To state it simply, the proponents of aggressively low LDL goals would like to see every high risk patient reach a LDL level of 70-90 mg/dl. This position is flawed for the following reasons. First, many high risk patients with severe hypercholesterolemia (LDL level >200 mg/dl) will not be able to reach that goal even at the highest doses of more than one lipid-lowering agent. Setting unreasonable, nonevidence-based goals will affect patient compliance, the ultimate objective to make an impact on CHD risk.
Second, the cyclical variations in LDL induce oscillations whose range often encompasses a predefined goal in high risk patients with moderate hypercholesterolemia, thus triggering unjustified dose adjustments or changes of drug. Finally, the high risk patients without hypercholesterolemia (LDL level <100 mg/dl) may be denied LDL lowering intervention because they are already 'at goal'. Our position is also simple, but has the additional advantages of being feasible throughout the range of cholesterol distributions and being completely based on published clinical evidence. We support the concept that the most effective LDL intervention in high risk patients is to achieve a reduction of at least 30%. This concept is based on the knowledge that atherosclerosis initiation and progression depend on plasma cholesterol, and that the vast majority of LDL concentrations in western populations are sufficient to support plaque formation in the appropriate 'permissive' environment. Our strategy complies with the NCEP guidelines, as most of the high risk patients treated with an average dose of an average statin would experience a 30-40% LDL reduction that would put on-treatment LDL levels safely below goal. Our position differs from both the guidelines and the proponents of more aggressive LDL goals in the management of the two extremes of the cholesterol distribution, where our lack of interest in a predefined on-treatment LDL concentration would make us more aggressive than guidelines on low baseline LDL patients and less aggressive than guidelines on high baseline LDL patients.
Conclusion
If, at the end of this discussion, the two positions seem to have more similarities than differences, it is because they do. The controversy on which to set LDL goals in high risk patients is actually not a burning social or clinical issue, as little disagreement exists on the value of LDL lowering in high risk patients, and therapy is commonly limited to the use of one statin or another. Different statins at different doses provide, overall, a narrow range of LDL reductions accompanied with significant variation in individual responses, so that different philosophical viewpoints are not easily translated into different practical stances.
The greatest difference between the two viewpoints is in the use of cholesterol lowering as a means to reduce cardiovascular disease in the population. The proponents of aggressive LDL lowering intend to eradicate atherosclerosis by acting on its initiating factor, with the assumption that adequately low LDL levels will impede lesion growth in most individuals, irrespective of their underlying risk profile. We consider cholesterol lowering as one of the many battles in the war on atherosclerotic disease, a war that will not be won without a concerted attack against the other major players in the enemy camp, including inactive lifestyle, the western diet, obesity, cigarette smoking, diabetes, and hypertension.
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Acknoweldgements
SF and MFL are Established Investigators of the American Heart Association, and are supported by National Institutes of Health grants HL57986, HL53989, HL65709, and HL65405.
Sergio Fazio1 and MacRae F Linton2
Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
1Email: SERGIO.FAZIO@VANDERBILT.ED, 2macrae.linton@vanderbilt.edu
Current Controlled Trials in Cardiovascular Medicine 2001, 2:8-11 doi:10.1186/cvm-2-1-008
The electronic version of this article is the complete one and can be found online at: http://cvm.controlled-trials.com/content/2/1/008
© 2001 Fazio and Linton; licensee BioMed Central Ltd. Verbatim copying and redistribution of this article are permitted in any medium for any purpose, provided this notice is preserved along with the article's original URL.
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