Why is there surprise at the new 4year international study (in NEJM of 3 April 2008 http://content.nejm.org/cgi/content/abstract/358/14/1431 ) that further 26% lowering of average “bad” low density cholesterol LDLC – level (and CRP c-reactive protein) by adding a new designer drug for 2 years to a statin alone makes no further difference to vascular or all-cause outcome? In fact in even this young population there were 46% more cardiovascular CVD events on the statin – ezetimibe combination (10/357 = 1.4%pa) than on simvastatin alone (7/363 = 0.96%pa).
At baseline the subjects at a mean age of 46+- 10yrs (half men) were an average of about 10kg overweight; 28% smoked, only 16.4% were already hypertensive, but 80% already on statins (they had to have had a total cholesterol TC of >5.43mmol/L off lipid-improving drugs – their mean TC off drugs was 10.4mmol). Other than the 5% who had already had heart attack, and perhaps the 2% who were diabetic, why were these average mostly well young people targeted for further cholesterol lowering, when their mean TC was already down to 6.9mmol/L on statin (vs 5.7 on the twin drugs) with HDL 1.2 ? when all they needed to do was lose a few kg fat by sensible eating and exercise, stop smoking and take some safe fat-reducing anti- atheroma antioxidant and insulin-sensitising supplements including fish oil? Why should lowering of blood markers already within the average range give any benefit as opposed to doing harm? According to Sijbrands (BMJ 2001) from Erasmus University http://www.bibalex.org/Supercourse/lecture/lec3191/001.htm, such a cohort of people untreated has a standardized mortality ratio of 1.88- but in this new 2008 Enhance paper, their mortality rate on statin alone was already so low (CVD mortality 0.1%pa) that all-cause mortality was not even mentioned.
So it should be asked why such a trial was undertaken, when there has never been any evidence that drug lowering of mild to moderate TC (ie below 8mmol/L) or LDLC lowers non-CVD morbidity and mortality? – and when there are legion proven supplements that lower morbidity and mortality ? The evidence against cholesterol lowering in those without high CVD risk was already shown over a decade ago by the Sheffield team (Haq 1995), who have consistently stressed that “cholesterol measurement by itself is not a good way to identify those with high coronary risk”, and that there is little advantage (except for anti-cholesterol practitioners and laboratories) in lowering average cholesterol levels unless CVD risk is at least 2% if not 3% a year. The CVD risk of this Enhance trial cohort on statin was only 1% a year.
No statin trial has ever shown that these lipid-lowering drugs drugs lower or even address non-vascular disease or mortality; whereas (except in those at the highest cardiovascular risk) nonvascular degenerative disease is by far the bigger burden in later years. Dr James le Fanu summarised the evidence against universal cholesterol-lowering in mild-to-moderate lipidemia already in The Rise and Fall of Modern Medicine (Abacus UK 1999).
Since according to the lipid-lowering industry, most of us overweight older folk naturally have risky lipid levels to be targeted by zealous drug marketers and prescribers, some British doctors who know better have actually invested heavily in promoting (without evidence of global benefit :risk) a farcial polypill including a statin, an antihypertensive and aspirin for all. http://www.bmj.com/cgi/content/full/326/7404/1419
It is common cause that after 30 years of widespread use, statins do nothing for overweight, insulin resistance, hyperglycemia, other CVD factors, nor for other major degenerative diseases of overweight and aging – infection, osteoporosis, cancer, arthritis, sexual dysfunction – and thus do nothing to lower non-vascular morbidity and mortality. But statins do cause widespread insidious fatigue, myalgia, depression, impotence; and now lung and tendon rupture complications, let alone hepatorenal problems- are being increasingly reported.
By contrast, it is common cause from both trials and observational studies for >30years that APPROPRIATE
1) metformin for overweight/ lipidemia; 2) fish oil; 3) combined hormone replacement; and 4) blend of the other proven >60 supplements (~15 vitamins, ~10 minerals, and the >35 biologicals including herbs), each reduce all-cause morbidity and mortality by one-third to half. Together, the combination is impressively effective in daily practice in the most desperately ill patients already on maximum conventional prescription modern drugs for osteoporosis, arthritis, CVD, type 2 diabetes on insulin with crippling neuropathy etc.
Such is the insidious influence of the global drug industry via Regulators (Elaine Feuer Innocent Casualties: The Fda’s War Against Humanity USA 1996), that we physicians are threatened with prosecution by our own medical defence advisor if we do fair comparative marketing, promote that appropriate well-proven old drugs- the natural micronutrients which drug companies prudently refuse to sponsor to be tested against modern patented prescription drugs – are better for both prevention and treatment of chronic degenerative diseases of aging than the imitator modern wannabe patentable designer drugs that attempt to mimic the original natural drugs- vitamins, minerals, biologicals – evolved and proven over millennia.
We are even threatened with prosecution for using metformin for prevention of diabetes and lipidemia, when it is the only patent drug that has ever been tested in a 20year RCT (Holman ea the UKPDS 1998), and proven to halve all-cause mortality over 5 years in type 2 diabetics, and it halves the incidence of new diabetes in overweight people with metabolic syndrome risks; whereas in trials, sulphonylureas – like all other modern patent designer drugs – had no benefit on all-cause mortality or on decreasing new diabetes incidence in older adults.
Haq IU, Jackson PR, Ramsay LE ea Royal Hallamshire Hospital, Sheffield, UK Sheffield risk and treatment table for cholesterol lowering for primary prevention of coronary heart disease. Lancet. 1995;346:1467-71 http://www.ncbi.nlm.nih.gov/pubmed/7490996 and Prediction of coronary risk for primary prevention of coronary heart disease: a comparison of methods QJM. 1999 ;92:379-85. http://qjmed.oxfordjournals.org/cgi/content/abstract/92/7/379
J.P. Kastelein ea, for the ENHANCE Investigators http://content.nejm.org/cgi/content/short/NEJMoa0800742 NEJM 3 Feb 2008: 358:1431-1443 Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia