Should We Put Statins in the Drinking Water?

Summarized by Robert W. Griffith, MD
May 19, 2004

What statins can do

Anyone keeping track of health matters knows that statin drugs can reduce the occurrence of heart attacks, stroke, and several other cardiovascular diseases (e.g. heart rhythm disturbances, peripheral artery disease). And recent reports indicate that these drugs may also possibly reduce the risk of age-related macular degeneration (AMD), osteoporosis, multiple sclerosis (MS), Alzheimer's disease, and cancer.

Although they were originally designed, tested, and approved for reducing low-density lipoprotein (LDL) cholesterol levels, several studies have demonstrated that the benefits of statins extend beyond their ability to lower LDL cholesterol. Physicians think that these drugs have a general anti-inflammatory action that's responsible for these effects 'above-and-beyond' cholesterol-lowering.

Effects of more intensive statin treatment

It may be that we are only at the beginning of exploring the benefits of statins. A new study has just been published that compares the results obtained with two different statins that were dosed so that one group of patients (pravastatin 40 mg daily) had a moderate lowering of LDL cholesterol, whereas the other group (atorvastatin 80 mg daily) had a profound reduction.¹ The progression of coronary atherosclerosis was followed by ultrasound; it was found that the patients who had the more intensive lowering of LDL cholesterol had a greater reduction in their coronary atheroma.

In a different study, but one using the same drugs at the same dose levels, the drug that lowered LDL cholesterol more - atorvastatin - resulted in a 16% reduction in major cardiovascular events (heart attack, angina, heart failure) and a 28% reduction in death from all causes over 2 years, compared with the other drug - pravastatin.² Moreover, the superior benefits of intensive cholesterol lowering appeared very soon, within the first 30 days of treatment.

Why is one statin better than another?

Researchers aren't sure what made the difference between the results for atorvastatin and pravastatin. Atorvastatin is lipophilic (i.e. it dissolves in fat and can cross cell membranes very easily), whereas pravastatin is water-soluble, and less widely distributed in the body.

Because lowering LDL cholesterol is associated with anti-inflammatory effects, the studies measured the C-reactive protein (CRP) levels in the patients; CRP is a marker for inflammatory processes in the body. In the first study, where coronary artery disease was stable, CRP was decreased 36% by atorvastatin and by 5% with pravastatin. In the second study, where patients had acute cardiac ischemia (lack of oxygen reaching the heart muscle), CRP was lowered equally by both drugs. So anti-inflammatory activity doesn't seem to explain the difference in action of the two drugs.

What does this mean?

Up to now it's been thought it was optimal to lower LDL cholesterol to 100 mg/dL (2.6 mmol/L). But the new study results change that view completely. It's been calculated that only about 1 in 3 people in the USA who meet the requirements for being treated with statins do, in fact, receive them. At present, statins are very expensive, and increasing the dose to achieve the results obtained in these studies would make the cost factor much worse. However, they are quite safe; in Britain, one statin has been approved for over-the-counter sale.

Apart from the need to dose statins more effectively, these studies have revealed an important error in the accepted view, namely that drugs from the same class (e.g. 'statins', 'antihistamines') have no great differences in their activities. These head-to-head comparisons of two statins show that all drugs in the same class are not created equal, and require studies like this to help determine the pros and cons of individual treatments. Just to make the point: such a study with a new statin - rosuvastatin - shows it to be superior to atorvastatin in lowering LDL- and raising HDL-cholesterol.³

It looks as if the right way to dose statins is to monitor the LDL cholesterol and CRP levels, and increase the dose until 'satisfactory' levels of these markers are reached; the difficulty now is deciding what levels are considered satisfactory!

Source

• Intensive statin therapy - a sea change in cardiovascular prevention. EJ Topol, N Engl J Med, 2004, vol. 350, pp. 1562--1564

Footnotes
1. Effect of intensive compared with moderate lipid-lowering therapy on the progression of coronary atherosclerosis: a randomized controlled trial. SE Nissen, EM Tuizcu, P Schoenhagen, JAMA, 2004, vol. 291, pp. 1071--1080
2. Comparison of intensive and moderate lipid lowering with statins following acute coronary syndrome. CP Cannon, E Braunwald, CH McCabe, N Engl J Med, 2004, vol. 350, pp. 1495--1504
3. Comparison of rosuvastatin versus atorvastatin in patients with heterozygous familial hypercholesterolemia. EA Stein, K Strutt, H Southworth, Am J Cardiol, 2003, vol. 92, pp. 1287--1293

Related Links
Treating Your Raised Cholesterol Level
Statins Work Even When the Cholesterol Isn't Raised
Should CRP Testing be Routine?

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