Sergio Fazio and MacRae F Linton
Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

Current Controlled Trials in Cardiovascular Medicine 2001, 2:8-11


The importance of low-density lipoprotein (LDL) control in the management of patients at high risk of cardiovascular events is unquestionable. The major statin trials have shown that the benefits of LDL lowering extend throughout the range of risk and the range of serum cholesterol, and have indicated that the protective effects of the intervention are mostly related to the baseline risk. Statin therapy is, for this reason, currently seen as an anti-atherogenic approach for the majority of high risk individuals and possibly all coronary heart disease patients. This debate is not about the value of statin therapy or the importance of LDL reduction, but about the goals to be set once we decide that LDL cholesterol must be reduced. With the National Cholesterol Education Program (NCEP) guidelines representing a solid middle ground, the two viewpoints in this debate try to argue, on one hand, that the LDL goals should be substantially lower than our current standards or, on the other, that a specific on-treatment LDL value may not be the most important goal to pursue. We defend the latter position by presenting the case that the most effective LDL intervention in high risk patients is to achieve a reduction of at least 30%. This 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.

Keywords: atherosclerosis, clinical trials, coronary disease prevention, coronary heart disease risk, low-density lipoprotein cholesterol, meta-analyses, statins


In a debate to discuss whether LDL cholesterol should be decreased to very low levels to achieve optimal cardiovascular risk reduction, the viewpoint defending aggressive intervention is usually considered the most logical stance and is by far the most popular position. We defend the opposite viewpoint in this paper; that is, not all high risk patients should have the objective to reach a low LDL concentration (defined as any prespecified number substantially lower than 130 or 100 mg/dl). We will present, in this brief discussion, the case that the most important lipid maneuver in high risk patients with inappropriate LDL is a significant reduction from baseline (approximately 30-40%), rather than the attainment of a specific on-treatment level. Not only is this approach largely in agreement with the goals set by the NCEP guidelines [1], as it drives the majority of high risk patients to a LDL level of less than 130 or 100 mg/dl, but it is even more aggressive than the guidelines for the high risk patients with low baseline LDL (130 mg/dl or lower). For the small population of high risk patients with high baseline LDL (200 mg/dl and higher), debating on the appropriate lipid goal is a frivolous exercise because the high prevalence of genetic dyslipidemias in this group attenuates the response to treatment. The most reasonable position is to accept the results of high dose lipid-lowering therapy, whether achieved with a single drug or a combination regimen when necessary.