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Lipid management in primary and secondary prevention reduces cardiovascular morbidity and mortality. Lowering of low-density lipoprotein cholesterol (LDL-C) levels with statins remains the primary goal of therapy. For secondary prevention patients, those with coronary heart disease (CHD) or CHD risk equivalents, intensive LDL-C lowering is recommended, although the precise target value is still debated. For primary prevention, reduction in LDL-C levels is based on patient risk for CHD. In clinical outcome trials to date, statins benefit those who are at moderate to high risk and appear to have less clinical benefit for those at low risk. Yet despite aggressive LDL-C management with statins, there remains a residual risk for CHD events in high-risk patients. Secondary targets have been proposed to decrease this risk, including non–high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and apolipoprotein B, as well as other emerging targets, including LDL particle number and lipoprotein(a). In many high-risk patients, statin monotherapy is unlikely to achieve goals, and combination therapy with other agents is a safe, effective, and optimal therapeutic approach.