit. Vytorin lowers LDL cholesterol but no one knows if it improves outcomes. The IMPROVE-IT trial is supposed to resolve this controversy next year, but it will do so only as the patent on the drug nears expiration. There’s a really good analogy to help understand the way IMPROVE-IT could impact the fate of the PCSK9 inhibitors. Just recently supporters of Amarin’s fish oil pill Vascepa thought the drug would coast to approval for a broad new indication. Their optimism was based largely on an agreement with the FDA that did not require a large outcome study before approval. But over the past few years several large outcome trials– not entirely dissimilar to IMPROVE-IT– failed to demonstrate clinical benefit for drugs that, like Vascepa, lowered triglycerides. The FDA tore up its earlier agreement with Amarin. In all likelihood Vascepa will not gain the new indication it seeks until an ongoing outcome study is successfully completed. The other Merck CVS drug trial of Tredaptive, a combination of simvastatin and niacin B3 vitamin, failed to show the new drug was better than a statin alone.
However, the Improve-It trial already failed when it showed no significant target benefits of more intensive LDLC lowering by it’s planned 2.5 years finish ie 2010 ; so numbers (10 000 to 18000) and time were increased to 18000 subjects, to finish now.. The latest is that results will be released 17 November…
what do other STATIN trials show? A Canticle for Statins?
COMPARISON OF THE 2011 CAMBRIDGE METANALYSIS AND 2013 COCHRANE STATIN METANALYSES:
BUT their full published paper tables showed that statin use – in a mean time of only 3 years- ” increased Diabetes 18% from 2.4% on placebo to 2.9% on statin; with more fatal strokes, liver, renal, arthritis adversity. and all-cause mortality from 5-1 to 4.4%; NUMBER NEEDED TO TREAT NNT 96. THE ABSTRACT DOES NOT GIVE THESE GLUM NUMBERS, that statins benefit only 1 in a hundred. BUT the dull paper states “Only the JUPITER trial showed strong evidence of a reduction in total mortality.“
so while the Cochrane study patients were 5 years younger but had baseline LDLC 19% higher, than in the Cambridge analysis, ie by age and LDLC, the Cochrane analysis could still not show meaningful reduction in mortality other than in the disputed Jupiter study.. But the Cochrane trials had only 1/8th of the diabetics in the Cambridge analysis.
So what the innocuous abstract of the London UK Cochrane review failed to say is that, in their full paper (available on application) weighted by the biased Jupiter trial, to lower mortality by 14% in about 3.5years, to avoid one death, 96 well people need to take fairly vigorous dose statin for 1 to 5.4 years – or 1 patient for a few hundred years– with serious risks of diabetes (up 18%), liver, kidney, myopathies, peripheral neuropathy, intracerebral hemorrhage (ICH), and other diseases of the central nervous system (eg cognitive impairment, depression, sleep disorders, nightmare, and headache- . mood (suicide risk increased 2.5 fold – Davison & Kaplan 2014 Canada );
and (unlike the anticancer benefits of metformin and vitamin D3) no benefits in reducing cancers rates. Such bad risk: benefit ratio confirms what has always been known, that there is no place for mass long-term consumption of statin whether in a mythical Polypill (Wald and Law 2003– with adverse Bblocker, ACEI and aspirin,) or even more farfetched added to our diet staples- water, bread etc..
It is common cause that diabetes increases major risks 4 fold; so advocating 96 well people to take a statin to lower mortality by 1 case in 3.5 years ie 330 patient-years while >3% develop diabetes, stroke, depression, myositis, hepatorenal and other major complications, is negligence, when patients do so much better on metformin plus other natural proven life-extending supplements like fish oil, coconut oil, vitamins esp vit D3 & K2, minerals etc.
This is in contrast to metformin prevention in similar overweight well people, which lowers all risks by at least a third, with no adverse effects provided dose is started low and titrated to tolerance ie ~250 to 2500mg a day. THE BMJ STATIN FUROR JUNE 2014:
Just last month, the long-awaited independent review of the BMJ June 2014 STATIN publication (of articles denouncing the value of statins for mass primary prevention ) confirmed that the BMJ editors under Dr Fiona Godlee were correct in standing by the June papers that there is no mortality benefit from statin treatment in people at less than a 20% 10-year risk of cardiovascular disease, as Canada implements., The panel, chaired by Dr Heath with six internationally renowned experts, concluded the journal had handled the two articles appropriately and that its processes were timely and reasonable.
one from India describing many promising new competitors to displace statins; one from Oxford University warning yet again of the adverse effects of anticholesterols, this time by CETP inhibitors; and one from New York University mocking the wannabe Statinopause, statin deficiency:
George, Elangovan ea in India J Cardiovasc Pharmacol Ther. 2014 Jul Look into the Crystal Ball -Upcoming Drugs for Dyslipidemia:. say: . Although statins are effective anti-dyslipidemic drugs, their use is fraught with issues such as failure of adequate lipid control in 30% of cases and intolerance in select patients. The limited potential of alternatives such as fibrates, bile acid sequestrants and niacin has spurred search for novel drug molecules with better efficacy and safety, eg promising cholesteryl ester transfer protein CETP inhibitors such as evacetrapib and anacetrapib; (MTP) inhibitors eg lomitapide; Apo CIII inhibitors eg mipomersen; PCSK9 inhibitors eg evolocumab, alirocumab; farnesoid X receptor modulation; and Lp-PLA2 inhibition. While it may not be an easy proposition to dismantle statins from their current position as a cholesterol reducing agent and as a drug to reduce coronary and cerebro-vascular atherosclerosis, our improved understanding of the disease and appropriate harnessing of resources using sound and robust technology could make rapid in-roads in our pursuit of the ideal anti-dyslipidemic drug.
Miller NE. University of Oxford, UK in F1000Res.2014 Jun warns Time to think again about . CETP inhibitors and cardiovascular disease: Inhibition of cholesteryl ester transfer protein (CETP) lowers plasma LDLC concentration and raises HDLC, suggesting it might prevent CVD. From the outset, however, the concept has been controversial owing to uncertainty about its effects on HDL function and reverse cholesterol transport (RCT). Although there has long been good evidence in rabbits that CETP inhibition reduces atherosclerosis , the first information on CETP as a CVD risk factor in a prospectively followed cohort was not published until after the first Phase 3 trial of a CETP inhibitor had begun. The worrying finding that in humans CVD incidence was related inversely to plasma CETP has since been reproduced in each of five further prospective cohort studies. Similar results were obtained in subjects on or off statin therapy, for first and second CVD events, and for mortality as well as CVD morbidity. Additionally, two recent studies have found alleles of the CETP gene to be associated with an increased risk of myocardial infarction. Meanwhile, CETP gene transfer in mice was found to increase RCT from peripheral macrophages in vivo, and human plasma with high CETP activity was shown to have a greater capacity to remove cholesterol from cultured cells than plasma with low activity. This mounting evidence in humans and mice for a protective function of CETP has been given remarkably little attention, and indeed was not mentioned in several recent reviews. It appears to show that CETP inhibition does not test the HDL hypothesis as originally hoped, and raises a pressing ethical issue regarding two Phase 3 trials of inhibitors, involving more than forty thousand subjects, which are currently in progress. As the weight of evidence now clearly supports an adverse effect of CETP inhibition on CVD, an urgent review is needed to determine if these trials should be discontinued.
Coenzyme q10 therapy 2014 .Garrido-Maraver J1, Sánchez-Alcázar ea . at Seville Universities say coenzyme Q10 (CoQ10) have key role in mitochondrial bioenergetics; antioxidant; obligatory cofactor for uncoupling proteins and a modulator of the mitochondrial transition pore; expression of genes ; human cell signaling, metabolism and transport. CoQ10 deficiencies are due to autosomal recessive mutations, mitochondrial diseases, aging-related oxidative stress and carcinogenesis processes, and statin treatment. Many neurodegenerative disorders, diabetes, cancer, and muscular and cardiovascular diseases have been associated with low CoQ10 levels as well as different ataxias and encephalomyopathies. CoQ10 causes no serious adverse effects in humans. Oral a CoQ10 is a frequent antioxidant used in many diseases that may provide a significant symptomatic benefit.
Michel de Lorgeril ea .Universite Joseph Fourier, Grenoble France BMC Med.2013 ask: do statins inhibit omega-3?. Recent findings on the health effects of omega-3 fatty acids and statins, and their interactions. .Early randomized controlled trials (RCTs) demonstrated the health benefits of omega-3 fatty acids (n-3), whereas recent RCTs were negative. We now address the issue, focusing on the temporal changes having occurred: most patients in recent RCTs are no longer n-3 deficient and the vast majority are now treated with statins. Recent RCTs testing n-3 against arrhythmias suggest that n-3 reduce the risk only in patients not taking a statin. Other recent RCTs in secondary prevention were negative although, in a post-hoc analysis separating statin users and non-users, non-significant protection of n-3 was observed among statin non-users whereas statin users had no effect. Recent RCTs testing statins – after the implementation of the New Clinical Trial Regulation in 2007 – are negative (or flawed) suggesting that the lack of effect of n-3 cannot be attributed to a parallel protection by statins. Finally, statins favor the metabolism of omega-6 fatty acids (n-6), which in turn inhibits n-3; and contrary to n-3, they increase insulin resistance and the risk of diabetes. Thus, n-3 and statins are counteractive at several levels and statins inhibit n-3.
ie statins undo the proven benefits of omega3 and CoQ10. .
VITAMIN D AND CHD:
Charles Glueck ea at the same Cincinnati Jewish Hospital. in Med Hypotheses. 2011 describe HOW Vit D repletion reverses statin intolerance in 91% of statin-intolerant patients. Symptomatic myositis-myalgia in hypercholesterolemic statin-treated patients with concurrent vitamin D deficiency leading to statin intolerance may reflect a reversible interaction between vitamin D deficiency and statins on skeletal muscle. Myositis-myalgia is the most common cause of statin intolerance, leading to cessation of statin use, with consequent failure to lower LDL cholesterol to target levels for primary and secondary prevention of cardiovascular disease (CVD). Despite published and new empirical evidence, the medical establishment has refused to accept it, requiring placebo-controlled, double-blind studies, none having been reported to date.
Specific Critiques of the Jupiter study and Contrasting results from other studies: :
Conclusion: these references reviewed confirm that is no justification for the myth of routine use of statins for primary prevention in the average population, especially in view of their risks, especially increase in diabetes, and the availability of safe and far more globally healthgiving natural antiaging antioxidant energizing insulin-sensitizing supplements that do a far better job of reversing both CVD and all other major diseases. .
update 16 June 2014 as this column has argued since 2008 (and this author for 40 years in refusing to take them for lack of proof)- given their numerous serious and nuisance harms- there never has been good enough evidence to justify synthetic designer cholesterol-busters for primary prevention with mild-to-moderate cholesterolemia ie without the presence of cardiovascular disease;
in contrast to harmless multipurpose (antiatheroma antidiabetic antithrombotic antihypertensive anticancer all-disease prevention) micronutrient supplements like fish oil, coconut oil, DMSO, metformin, vitamins esp C D & K2, minerals esp magnesium, chromium, zinc, iodine; , human nonoral HRT, CoQ10, arginine, carnitine, carnosine ; numerous mixed medicinal herbs; etc.
In the Statin-use debate creates furor at BMJ CMAJ on June 16, 2014, Carolyn Brown argues “Statins are beneficial for people with proven coronary artery disease, but a recent BMJ article questioned their use as a prophylactic measure. “Are statins going to have a big impact on coronary artery disease or are they going to be one of the big mistakes that the medical profession has made?” That’s the question asked by Dr. James Wright, a Canadian who co-authored an analysis of the evidence on statins that appeared in the British Medical Journal (BMJ) in October 2013.
” It seems like a straightforward question, but that article has led to a furor in the United Kingdom, with a well-known researcher calling for its retraction and the BMJ editor-in-chief Fiona Godlee defending the journal’s publishing process on radio and television. At issue is the clinical uncertainty about the preventive use of statins. “We’re fairly certain that benefits outweigh the harms in people with proven coronary artery disease (CAD). That’s based on a highly statistically significant but modest reduction in total mortality,” says Wright, who is managing director and chair of the Therapeutics Initiative (TI) at the University of British Columbia. But he says most prescriptions for statins are aimed at preventing CAD.
“The evidence for this is not as rigorous and serious adverse effects have been documented. The UK’s National Institute for Health and Care Excellence (NICE) recently proposed extending preventive use of statins from patients who have a 20% chance of developing CAD in the next 10 years (its current guideline) to those with a 10% risk. This has led to a debate over the accuracy of risk calculators, unnecessary prescribing in seniors (since age is a major risk factor) and adverse effects. Canada’s guidelines recommend statin therapy in patients with risk below 20% only if their levels of cholesterol or other indicators exceed certain thresholds. Wright believes the statin issue has become heated because “so many people are taking them. They have been in the news so much and there [is] so much money being spent on them.” “Publication of our article has reignited the debate,” says Dr. Kamran Abbasi, international editor of the BMJ, who spoke on behalf of Godlee. “There are people who disagree vehemently on this issue. They can’t reach any sort of consensus on it at the moment.” The BMJ article re-analyzed data from the Cholesterol Treatment Trialists (CTT) Collaboration meta-analysis and cited adverse effects rates from various studies.
” Sir Rory Collins, a researcher at Oxford University and head of the CTT group, corresponded directly and met with Godlee in December 2013 about the article, calling for a retraction. He has also stated his view in media interviews. As a result of Collins’ complaint, the article was corrected, as the authors agreed that they had erred in reporting rates of side effects from the observational study. Wright says, “The issue around side effects is just that there is some harm.” The analysis had cited a rate of statin-related adverse effects of 18%; in fact, the original study found 17.4% of patients had a “statin-related event” but only approximately 9% discontinued statin therapy as a result. The correction affirmed that the CTT study failed to show that statins reduced the overall mortality risk in patients with a less than 20% risk of CAD over 10 years. Godlee also published an editorial explaining the journal’s decisions on how to handle the controversy and appointed an independent panel to rule on whether a retraction is warranted. Collins says he has submitted detailed material to this panel and maintains that there remain “extensive problems” with the analysis paper, beyond what the correction addressed. Charlotte Haug, vice-chair of the Committee on Publication Ethics (COPE).
update 2010 A new review, this time from a top team in France, further demolishes the deceptive Jupiter trial promoting rosuvastatin Crestor, confirming that it was fatally flawed:
Cholesterol lowering, cardiovascular diseases, and the rosuvastatin-JUPITER Crestor controversy: a critical reappraisal.
Michael de Lorgeril ea conclude: ” The results of the trial do not support the use of statin treatment for primary prevention of cardiovascular diseases and raise troubling questions concerning the role of commercial sponsors.”
This concurs with the fraud of modern medicine increasingly pursued by combined Drug Industry and Government Regulator conspiracy, including www.lef.org/…/Media-Attempts-to-Misrepresent-Scientific-Findings.htm
and Univ California San Diego alone reports 300 cases of statin-related myopathy.
contrast this with the trial report last week from a hypertension unit in Israel where a simple combination of vits C & E, coQ10 and selenium for 6 months – with no risks- lowered arterial stiffening, hypertension, lipidemia and glucose.
so why use statins except in severe familial lipidemia?
Feb 4th 2010
Early last year this column pointed out that the JUPITER trial was another nail in the coffin of primary use of statins.
Now a University California Davis team concur further in “Another look at the results of the JUPITER trial… that many of the participants did not receive care consistent with current standards. Thus, the benefit of statin therapy would have been more difficult to demonstrate if standard therapeutic recommendations had been followed. In conclusion, these considerations cast doubt on the contention that statin therapy should be initiated in apparently healthy individuals on the basisof elevated high-sensitivity C-reactive protein levels.“