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CLINICAL REVIEW: Deepak Bhatnagar, Handrean Soran, and Paul N Durrington Hypercholesterolaemia and its management BMJ 2008; 337: a993 [Full text]

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Ezetimibe-to be used with caution

Elliot F Epstein   (25 August 2008)

Re: Ezetimibe-to be used with caution

Mark Struthers   (26 August 2008)

Communication of risk and benefit

David Bossano   (2 September 2008)

Cholesterol management: doctors should remember their public health responsibilities

Raj S Bhopal   (7 September 2008)

Defense mechanism

David G Tucker   (7 September 2008)

Should medical science ignore the past?

Uffe Ravnskov   (7 September 2008)

Re: Should medical science ignore the past?

Raymond G Holder   (8 September 2008)

Keep the cholesterol up and carbohydrates down

Björn Hammarskjöld   (8 September 2008)

Statins: A Class Effect?

SAYAN SEN, Dr A Pirshahid, Dr A Bakhai   (25 September 2008)

Re: Statins: A Class Effect?

Raymond G Holder   (26 September 2008)

Ezetimibe-to be used with caution 25 August 2008
Elliot F Epstein, Consultant Physician (Stroke) Walsall Manor Hospital, WS2 9PS Send response to journal: Re: Ezetimibe-to be used with caution	Dr Bhatnager et al state a popular belief that combination treatment, with statin and etetimibe, may be used if cholesterol lowering targets are not met. We do accept that lowering cholesterol with statins reduces the risk of vascular events. However, there are still no randomised-controlled trials that support the benefit of ezetimibe in reducing vascular events. Until such trials are available, etetimibe should be prescribed with caution. Competing interests: None declared
Re: Ezetimibe-to be used with caution 26 August 2008
Mark Struthers, General Practitioner Bedfordshire, UK Send response to journal: Re: Re: Ezetimibe-to be used with caution	Dr Epstein is surely right to prescribe caution in the use of Ezetimibe - but there are other reasons to be cautious about the prescription of all the cholesterol lowering drugs. The West Midlands Centre for Adverse Drug Reactions (adr.org.uk), authors of the Adverse Drug Reaction Bulletin (ADRB) have recently issued a warning via the FDA concerning a "potentially increased risk of cancer associated with Simvastatin and Ezetimibe when used in combination (Vytorin)." http://adr.org.uk/?p=163 The FDA is apparently investigating a report from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial. The SEAS trial "tested whether lowering LDL-cholesterol with Vytorin would reduce the risk of cardiovascular events in individuals with aortic stenosis. A lower overall cardiovascular risk was not found with Vytorin. However, there was an additional observation that a larger percentage of subjects treated with Vytorin were diagnosed with and died from all types of cancer combined when compared to placebo during the 5-year study." Of course, there is no need to panic. The FDA believes some caution is required in interpretation of these preliminary results from SEAS bearing in mind that other large ongoing trials have not shown similar findings. The statins are very effective in reducing levels of cholesterol but their rather modest effect on the cardiovascular end point (death) appears largely independent of this undoubted fact. I believe there is good reason to be cautious about the collateral damage suffered in the ‘war on cholesterol’ and the effect of this damage on all cause end points. Competing interests: None declared
Communication of risk and benefit 2 September 2008
David Bossano, GP St Leonards Practice Send response to journal: Re: Communication of risk and benefit	Thank-you to the authors for this useful article. The interesting definition of an abnormal cholesterol could be developed further to... A desirable cholesterol level is based on the value at which the CVD risk is unacceptably high, provided that the risk can be reduced to a level which is worthwhile to the patient by treatments which are tolerable and acceptable. Assuming a 20% risk over 10 years of a significant cardiovascular event, and a 25% absolute risk reduction if statins are taken for 10 years (the threshold for statin prescribing for primary prevention); If 100 people at this level of risk take a statin for 10 years, 80 will not have a cardiovascular event who would not have had one anyway, 15 will have a cardiovascular event who would have had one anyway and 5 patients will not have a cardiovascular event as a result of (all 100) taking a statin for 10 years. In other words the annualised NNT is 200 to prevent one cardiovascular event. (Please check my calculations and correct me if I am wrong!) What I would like to ask the authors, because it is something I would like to tell patients, is by how much is ones life or healthy life extended by taking a statin. In other words are there survival data for patients on statins such that we can say not only; Statins reduce your risk of having a heart attack or stroke by a quarter and on average if 20 people (like you) took a statin for 10 years, 1 less person would have a heart attack or stroke, but also, if you take a statin for 10 years on average you will live x months longer or will remain fit and active (by avoiding a stroke) on average y months longer. I'd be very grateful if the authors or other readers could point me at such information. Best wishes, David Bossano Competing interests: None declared
Cholesterol management: doctors should remember their public health responsibilities 7 September 2008
Raj S Bhopal, Professor of public health University of Edinburgh Send response to journal: Re: Cholesterol management: doctors should remember their public health responsibilities	Rapid response: Cholesterol management: doctors should remember their public health responsibilities Editor, Bhatnagar et al's view that cholesterol management should be based on patients' predicted cardiovascular risk is a pragmatic, cost- effective solution to the delivery of individual doctor to-patient clinical care, particularly where drugs are to be prescribed. (1) Doctors also have public health responsibilities. From the public health perspective, every person in the country should be helped by the doctors to minimise their cholesterol, so that in future the mean value for the population will be below 4 mmol per litre, when we will largely dispense with pharmaceutical approaches. Doctors need to help to. My viewpoint has been expressed vigorously in Concepts of Epidemiology (2) and I quote: “Molecular science will deepen understanding of the interaction between the environment, lifestyle, and the gene…. The public health dividend from such knowledge will come from altering the pattern of risk factors in the whole population. Reducing serum cholesterol from the currently pathological level of 6 mmol per litre and more in some populations, to a physiologically normal value of 4 mmol per litre or even less, without mass medication, requires an understanding of how people and societies change. … in my 30 years since graduation I have seen professional perceptions on the level of total cholesterol requiring action drop from about 7 mmol/l, to about 6 mmol/l and now to 5 mmol/l. My figure of 4 mmol/l still looks radical but it will probably be standard by the next edition of this book.” Serum cholesterol is determined by a combination of biochemistry and what food is grown, processed, purchased, cooked, and eaten. Trade agreements, agricultural policy, marketing, and economic subsidy are crucial determinants of costs, availability and consumption. Other lifestyle factors such as physical activity are also of importance. Doctors, and not just public health ones, need to get involved in the greater challenge. Reference List (1) Bhatnagar D, Soran H, Durrington PN. Hypercholesterolaemia and its management. BMJ 2008; 337(aug21_1):a993. (2) Bhopal RS. Concepts of Epidemiology. 2 ed. Oxford: Oxford University Press, 2008. Competing interests: None declared
Defense mechanism 7 September 2008
David G Tucker, Holistic practioner hants SP10 Send response to journal: Re: Defense mechanism	The body produces cholesterol every day.The amount produced and type, will depend on the body's requirement to restore, grow and repair cellular structures within the body at that time, for the given conditions. We assume that we know better...and 'adjust' nature's millenia of evolutionary design with man-made chemicals, instead of correcting the detrimental dietry and life-style habits which precipitated the adverse health conditions. Aside from giving us the totally expected dangerous side effects from going against this situation, we exacerbate the problems by not correcting the underlying causes. Are we mad?....or should I not be concerned about the vast sums of money this Statin market increasingly generates by finding new supposedly suseptable groups...even children... to prescribe to? Fortunately, Pandora's Box is now open to all, thanks to the Internet and the allopathic model of wellness through drugs is feeling very exposed.. ...or maybe you have a convincing body of totally independent reliable research, indicating a distinct reduction in death rates due to Statin administration? I am just amazed that the human race managed to survive thus far witout the intervention of Big Pharma's wonderous benefits... Competing interests: None declared
Should medical science ignore the past? 7 September 2008
Uffe Ravnskov, independent researcher Magle Stora Kyrkogata 9, 22350 Lund, Sweden Send response to journal: Re: Should medical science ignore the past?	In their review about hypercholesterolaemia and its management Dr Bhatnager and his coworkers declared that they had selected references from reviews if they provided “a useful, objective, and comprehensive account including extensive recent references.”  By using this method the authors have missed much important knowledge from the past. Let me illustrate.      Hypercholesterolaemia was said to be one of the major causes of atherosclerosis. How come that no association between plasma cholesterol and degree of atherosclerosis has been found in post-mortem studies of unselected individuals?1-6 And how come that no angiographic trial has found exposure-response between degree of cholesterol lowering and outcome.7      A population was considered to be unhealthy when its average plasma cholesterol concentration exceeded 5 mmol/l. How come that almost all studies have shown that high cholesterol is not a risk factor for women?8 And how come that old people with high cholesterol live longer than old people with low?9-25 The latter is particularly curious because at least in Sweden more than 90% of all cardiovascular deaths occur in people above 65.      The optimal cholesterol concentration should be lower in patients with diabetes,. How come that numerous studies have found that high cholesterol is not a risk factor for diabetics?26-39      People with familial hypercholesterolaemia were said to be at a particular high risk. How come that in cohorts of such people, cholesterol is not associated with the incidence or prevalence of cardiovascular disease?40-47 And how come that these people’s risk of coronary heart disease is normal after age fifty, and that their average life span is similar to other people’s?48      A diet low in saturated fat was said to lower the risk of cardiovascular disease. How come that no randomised, controlled trial, where the only intervention was a lowering of cholesterol by dietary means has succeeded in lowering coronary or total mortality? How come that more than 20 cohort studies have found that patients with coronary heart disease have eaten the same amount of saturated fat as healthy controls?49,52 How come that almost all cohort studies have found that stroke patients have eaten less saturated fat than healthy controls?53-62 And how come that the concentration of the short-chain fatty acids in the tissues, the most reliable reflection of saturated fat intake,63-66 are not associated, or even inversely associated with coronary heart disease and degree of atherosclerosis?67-73      The authors cite a meta-analysis of 14 statin trials having shown that for each 1 mmol/l lowering of plasma LDL cholesterol, coronary and stroke events fell by about 21%. These figures were based on mean, not individual values. Curiously, no clinical or angiographic trial has found any association between degree of individual cholesterol lowering and outcome?7 There is a likely explanation, however.      If the benefit from the HMG-coenzyme A-inhibitors is due to their pleiotropic effects only, not to their inhibition of the cholesterol synthesis, a calculation using mean values should show exposure-response, also for degree of cholesterol lowering, whether cholesterol lowering by itself is useful or not.  But even if the lowering of cholesterol is unimportant, there should also have been exposure-response for cholesterol for individual values because both the pleiotropic effects and cholesterol lowering are caused by inhibition of the mevalonate pathway; a more complete blockage should result in stronger pleiotropic effects and a more pronounced lowering of cholesterol, and vice versa. As this has not been the case in any trial, the only explanation is that some of the participants had a heart attack, although their cholesterol was lowered very much, and/or that some had no cardiovascular symptoms although their cholesterol was lowered very little, meaning that high cholesterol is protective. There is also much clinical and epidemiological evidence for that.74      No doubt, statin treatment may be of benefit, but the effect is grossly overstated. The figure 17% for instance is the relative percentage; no more than a few percent of those who are taken statins gain benefit, and only if they are high-risk patients.75 Little, if any effect has been seen for women and healthy people with normal or high cholesterol. Add also that the benefit may easily be outweighed by the side effects, because they are both much more serious and much more frequent than reported in the statin trials, if reported at all.75      A critical revision of the cholesterol campaign seems urgent, preferably performed by scientists without links to the drug industry.  References 1.      Landé KE, Sperry WM. Human atherosclerosis in relation to the cholesterol content of the blood serum. Arch Pathol 1936;22: 301–12. 2.      Paterson JC, Dyer L, Armstrong EC. Serum cholesterol levels in human atherosclerosis. Can Med Ass J 1960;82: 6–11. 3.      Mathur KS, Patney NL, Kumar V, Sharma RD. Serum cholesterol and atherosclerosis in man. Circulation 1961;23: 847–52.. 4.      Marek Z, Jaegermann K, Ciba T. Atherosclerosis and levels of serum cholesterol in postmortem investigations. Am Heart J 1962; 63: 768–74. 5.      Schwartz CJ, Stenhouse NS, Taylor AE, White TA.. Coronary disease severity at necropsy. 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Circulation 1997;96: 1750-4. 34.  Niskanen L, Turpeinen A, Penttilä I, Uusitupa MI. Hyperglycemia and compositional lipoprotein abnormalities as predictors of cardiovascular mortality in type 2 diabetes: a 15-year follow-up from the time of diagnosis. Diabetes Care 1998;21: 1861-9. 35.  Hänninen J, Takala J, Keinänen-Kiukaanniemi S. Albuminuria and other risk factors for mortality in patients with non-insulin-dependent diabetes mellitus aged under 65 years: a population-based prospective 5-year study. Diabetes Res Clin Pract 1999;43: 121-6. 36.  Forrest KY, Becker DJ, Kuller LH, Wolfson SK, Orchard TJ. Are predictors of coronary heart disease and lower-extremity arterial disease in type 1 diabetes the same? A prospective study. Atherosclerosis 2000;148: 159-69. 37.  Ostgren CJ, Lindblad U, Melander A, Råstam L. Survival in patients with type 2 diabetes in a Swedish community: Skaraborg hypertension and diabetes project. 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Coronary artery disease in heterozygous familial hypercholesterolemia patients with the same LDL receptor gene mutation. Circulation 1995; 92: 290-5. 43.  Kroon AA and others. J Intern Med 1995;238: 451-9. 44.  Hopkins PN, Stephenson S, Wu LL, Riley WA, Xin Y, Hunt SE. Evaluation of coronary risk factors in patients with heterozygous famlial hypercholesterolema. Am J Cardiol 2001;87: 47-553. 45.  de Sauvage Nolting PR, Defesche JC, Buirma RJ, Hutten BA, Lansberg PJ, Kastelein JJ. Prevalence and significance of cardiovascular risk factors in a large cohort of patients with familial hypercholesterolaemia. J Intern Med 2003;253: 161-8. 46.  Neil HA, Seagroatt V, Betteridge DJ, Cooper MP, Durrington PN, Miller JP et al. Established and emerging coronary risk factors in patients with heterozygous familial hypercholesterolaemia. Heart 2004;90: 1431-7. 47.  Jansen AC, van Aalst-Cohen ES, Tanck MW, Cheng S, Fontecha MR, Li J, et al. Genetic determinants of cardiovascular disease risk in familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 2005;25: 1475-81. 48.  Neil HA, Hawkins MM, Durrington PN, Betteridge DJ, Capps NE, Humphries SE; Simon Broome Familial Hyperlipidaemia Register Group and Scientific Steering Committee. Non-coronary heart disease mortality and risk of fatal cancer in patients with treated heterozygous familial hypercholesterolaemia: a prospective registry study. Atherosclerosis 2005; 179: 293-7. 49.  Ravnskov U. The questionable role of saturated and polyunsaturated fatty acids in cardiovascular disease. J Clin  Epidemiol 1998;51: 443-460. 50.  Hooper L, Summerbell CD, Higgins JPT, Thompson RL, Capps NE, Smith GD et al. Dietary fat intake and prevention of cardiovascular disease: systematic review. BMJ 2001;322: 757–63. 51.  Ravnskov U. Diet–heart disease hypothesis is wishful thinking. BMJ 2002; 324: 238. 52.  Leosdottir M, Nilsson PM, Nilsson JA, Månsson H, Berglund G. Dietary fat intake and early mortality patterns--data from The Malmö Diet and Cancer Study. J Intern Med 2005;258: 153-165. 53.  Stemmermann GN, Hayashi T, Resch JA, Chung CS, Reed DM, Rhoads GG. Risk factors related to ischemic and hemorrhagic cerebrovascular disease at autopsy: the Honolulu Heart Study. Stroke 1984; 15:23-28. 54.  Takeya Y, Popper JS, Shimizu Y, Kato H, Rhoads GG, Kagan A. Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California: incidence of stroke in Japan and Hawaii. Stroke 1984;15, 15-23. 55.  McGee D, Reed D, Stemmerman G, Rhoads G, Yano K, Feinleib M. The relationship of dietary fat and cholesterol to mortality in 10 years: the Honolulu Heart Program. Int J Epidemiol 1985;14: 97-105. 56.  Gillman MW, Cupples LA, Millen BE, Ellison RC, Wolf PA. Inverse association of dietary fat with development of ischemic stroke in men. JAMA 1997;278: 2145-50. 57.  Ross RK, Yuan JM, Henderson BE, Park J, Gao YT, Yu MC. 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Eur J Clin Nutr 2005;59, 1417-22. 67.  Hudgins LC, Hellerstein MK, Seidman CE, Neese RA, Tremaroli JD, Hirsch J. Relationship between carbohydrate-induced hypertriglyceridemia and fatty acid synthesis in lean and obese subjects. J Lipid Res 2000;41: 595-604. 68.  Kirkeby K, Ingvaldsen P, Bjerkedal I. Fatty acid composition of serum lipids in men with myocardial infarction. Acta Med Scand 1972;192: 513-19. 69.  Lang PD, Degott M, Heuck CC, Opherk D, Vollmar J. Fatty acid composition of adipose tissue, blood, lipids, and glucose tolerance in patients with different degrees of angiographically documented coronary arteriosclerosis. Res Exp Med 1982;180: 161-168. 70.  Wood DA, Butler S, Riemersma RA, Thomson M, Oliver MF, Fulton M, et al. Adipose tissue and platelet fatty acids and coronary heart disease in Scottish men. Lancet 1984;2: 117-21. 71.  Pedersen JI, Ringstad J, Almendingen K, Haugen TS, Stensvold I, Thelle DS. Adipose tissue fatty acids and risk of myocardial infarction--a case-control study. Eur J Clin Nutr 2000;54: 618-25. 72.  Kark JD, Kaufmann NA, Binka F, Goldberger N, Berry EM. Adipose tissue n-6 fatty acids and acute myocardial infarction in a population consuming a diet high in polyunsaturated fatty acids. Am J Clin Nutr 2003;77, 796-802. 73.  Clifton PM, Keogh JB, Noakes M. Trans fatty acids in adipose tissue and the food supply are associated with myocardial infarction. J Nutr 2004;134: 874-9. 74.  Ravnskov U. High cholesterol may protect against infections and atherosclerosis. QJM 2003;96: 927-34. 75.  Ravnskov U, Rosch PJ, Sutter MC, Houston MC. Should we lower cholesterol as much as possible? BMJ 2006;332:1330-2.   Competing interests: None declared
Re: Should medical science ignore the past? 8 September 2008
Raymond G Holder, Retired engineer Home BH9 3NF Send response to journal: Re: Re: Should medical science ignore the past?	I was encouraged to see that you had published Uffe Ravnskov's letter and thus put some authoritative balance into the lemming like rush to lower cholesterol at any price. Repetitive papers continue to appear singing the praises of attacking the imagined disease of hypercholesterolemia, all in the same vein, and providing no recent trials, but turning over old work, in the name of meta analysis. A paper in the BMJ only a few weeks ago was still singing the praises of the HPS study, which can so evidently be seen to be flawed, especially in the way it eliminated reports of early side effects, and the conclusions were based more on fervent hope than factual figures.This same BMJ paper quoted the "Keys' Theorem" in relating the consumption of saturated fat to cholesterol levels. No theorem in any branch of real science would be given any credence at all if data was selected solely to fit the hypothesis. Medical research and guideline preparation would be much better served if they were not solely the work of blinkered one-specialism workers, and some criticism of their methods and objectives by other possible interested branches of medicine such as metabolism and mitochondrial problems could be seen to have been made and taken into account. There are now thousands of damaged statin users in so many countries, but those who continue to advocate statins appear to acknowledge only the minimal side effects recorded in trials, where the dangers mentioned in the Merck patents of 1990 were never put forward as possible outcomes. All others are said to be just anecdotal My near approach to death's door 5 years ago was just one such, alongside the 80 in MHRA's records who were not recognised in time and so were not saved. Long live Drs Ravnskov, Kendrick, McCully and Langsjoen, and thanks to the late Karl Folkers who brought real scientific methods and true biological knowledge to lighten up this very murky and worrying scourge of the population today. Competing interests: Statin damaged patient
Keep the cholesterol up and carbohydrates down 8 September 2008
Björn Hammarskjöld, M.D., Ph.D. SWE79291 Send response to journal: Re: Keep the cholesterol up and carbohydrates down	20 years ago the normal values of cholesterol was between 4.4 and 8.8 according to my lab’s reference values. Cholesterol is necessary for survival, brain function, membrane stabilizing, infection protection among other things. Why should we change the natures own millennii old research? Why is animal fat dangerous? Didn’t you drink your mother’s milk with 56 E% animal fat during the first months of your life? How can a nutrient tested for very many generations be bad for you? If animal fat would be bad for us, all mammals should have been extinct eons ago. Why does a cow have four stomachs? Because she eats cellulose and need those four stomachs to break down cellulose to glucose. The glucose is transformed via acetic acid to fat and protein. So the cow is a very good converter of carbohydrates to protein and fat. And, the cow collects all vitamins and minerals she needs to be OK. If you eat corn, the corn will exit the other way seemingly complete, you can not digest one single molecule of cellulose. But you can eat meat from the cow and you don’t need anything more but salt and water. Humans have been hunters since at least 10 000 generations. We hunters just have to eat meat, fish, egg and fat to stay healthy. Also, how did we treat a diabetic 87 years ago? Well, in Sweden we used fat pork and heavy cream stewed cabbage. The diabetic did not have any symptoms of his disease, lived as long as any nondiabetic. And we had more than a hundred years of experience. Today we order diabetics to eat 60 % of all energy to be carbohydrates, And then those poor diabetics need a lot of drugs including insulin to try to keep the blood glucose level down. Why do we need 60 E% carbohydrates when carbohydrates are nonessential? Protein and fat are essential, that’s why we need them but we don’t need to eat one single molecule of carbohydrates. The world is inverted today. We eat carbohydrates which are nonessential, we don’t eat fat which is essential, as well as protein. We’ve better start thinking instead of doing what others tell us to do. Competing interests: Senior citizen and can tell the truth without being hit economically
Statins: A Class Effect? 25 September 2008
SAYAN SEN, SpR CARDIOLOGY BARNET HOSPITAL, EN5 3DJ, Dr A Pirshahid, Dr A Bakhai Send response to journal: Re: Statins: A Class Effect?	Dear Sir, Dr Bhatnagar and colleagues (1) have written a useful review for non- specialists, covering a large area of work. Whilst we accept the difficulty of providing an entirely comprehensive account of such a fast moving field, we would like to comment on the treatment sections of the article. The benefits of statins are regarded as a class effect; however, there are differences between statins in addition to their varying effect on lipid profile. Statins vary in their metabolism and this affects their potential for drug interaction. Simvastatin and atorvastatin are metabolised via the CYP3A4 pathway. Concurrent therapy with drugs that interfere with CYP3A4 pathway (such as anti retrovirals, cyclosporine, digoxin, diltiazem and anti fungals) may lead to statin accumulation and an increased propensity for myopathic side effects. Statins not metabolised via this pathway such as pravastatin, rosuvastatin and fluvastatin should be considered in these patients. Furthermore, whilst the incidence of myositis is now less than 0.5%, it does appear to be less frequent with hydrophilic statins such as pravastatin (2,3). This is thought to be secondary to less muscle penetration (4) making hydrophilic statins a suitable therapeutic option for patients hindered by myopathic complaints on lipophilic statins such as simvastatin/ atorvastatin. With regard to adjunctive therapy such as ezetimibe, despite an additional absolute 15% reduction in LDL cholesterol, the combination of simvastatin and ezetimibe has shown neutral results in recent trials (5, 6) thus far. We await the results of the IMPROVE-IT trial (7), in the interim NICE suggests it is reasonable to employ the combination to achieve LDL target. The increase in cancer incidence in the recent SEAS trial is surprising. However, it would not be the first lipid-altering drug with unexpected adverse effects. The increase in mortality and blood pressure with Torcetrapib in phase III studies has lead to Pfizer halting trials and their development programme for Torcetrapib. In contrast, the safety profile for statins is known. Ten year follow up from 4S and WOSCOPS trials have not shown an increased incidence of cancer with statins (8,9). Thus, until we have the results of IMPROVE -IT, perhaps alternative statins such as atorvastatin or rosuvastatin, which have more prognostic and safety data should be employed if target is not achieved with simvastatin. Guidelines aim to simplify decision-making, suggesting simvastatin for all with dose adjustment and adding ezetimibe if necessary. However, this may not always be optimal for individual patients. The practicing physician must therefore also be aware of statin subtypes, interactions and the benefits and pitfalls of new adjunctive therapies. Dr Sayan Sen MRCP SpR Cardiology, Barnet & Chase Farm Hospitals NHS Trust Dr A Pirshahid. Clinical Fellow, Barnet & Chase Farm Hospitals NHS Trust Dr A Bakhai FRCP Consultant Cardiologist, Barnet & Chase Farm Hospitals NHS Trust 1.Hypercholesterolaemia and its management. Deepak Bhatnagar, Handrean Soran, and Paul N Durrington BMJ 2008;337:a993, doi: 10.1136/bmj.a993 2..Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. Graham DJ; Staffa JA; Shatin D; Andrade SE; Schech SD; La Grenade L; Gurwitz JH; Chan KA; Goodman MJ; Platt R JAMA 2004 Dec 1;292(21):2585-90. Epub 2004 Nov 22 3.Safety and tolerability of pravastatin in long-term clinical trials: prospective Pravastatin Pooling (PPP) Project. Pfeffer MA; Keech A; Sacks FM; Cobbe SM; Tonkin A; Byington RP; Davis BR; Friedman CP; Braunwald E. Circulation 2002 May 21;105(20):2341-6 4.Differential sensitivity of C2-C12 striated muscle cells to lovastatin and pravastatin. Gadbut AP; Caruso AP; Galper JB J Mol Cell Cardiol 1995 Oct;27(10):2397-402 5. Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia. J Kastelein MD, F Akdim MD, E Stroes MD, et al New Engl J Med 2008 358:1431-1443 6. Design and Baseline Characteristics of the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) Study. Rossebo AB; Pedersen TR; Allen C; Boman K; Chambers J; Egstrup K; Gerdts E; Gohlke-Barwolf C; Holme I; Kesaniemi VA; Malbecq W; Nienaber C; Ray S; Skjaerpe T; Wachtell K; Willenheimer R Am J Cardiol. 2007 Apr 1;99(7):970-973. Epub 2007 Feb 15 7. IMPROVE-IT: Examining Outcomes in Subjects With Acute Coronary Syndrome:Vytorin (Ezetimibe/Simvastatin) vs Simvastatin. In progress. Clinicaltrials.gov 8.Mortality and incidence of cancer during 10-year follow-up of the Scandinavian Simvastatin Survival Study (4S). Strandberg TE; Pyorala K; Cook TJ; Wilhelmsen L; Faergeman O; Thorgeirsson G; Pedersen TR; Kjekshus J. Lancet 2004 Aug 28;364(9436):771-7. 9. Long-term follow-up of the West of Scotland Coronary Prevention Study. Ford I; Murray H; Packard CJ; Shepherd J; Macfarlane PW; Cobbe SM. N Engl J Med. 2007 Oct 11;357(15):1477-86. Competing interests: None declared
Re: Statins: A Class Effect? 26 September 2008
Raymond G Holder, Retired engineer Home BH9 3NF Send response to journal: Re: Re: Statins: A Class Effect?	It is amazing that Sayan Sen et al should quote a figure of less than 0.5% for the incidence of myositis from statin use, when many have reported that it is nearer 20% in the general situation. The low figure appears to arise from trial reports, which fail to count these events fully. The larger figure is also borne out by affected patient reports on websites where they seek help for the problem, not available from their doctors, and from personal stories of folk known to me. I am also surprised that the letter says that the depth of penetration of the statin into the muscle has a bearing on the severity of myositis. Merck explained in its 1990 patent applications that reduction of Q10 production in the mevalonate pathway, in which all statins work, is the cause, but this fact has not been allowed to trickle down to coal face clinicians. Another facet on lowered lipids was put forward this month in the American Heart Journal by P Tamara et al where 17,000 patients hospitalised with heart failure, had their lipid profile taken, and their progress was analysed, covering 2 years. 46% were on statins. Each 10ml INCREASE in cholesterol level was associated with a 4% DECREASED risk of in-hospital mortality from heart failure. Food for thought there, especially by the Heart Czar, who says that the older generation should have a chance to "share the benefits of statin therapy" (perhaps a place further up in the queue at the undertakers??) Competing interests: Statin damaged patient