Drugs

Statins

The concept of high blood cholesterol as a major cause of atherosclerosis is based on observations of severe early atherosclerosis in patients with congenital absence of LDL receptors in the liver so that blood cholesterol levels are very elevated. Brown and Goldstein received the Nobel Prize in 1985 for the discovery of these receptors. Fortunately, 99.99% of atherosclerosis is not due to a deficiency of these receptors but due to lifestyle which can easily be changed.

In 1987 the first statin, Mevacor, was licensed in the USA. If statins were the cure for atherosclerosis, one would think that atherosclerosis would have disappeared shortly thereafter. On the contrary mortality from atherosclerosis had been decreasing slowly since the late 1960's and showed no dramatic decrease with the introduction of statins. The only thing that changed was a marked increase in the incidence of obesity and diabetes caused by the moral hazard effect of statins, their most serious side effect.

When lookiing at blinded, controlled trials of statins a number of points have to be considered:

1. Are the subjects eating a non-atherogenic diet. We now know that diet has a huge effect on atherosclerosis? Unless we can be assured that all subjects in the trial are eating a non-atherogenic diet and are moniored continuously for adherence to it, the study has no relevance to clinical practice. Subjects in the WOSCOPS and ASCOT-LLA trials never were instructed in non-atherogenic diets and monitored for adherence to the diets. Studies that fail to do so are clearly unethical.

2. Is the study in done for "primary" prevention or "secondary" prevention? The 4S study is often quoted as showing decreased morality with statins. There is often no mention that 4S was a secondary prevention trial. The subjects all had symptomatic atherosclerosis. This trial has no applcation to the vast majority of the population. Primary prevention trials like WOSCOPS or ASCOT-LLA trials show no mortality benefit. At least 90% of statin prescriptions are given for primary prevention. But the Therapeutic Initiatives Group at the University of British Columbia, which has no connection with the drug industry, has stated categorically that " ...statins have not been shown to provide an overall health benefit in primary prevention trials." Their conclusion was recently given support by a trial of Lipitor, the most prescribed drug in the world, in primary prevention iin people with a high coronary artery calcium volume, a crude measure of plaque volume. Even high dose Lipitor had absolutely no effect in halting the progression of plaque. Patients who have had a heart attack may represent a special group which has declared itself by plaque rupture. Statins may have a small effect in this group which is independent of blood cholesterol.

3. Has the trial considered the differences between the sexes? A meta-analysis of many statin trials has concluded that "For women without cardiovascular disease, lipid lowering does not affect total or CHD mortality. Lipid lowering may reduce CHD events, but current evidence is insufficient to determine this conclusively".

4. Statins, llike drugs for hypertension and Type 2 diabetes do not treat disease but generally serve only to partially counteract lifestyle insults to body and make the numbers (cholesterol, blood pressure, blood glucose) look better. They are not analogous to antibiotics or hormone replacements. All statin trials have been blinded; subjects did not know if they were taking the drug or a placebo and therefore had no incentive to change lifestyle. When statins are available to the general population it is implied that they will prevent heart attacks and people have less incentive to change lifestyle or even adopt a more atherogenic, obesogenic lifestyle - the moral hazard side-effect of statins. Thus the pandemic if obesity and Type 2 diabetes.

Drugs

Statins

Here is what the World Health Organization has to say about statins