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Clinical Corner

This Editorial has been written by the specialist opinion leader, Professor Ted Ganiats, University of California, San Diego, California and published in the latest issue of the serial publication, Drugs in Context.

For more information, you can download a free-of-charge Quick Reference Guide to the Atorvastatin in Lipid Disorders issue of Drugs in Context which is designed to give you an insight into the numerous key points of information and practical guidance contained in each issue, via carefully selected quotations taken directly from each part of the publication.

CSF Medical Communications publishes Drugs in Context which aims to provide clinicians around the world with a comprehensive, authoritative and independent review of all the significant data on a specific drug, placed in the context of the disease area and today's clinical practice. Each issue comprises four parts - an opening Editorial, a Disease Overview, a Drug Review and finally an Improving Practice section. Each drug is placed within the context of its indications and the clinical practice situation concerned.

I have a love-hate relationship with the statins. Cardiovascular disease is epidemic in the USA. It is the number one cause of death in both women and men, and its cost, in terms of morbidity, mortality, and dollars, is truly staggering. As a physician, I feel compelled (appropriately) to do something. It is my duty. In my goal to find a tool to fight this killer, statins seem almost perfect because they strike at the 'heart' of the matter.

At one level, there are many causes of cardiovascular disease. Dyslipidemia is a major factor, with low density lipoprotein cholesterol (LDL-C) holding the current limelight as the major culprit. This is a little confusing, since LDL-C by itself, accounts for less than half the cardiovascular disease, and an alphabet soup of lipid-related molecules (high density lipoprotein cholesterol [HDL-C], triglycerides, fractions of LDL and lipoprotein [Lp] a etc.) all appear to play at least some role. The endothelium - the site of atherosclerosis - plays a role, of course, perhaps mediated by endothelial functioning. The supposed importance of inflammation is growing, whether measured simply (C-reactive protein) or through more complex tests.

One beauty of the statins is that they lower LDL-C, improve endothelial functioning and reduce inflammation. There is also a plethora of randomized trials showing statins reduce the risk of heart disease and, in high-risk individuals, actually improve all-cause mortality. This is done with relative safety; most consider the statin risk profile to be acceptable.

Of all the statins, atorvastatin is especially attractive. This issue of Drugs in Context highlights many reasons, but simply put, of all the statins that have been on the market for a few years, it is able to provide the best LDL-C lowering.

So, pop a pill, hit the cause and reduce cardiovascular disease - a dream for both clinicians and patients!

Or is it? Multiple risk factors contribute to cardiovascular disease. Some of these factors are inherent (e.g. age, gender and family history) and some are 'modifiable' (though at times they are quite difficult to modify). Modifiable risk factors may be related to behavior (e.g. low physical activity, smoking and atherogenic diet), physiology (e.g. secondary hypertension) or a combination of factors (e.g. the metabolic syndrome).

The problem, of course, is that having an 'almost perfect' drug like a statin promotes a strange transformation. Instead of the drug being an important treatment of the disease, the drug becomes the treatment; the disease and drug become synonymous. We have already seen this; for many clinicians, cardiovascular disease is a disease of cholesterol metabolism, and this can be best treated with statin. A recent editorial in this series notes: "the best plan is to place substantial reductions in LDL-C levels at the core of coronary heart disease prevention strategy."

However, this strategy is unfortunate for several reasons. First, of course, the clinician may not be appropriately aggressive in addressing other factors that significantly contribute to cardiovascular health (e.g. smoking, hypertension and diabetes). Second, the patient may not appropriately address other factors that contribute significantly to cardiovascular health. More than one of my patients has sighed in relief when told that her cholesterol was normal, even though she smoked and had a bad diet, high-risk family history and hypertension.

It can be argued that given limited physician time and limited patient motivation for behavioral change, the 'statin first' approach makes sense. By giving a statin to all patients that have high LDL-C we make the most efficient use of the provider's time in reducing cardiovascular disease. I have no doubt that this is true in many practices. However, the reduction of cardiovascular disease is not my goal; my goal is the overall health of my patients. To that end, the National Cholesterol Education Program (NCEP), via the third report of the Adult Treatment Panel (ATP 3) promotes lifestyle modification as the first step for all patients with dyslipidemia. This healthier lifestyle has the benefit of not only reducing cardiovascular disease but also the risks of cancer, diabetes and lung disease. A patient who approaches cardiovascular disease as a defect in cholesterol metabolism will benefit from statins. The patient who approaches the disease as having many causes will achieve a wide range of health benefits.

My love-hate relationship with statins stems from the focus it promotes in physicians and patients. Cardiovascular disease is bad, and statins are a wonderful choice in the treatment of this disease. However, if our goal is the overall health of our patients, we should continue to push lifestyle modification as an essential element of its treatment. To be sure, research is needed to help the busy clinician develop systems to help patients more with lifestyle modification, but we must not let the effectiveness of statins blind us to the benefits of a healthy lifestyle.