CHOLESTEROL REDUCTION AND CLINICAL BENEFIT - ARE THERE LIMITS TO OUR EXPECTATIONS

Encouraging intervention trials drive our expectations toward more agg ressive cholesterol-lowering therapies, lower target levels, and less severe hypercholesterolemia. Available studies may predict which patie nts, degrees of total cholesterol (TC) reduction, and baseline and tar get levels of TC provide the most clinical benefit. Data were pooled f rom seven primary and nine secondary controlled trials with major coro nary heart disease (CHD) events as primary endpoints. The analysis sho wed that we can expect large reductions in CHD from TC reduction in pr imary and secondary prevention. However, the reduction is much larger in subjects with high TC and/or previous CHD events. The percent reduc tion in CHD increased exponentially with increasing percent TC reducti ons, which predicted >70% of the change in CHD. Consequently, we canno t expect cost-effective clinical benefits from mean reductions in TC > 15 (LDL cholesterol >20)%. The TC level at the study endpoint correlat ed with CHD incidence irrespective of the study group and explained al most 45% of CHD incidence. The relationship was progressive and levele d off at a TC level below about 150 mg/dL (3.9 mmol/L) (LDL cholestero l approximate to 110 mg/dL [approximate to 2.8 mmol/L]). Little extra clinical benefit can be expected from further reductions. We can expec t an average 2% reduction in CHD events per percent reduction in TC. W e can also expect a 2-fold greater clinical benefit among subjects wit h high initial TC levels than among those with low levels. Finally, we can expect that the cholesterol-attributable risk is reset to that pr edicted by the TC level achieved within 4 to 6 years.