Statins Dont Work

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Why Statins Won't Be Used in 20 YearsTreating the Wrong Cause With the Wrong Drug

"I predict that the statin drug run is about to end, and it will be a hard landing. The thalidomide disaster of the 1950's and the hormone replacement therapy fiasco of the 1990's will pale by comparison to the dramatic rise and fall of the statin industry. I can see the tide slowly turning, and I believe it will eventually crescendo into a tidal wave, but misinformation is remarkably persistent, so it may take years." -Stephanie Seneff

Goals Dietary saturated fat and cholesterol do not cause heart disease Statins don't work well for prevention and their side effects outway their benefit (which is easily achieved in other ways) Statins work by a different mechanism than lowering cholesterol Treatment alternatives

EpidemiologyOf twenty-five prospective studies examining a link between saturated fat and CHD between 1963 and 2005, six (25-30) found an increased risk of CHD with saturated fat intake, though in two of the studies (29, 30), after adjusting for confounders, such as age and smoking, there was no significant association between saturated fat intake and incidence of CHD. The other nineteen (3149) studies found no link between CHD and saturated fat. If we take a close look at the four (25-28) that found a connection, one would increase their risk for heart attack by increasing their saturated fat intake by a mere 0.5 to 1.7 percent of calories. On a 2000 calorie diet, that amounts to 1.1 to 3.8 grams of saturated fat. In the Honolulu Heart Program, the difference between saturated fat intake between those who remained free from CHD and those who died of a heart attack was only half of one gram.

EpidemiologyThe Pukapuka and Tokelau people in the South Pacific have a high saturated fat diet due to coconut intake, but researchers note a complete lack of CVD in these populations despite an average blood cholesterol level of 240 mg/dl in Tokelau (22). The Masai in Africa live on fat-rich milk, meat and blood with an average intake of 300 grams of animal fat daily. Professor George Mann found the Masai to be slim and fit and virtually free of heart disease (23) and despite their very high saturated fat intake, most of them had blood cholesterol levels below 160 mg/dl (24).

Intervention StudiesRose et. al. (51) compared the effect of corn oil, olive oil and saturated fat on CHD. The corn oil group had significantly increased CHD incidents, deaths and total deaths despite the fact that they had a lower blood cholesterol level than the saturated fat group. The olive oil group didnt do much better than the corn oil group. Those in the saturated fat group lived the longest. The DART trial (63) had three different groups; a group that ate more fish, one that lowered fat intake while increasing the ratio of polyunsaturated to saturated fat and a group that ate more cereal fiber. They found no mortality change in the low-fat group, a slight increase in mortality in the fiber group and a significantly lowered mortality in the fish group, despite the fact that blood cholesterol levels went up in the fish group. Recently, the Womens Health Initiative (66) showed no benefit to lowering total fat or saturated fat in the diet in preventing heart disease. In fact, those with existing heart disease were at increased risk for events on the lower fat diet.

Intervention StudiesIn 2006, after examining all the available clinical evidence, Hayward et. al. reported that,current clinical evidence does not demonstrate that titrating lipid therapy to achieve proposed low LDL cholesterol levels is beneficial or safe. (70) Overall, the dietary intervention trials do not support the diet-heart hypothesis. There are more studies showing no correlation between saturated fat and cholesterol intake and heart disease than studies showing a correlation and several studies show a health benefit for saturated fat intake. Those that do show a correlation are flawed or contain too many variables to give us any definite answers.

Modified Lipid HypothesisWe know that people with familial hypercholesterolemia have higher rates of heart disease. We also now know that they have a defective LDL receptor gene so that they have difficulty getting cholesterol from the blood into the cells. That is why they have higher than average blood cholesterol levels. Statin trials have shown that coronary events are reduced even if LDL is not lowered (71-76). In the PROSPER trial, those with the highest LDL cholesterol levels lived the longest (77). In the Japanese Lipid Intervention Trial, the highest death rate was seen among those with cholesterol levels below 160 mg/dl. The lowest overall mortality rate was seen in those who had blood cholesterol levels between 200-259 mg/dl and LDL between 120-159 mg/dl. In humans, 20 mg/day for 9 days of atorvastatin administration reduced oxidized LDL, but did not reduce blood levels of LDL (78).

Modified Lipid HypothesisBased on the evidence, statins appear to exert a positive effect on CHD through some other mechanism besides cholesterol lowering which would imply that the lipid hypothesis is incorrect in its present form. It appears that the presence of oxidized LDL is more important than the amount of cholesterol in the blood.

Proposed Model for Heart DiseaseLDL receptors normally receive LDL particles and remove them from circulation so that they can deliver nutrients and cholesterol to cells, and fulfill their normal roles in the body. If LDL receptor activity is downregulated, LDL particles clear more slowly from and spend more time in the blood. Particles accumulate. When LDL particles hang out in the blood for longer stretches of time, their fragile polyunsaturated fatty membranes are exposed to more oxidative forces, like inflammation, and their limited store of protective antioxidants can deplete. When this happens, the LDL particles oxidize. Once oxidized, LDL particles are taken up by the endothelium a layer of cells that lines the inside of blood vessels to form atherosclerotic plaque so they dont damage the blood vessel. This sounds bad (and is), but its preferable to acutely damaging the blood vessels right away. So its the oxidized LDL that gets taken up into the endothelium and precipitates the formation of atherosclerotic plaque, rather than regular LDL. OxLDL, poor receptor activity, and inflammation are the problems.

Evidence for the modified lipid hypothesisThe component of LDL that is the most likely to become oxidized is the polyunsaturated fatty acids (PUFA). LDL from people who consume more PUFA from vegetable and fish oils oxidizes more easily and vitamin E does not help to minimize that oxidation (84). It is the linoleic acid component of oxidized LDL that leads to atherogenesis (85). A 2004 study by Mozaffarian et. al. showed that postmenopausal women who ate more PUFA, had worsening atherosclerosis over time, but for those who ate more saturated fat, the less their atherosclerosis progressed. In the highest intake of saturated fat, atherosclerosis actually reversed over time (86). Herron et. al., in 2004, noted that a high cholesterol diet protects LDL from becoming oxidized (87) and yet another study showed egg consumption to be protective of LDL (88). Milk fat has also been shown to be negatively associated with CVD (89, 90). Polyunsaturated fats have also been shown to increase cancer risk (91-93) and to play a role in acute respiratory distress syndrome (94). Antioxidants have been shown to protect LDL from oxidation (95-96).

Statins are ineffectiveIn primary prevention, statins do not reduce the risk of death [2] In predominantly primary prevention, in women of any age, there is no reduced risk of cardiovascular events with statin treatment [3]. This is also true for men aged 70 or over [3]. In high-risk men aged 30-69 years, about 50 patients need to be treated for 5 years to prevent one cardiovascular event [3].1. Dorresteijn JA, Aspirin for primary prevention of vascular events in women: individualized prediction of treatment effects. Eur Heart J 16 November 2011 [Epub ahead of print] 2. Ray KK, et at. 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 3. Abramson J, et al. Are lipid-lowering guidelines evidence-based? The Lancet 2007:369:168-169

Statins dont increase survival in healthy people

Statins have never been shown to be effective in reducing the risk of death in people with no history of heart disease. No study of statins on this primary prevention population has ever shown reduced mortality in healthy men and women with only an elevated serum cholesterol level and no known coronary heart disease. (CMAJ. 2005 Nov 8;173(10):1207; author reply 1210.) In fact, an analysis of large, controlled trials prior to 2000 found that long-term use of statins for primary prevention of CHD produced a 1% greater risk of death over 10 years compared to placebo

Statins dont increase survival in women

Despite the fact that around half of the millions of statin prescriptions written each year are handed to female patients, these drugs show no overall mortality benefit regardless of whether they are used for primary prevention (women with no history of heart disease) or secondary prevention (women with pre-existing heart disease). In women without coronary heart disease (CHD), statins fail to lower both CHD and overall mortality, while in women with CHD, statins do lower CHD mortality but increase the risk of death from other causes, leaving overall mortality unchanged. (JAMA study)

Statins dont increase survival in the elderly

The only statin study dealing exclusively with seniors, the PROSPER trial, found that pravastatin did reduce the incid