Treatment challenges in hypercholesterolemia

Primary and secondary prevention trials in individuals with high plasma cholesterol levels have proven that cholesterol-lowering drug treatment significantly reduces the risk of coronary heart disease (CHD) morbidity and mortality, and prolongs life. The degree of clinical benefit derived from such treatment appears to be proportional to the percentage reduction in plasma cholesterol. Regression and reduced progression of atherosclerosis may partially account for the clinical gains derived from lipid-lowering drug therapy; however, other direct mechanisms may be operative, including reduced atherogenicity of macrophages, improved vascular vasodilation, and reduced thrombogenesis. Specific treatment is determined on the basis of LDL cholesterol levels and overall global risk for CHD, that is, the presence of CHD and/or other CHD risk factors. Angiographic and clinical data support intensive lipid-lowering therapy in all hypercholesterolemic patients with CHD and those with high CHD risk, particularly those with ultrasonographic evidence (but no symptoms) or clinical signs of extracoronary atherosclerosis. Selection criteria for monotherapy include LDL-cholesterol lowering efficacy, CHD morbidity/mortality and overall survival benefits, no adverse effect on concomitant metabolic diseases (e.g., diabetes), tolerability, long-term safety, simple dose schedule, and cost effectiveness. However, in refractory hypercholesterolemia combination therapy may be required. Secondary prevention and primary prevention in individuals at high CHD risk are cost effective.