Should Women Take Cholesterol Lowering Drugs To Prevent Heart Disease?
Main Category: Heart DiseaseAlso Included In: Statins; Cholesterol; Women's Health / Gynecology
Article Date: 11 May 2007 - 1:00 PST
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Women in western countries are more likely to die from heart disease than from cancer. In this week's BMJ, two experts debate whether women should be offered cholesterol lowering drugs as a preventive treatment.
For women who are at moderately high risk of heart disease, use of drugs should not be ruled out, argues Professor Scott Grundy from the University of Texas.
There is general agreement that both men and women with established cardiovascular disease are at high risk and should get intensive cholesterol lowering therapy.
The essential question here is whether women as well as men should be considered for drug therapy when they do not have established cardiovascular disease, but who are deemed to be at moderately high risk, according to the guidelines.
Trials involving both men and women at moderately high risk have shown overall risk reduction from cholesterol lowering therapy, but not enough women were included to provide a definitive result, he explains.
Until a large-scale clinical trial is carried out to test the efficacy of cholesterol lowering in women at moderately high risk, drug therapy should be avoided in most lower risk women, he says. But in those who have multiple cardiovascular risk factors and who are projected to be at moderately high risk, use of drugs should not be ruled out.
But GP Malcolm Kendrick disagrees. Not only do statins fail to provide any overall health benefit in women, they represent a massive financial drain on health services, he says.
He believes the evidence of benefit is not strong enough. He points out that, to date, none of the large prevention trials has shown a reduction in overall mortality in women, and one suggested that overall mortality may actually be increased. This, he says, raises the important question whether women should be prescribed statins at all.
Statins also represent the single greatest drug expenditure in the National Health Service, he says. In 2006, the cost in England was £625m and is expected to reach £1bn in 2007. This money could be diverted to treatments of proved value.
Some studies also suggest that statins carry a substantial burden of side effects, he adds.
He concludes that spending hundreds of millions on a treatment that has no proved benefit and may cause serious harm goes against the rationale of evidence based prescribing.
"Head to Head: Should women be offered cholesterol lowering drugs to prevent cardiovascular disease?"
BMJ Volume 334 pp 982-3
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Why Statins Should Not Be Prescribed For Women
posted by Paul J. Rosch M.D. on 12 May 2007 at 8:00 amIn addtion to the objections raised by Kendrick that were supplemented in a rapid response by Ranvskov to Grundy's argument in the current British Medical Journal issue
(BMJ Volume 334 pp 982-3) the following issues should be emphasized.
Grundy's conclusions are based on Framingham data describing cholesterol as a "risk factor" for coronary heart disease, which implies that it is a causative agency. However, like hundreds of others so-called "risk factors", elevated cholesterol is actually a "risk marker", that merely shows some statistical association with various coronary events. A deep earlobe crease and premature baldness are also in this category but correcting them with plastic surgery or a hair transplant does not prevent coronary disease and neither does lowering cholesterol. In point of fact, follow-up Framingham data revealed a direct association between falling cholesterol levels over the first 14 years of the study and increased mortality rates over the following 18 years. For men above the age of 47, those with low cholesterol had mortality rates greater than those with high cholesterol. Those whose cholesterol had decreased spontaneously over 30 years were at greater risk of dying from heart disease than those whose cholesterol had increased. "For each 1% mg. drop in cholesterol there was an 11% increase in coronary and total mortality." In addition, the majority of patients with heart attacks do not have elevated cholesterols.
The MRFIT (Multiple Risk Factor Intervention Trial), which was the largest and most serious effort to prove the links between the original Framingham heart disease risk factors of cholesterol, cigarette smoking and hypertension, showed no significant difference in coronary disease between the intervention group where these presumed etiologic factors were reduced and controls. After ten years of adhering to a diet in which cholesterol consumption was cut by 42 percent, saturated fat consumption by 28 percent and total calories by 21 percent, there was a slight lowering of coronary heart disease mortality rates. However, this benefit was far outweighed by significantly increased total death rates from hemorrhagic stroke, cancer, suicide, accidents and violence.
Kendrick correctly raises the issue of costs, which is a far greater problem in the U.S., due to the hundreds of millions of dollars spent on direct to consumer TV and other media advertising. This may be a factor in the exorbitant costs of statins, which are over 4,000 percent for Zocor (simvastatin) and over 4,700 percent for Lipitor (atorvastin) more than the cost of raw materials. With the possible exception of New Zealand, where it may soon be banned, the United States is the only country that permits direct to consumer advertising, which encourages the use of drugs for individuals in whom no benefits have been shown. As a result, there are currently several suits against Pfizer for false advertising to women and anyone over 65. As Grundy indicates, the Framingham data show that "only a few women without cardiovascular disease have a 10 year risk of coronary heart disease over 10% and the vast majority of these are over 60. He also argues that estimating absolute risk before starting statin therapy will insure that statins will not be prescribed inappropriately. However, the claim that "For every 1% fall in cholesterol there will be a 2% reduction in risk for coronary heart disease" refers to relative risk, which is deceptive and quite different. A study may show that after five years on a statin, patients had 34% fewer heart attacks than controls on statins, so that there is 34% relative risk reduction. What you are not told is that the absolute risk reduction is only 1.4% and that if the drug is taken by seventy-one people every day for five years, it will prevent one person from having a heart attack - but it is not known if that person will be you. Indeed, you will never see an advertisement stating that a statin reduces heart attacks, if you look at the fine print on the bottom in mice type, which is mandated in some instances, it will say: Lipitor has NOT been shown to prevent heart disease or heart attacks.”
”Crestor has NOT been shown to prevent heart disease or heart attacks"
Finally, any alleged cardioprotective effects of statins are clearly not related to lowering cholesterol or LDL since they are seen when these values are normal or low and a clear dose response relationship has never been demonstrated. Benefits are more likely due to anti-inflammatory, antithrombotic or other "pleiotropic" effects that do not correlate with lipid levels. Therefore, current criteria for dosage and duration of statin therapy based on achieving an arbitrary LDL level that few can achieve will only guarantee higher statin doses for longer periods of time that are known to increase the incidence of adverse side effects. This may account for the well-known poor adherence to statin therapy.
Physicians and the public have a right to know about views contrary to the current cholesterol-coronary disease hypothesis but it is difficult to disseminate this information because of the powerful cholesterol cartel of manufacturers of cholesterol lowering products, low fat foods and blood testing equipment. Medical publications and the media do not want to risk losing their lucrative advertising revenues and those who oppose this dogma suffer severe retaliation and ad hominem attacks. Kilmer McCully lost his laboratory support and could not find employment for two years for suggesting that homocysteine might be as important a cause of coronary disease as cholesterol. Uffe Ravnskov's book, The Cholesterol Myths was burned on a Finnish TV program and he was unjustly defamed on a Dutch TV program that aired his views. The British Medical Journal should be highly commended for sponsoring this open debate based on scientific data.
Prior to the posting of this debate, where both sides had the opportunity to explain their views and cite relevant supportive references, the vast majority of physicians saw no objection to prescribing statins for women. The last time I looked at the results of a poll of those who had the opportunity to consider the pros and cons, over 95% now voted no. Decide for yourself.
Framingham Study Status
posted by Jeff Cable on 13 May 2007 at 4:11 amThe Framingham study referred to by Paul Rosch MD, was a study that began in Framingham, Massachusetts, USA, in 1948. The reader would naturally assume that Framingham was a well considered study, that had helped to advance medical knowledge and made a significant contribution to knowledge of heart disease. The study initially included 5,209 men and women who all were between the ages of 30 and 62.
The chronological list of findings first mentions cholesterol in 1961, with the words... "Cholesterol level, blood pressure, and electrocardiogram abnormalities found to increase the risk of heart disease". The final piece of the 1961 statement of research milestones had implicated 'cholesterol level' in this triad of factors that supposedly had implications for increasing the risk of suffering with heart disease. In 1970, the director of the Framingham Heart Study made the following statements to The News; a newspaper for Framingham and Natick.
Page 36 The News, Framingham-Natick, Friday October 30th 1970
Findings of the Framingham Diet Study Clarified
Framingham - Although there is no discernible relationship between reported diet intake and serum cholesterol levels in the Framingham Diet study group, "it is incorrect to interpret this finding to mean that diet has no connection with blood cholesterol" Dr William B Kannel, director of the Framingham heart study has stated.
"It has been repeatedly demonstrated that blood cholesterol levels can be altered by changes in diet; and dietary alteration is still the most acceptable form of medical management for persons with elevated blood lipids" Dr. Kannel said.
"The available evidence indicates that coronary heart disease appears to result from a combination of contributing factors and that no single factor capable of producing the disease by itself has been convincingly demonstrated", he stated.
"However", he added, "if any common denominator does exist through which such multiple, inter-related factors operate to produce athersclerotic lesions, then some aberration of blood lipids is certainly the chief contender. It appears to be the thread running through the web of circumstances leading to coronary heart disease."
It is clear that 22 years of study had failed to find any connection between dietary cholesterol intake and serum cholesterol levels. The personal wishes of the study director may have suggested otherwise. It is surprising to find that many people still use the Framingham study risk assessment tool to determine future risk.
The UK national policy on statin prescribing is based upon them, according to this verbatim Department of Health statement... "There are a number of different risk assessment tools for coronary heart disease in use in England. Most of them derive from the Framingham prediction equations, which estimate CHD risk based on patients’ age, gender, blood pressure, total cholesterol, high-density cholesterol, presence of diabetes and smoking habit."
When are the authories going to give up on these very poor study conclusions, given as a press statement by Dr Kannel, that were not even related to the facts discovered by the study he was directing? We see in a newspaper publication, the director has categorically stated that there was "NO DISCERNIBLE RELATIONSHIP between reported diet intake and serum choleststerol levels". That finding was after 22 years had elapsed since the initiation of the study and had included 5029 people. Today, we still find people believing in the relationship between dietary cholesterol and heart disease, to the extent that they base the nation policy on its findings.
Professor Grundy was waxing eloquent, in the argument for the wide use of statins. At the end of his article it was hard to avoid the list of statin manufacturers to whom Grundy was a paid consultant. The list is extensive and covers every popular statin preparation. "Merck, Pfizer, Bristol Myers Squibb, and Astra Zeneca" have all paid Grundy for his consultancy services. The reader can guess what sort of sums of money were expended to maintain the multi-billion dollar global statin market.
It is unthinkable that a national policy on statins can be influenced by so-called opinion leaders such as Grundy, when they have been paid by every statin producing pharmaceutical company to say nice things about statins. You can only maintain your professional integrity while you remain independent of all business influences. It makes Grundy's professional opinion, concerning statins, completely worthless and unreliable. I find it risible that he should believe that any rational person would want to heed anything he has to say about statins.
Caveat On ALL Statin Prescribing
posted by Brian Clark on 14 May 2007 at 12:46 amFar from being a "magic bullet" the HMG-CoA reductase inhibitor class of drug is more akin to the charge of a blunderbuss! While the spotlight has been held on their spectacular cholesterol lowering effect other spectacular effects have been cast in shadow, namely the commensurate lowering of ubiquinone, haeme a, dolichol and prenylated proteins.
For example, it is not widely known that haeme a deficiency is analogous to cyanide or carbon monoxide poisoning in its effect on the mitochondria. The ready and widespread acceptance of statins as treatment of choice for hypercholesterolaemia has removed incentive for research focusing on the Lanosterol-Cholesterol pathway, which may very well yield a safer and more readily tolerated treatment.
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