Personalized Medicine Approach Provides More Benefit for Patients with High Cholesterol than Current Guidelines

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Statins are a class of drugs that lower cholesterol and thereby reduce the risk of heart disease and stroke. They work by preventing the synthesis of low-density lipoprotein (LDL or “bad cholesterol”) in the liver and promoting its clearance from the blood. They are the most effective cholesterol-lowering drugs currently available and are the cornerstone of the National Heart, Lung, and Blood Institute’s National Cholesterol Education Program (NCEP) treatment guidelines.

The NCEP recommends a “treat-to-target” strategy, in which patients are given specific statin doses to achieve a desired level of LDL cholesterol in the blood. In this case, low LDL cholesterol is the “target.” Yet some physicians are questioning whether treating to any target is the best approach to fighting disease. A recent study in the Annals of Internal Medicine suggests that “tailored treatment”, an approach attempts to practice personalized medicine by estimating three factors, is more effective than a treat-to-target strategy [1].

HDL and LDL Cholesterol

Researchers examined how a simple tailored treatment compared with a treat-to-target strategy based on NCEP treatment guidelines. They used data from the National Health and Nutrition Examination Survey (conducted from 1988 to 1994) and computationally augmented 4,503 patients between the ages of 30 and 75 who had never been treated with statins and had no history of heart attack to create a simulated population of 1 million. They then estimated each person’s risk for fatal and non-fatal coronary artery disease, and examined the benefits achieved by using a 5-year treatment period. The treat-to-target strategy was based on NCEP guidelines, which includes an optional, more intensive medication regimen (40mg instead of 20mg of simvastatin, a moderate dose-potency statin, and then a potential switch to atorvastatin, a high does-potency statin) for patients at higher risk for coronary artery disease. Both this intensive approach and the standard treat-to-target options were considered In the tailored treatment approach, patients with a 5 — 15% risk of coronary artery disease over 5 years received 40mg simvastatin and those with a risk greater than 15% received 40mg atorvastatin. As in all modeling studies, they made a number of simplifying assumptions: first, that the only thing statins do in the body is reduce LDL cholesterol; and second, that a change in a patient’s LDL cholesterol level is a perfect measure of his or her coronary artery disease risk reduction. The researchers write:

We realize that the first assumption is controversial and that the second assumption is untrue (LDL cholesterol determinations have substantial measurement error), but these assumptions allow us to test the hypothesis that tailored treatment is an inherently superior strategy, even under circumstances most favorable for a treat-to-target strategy.

In calculating the risk factors in their simulated population and analyzing the data from their modeling studies they used a “risk stratified” analysis. This is not how clinical trials are usually analyzed, but it reveals the different benefits and harms accrued by groups of patients with higher and lower risk of disease rather than calculating the average benefit among all of the people in the trial [2]. The researchers found that after five years, tailored treatment prevented significantly more coronary artery disease, saved more lives, treated fewer people overall and treated a smaller percentage of the population with more aggressive treatment. This was the case even with their assumptions biased toward the treat-to-target approach. In their simulated population they identified a group who would receive 40mg simvastatin under tailored treatment but nothing under NCEP guidelines; this group had relatively low LDL levels but high coronary artery disease risk. In contrast, a group who would get 40mg simvastatin under NCEP guidelines but nothing with tailored treatment, had high LDL levels but low overall risk. Tailored treatment could thus spare this patient population unnecessary side effects and expense.

Heart disease, like most complex biological processes, is impacted by a number of factors. These include age, genetics, smoking status, blood pressure and cholesterol levels. None can be considered in isolation. When choosing the best treatment, three things should be considered: the patient’s risk of disease without treatment, the potential benefit of the treatment and the potential harm of the treatment. This study demonstrates that a personalized medicine approach, tailored treatment, provides more benefit per person treated and prevented significantly more coronary artery disease morbidity and death than the currently recommended treat-to-target approaches.

For more information, visit the MedlinePlus interactive tutorial on Managing Cholesterol. The presentation will help you understand what cholesterol is and how to control the level of cholesterol in your body.


  1. Hayward et al. Optimizing statin treatment for primary prevention of coronary artery disease. Ann Intern Med. 2010 Jan 19;152(2):69-77.
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  2. Hayward et al. Reporting clinical trial results to inform providers, payers, and consumers. Health Aff (Millwood). 2005 Nov-Dec;24(6):1571-81.
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  3. Cziraky et al. Targeting low HDL-cholesterol to decrease residual cardiovascular risk in the managed care setting. J Manag Care Pharm. 2008 Oct;14(8 Suppl):S3-28; quiz S30-1.
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  4. Zulman et al. The relative merits of population-based and targeted prevention strategies. Milbank Q. 2008 Dec;86(4):557-80.
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About the Author

Diana Gitig, Ph.D., is a freelance science write based in White Plains, New York. She earned her Ph.D. in Cell Biology and Genetics from Cornell University's Graduate School of Medical Sciences.