New guidelines urge patients to keep to even lower cholesterol levels than before
With the recent release of updated guidelines on cholesterol management, one can't help but question whether there really is a lower limit of LDL-C levelsthat point at which further lowering no longer exerts preventive benefits. So far, the number has decreased steadily from 160 mg/dl, to 100 mg/ dl, and, most recently, to 70 mg/dl in very high risk patients. The latest recommendation comes from an update to the 2001 guidelines from The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program (NCEP).
Published in the July 13 issue of Circulation, the document is an outgrowth of five major clinical trials that focused on the effect of HMG-CoA reductase inhibitors (statins) on cardiovascular outcomes. What makes this evidence newsworthy is the fact that when the guidelines were originally released in 2001, recommendations were based on multiple studies carried out with therapies other than statins. This latest evidence confirms the role of LDL-C as a major risk factor in coronary heart disease (CHD), establishes the effectiveness of statins in preventing cardiovascular events, and sets new goals for lowering LDL-C.
"Since their introduction, the statins have evolved from simple lipid treatment to mainstay preventive therapy in patients whose comorbidities, such as diabetes, predictably lead to coronary events," noted Sateesh Maharaj, R.Ph., staff pharmacist at Newark (N.J.) Beth Israel Medical Center. Results of recent trials support inclusion of diabetes patients in the high-risk category and confirm the benefits of LDL-lowering in diabetic and older patients.
The major change in the guidelines revolves around the management of high-risk patients, who are defined as those having either CHD or CHD risk equivalents (peripheral arterial disease, abdominal aortic aneurysm, carotid artery disease, diabetes, and two or more risk factors with 10-year risk for myocardial infarction or CHD-related death > 20%). The recommended LDL-C goal for these individuals is < 100 mg/dl, and when the risk is especially high, an LDL-C goal of < 70 mg/dl is a therapeutic option. "The lower the better for high-risk peoplethat's the message on LDL-C from recent trials," noted Scott Grundy, M.D., Ph.D., the American Heart Association's representative to the NCEP and chair of ATP III.
High-risk patients who also have high triglycerides or low HDL-C levels should be treated with a combination of an LDL-C-lowering agent (statin) and a fibrate or nicotinic acid. Although the evidence base surrounding fibrates is not as strong as that for statins, a post hoc analysis of several trials indicates that fibrates do reduce the risk of CHD events in patients with high triglycerides and low HDL-C. As a result, the guidelines have carved out an adjunctive role for fibrates in combination with statins.
"This regimen, however, increases the risk of myopathy and rhabdomyolysis," warned Maharaj. According to the guidelines, concern over development of these complications has been alleviated somewhat by the recent finding that fenofibrate does not interfere with catabolism of statins and, therefore, may not substantially increase the risk of clinical myopathy in patients treated with moderate doses of statins. The use of nicotinic acid in raising HDL-C is supported by several clinical trials showing that, when used with a statin, the agent produces a marked reduction in LDL-C and a striking rise in HDL-C.
For moderately high risk persons, the recommended LDL-C goal is < 130 mg/dl, but an LDL-C goal of < 100 mg/dl remains a reasonable option as well. The latter goal also applies to moderately high risk individuals with a baseline LDL-C of 100 to 129 mg/dl. When treating high-risk or moderately high risk patients, the guidelines advise that intensity of therapy be sufficient to achieve at least a 30%-40% reduction in LDL-C levels. This goal can be accomplished by using standard doses of statins (see table) or combining lower doses of statins with other drugs or productse.g., nicotinic acid, ezetimibe (Zetia, Schering-Plough), plant stanols/sterols.
"These new guidelines will require mass reeducation of physicians and patientsa situation that strengthens the case for pharmacist-driven disease management," noted Maharaj. "After all, we're the only ones who come into contact with all three major playersthe Rxs, the patients, and the physicians," he added.
Elena Beyzarov. New guidelines set ambitious goals for lowering cholesterol.
Aug. 9, 2004;148:10.