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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:3527-3533.)
© 1997 American Heart Association, Inc.

Articles

Cholesterol Reduction and Clinical Benefit

Are There Limits to Our Expectations?

Gunnar Fager; ; Olov Wiklund

From the Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden.

Correspondence to Gunnar Fager, MD, PhD, the Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden. E-mail Gunnar.Fager{at}Wlab.Wall.gu.se

Abstract Encouraging intervention trials drive our expectations toward more aggressive cholesterol-lowering therapies, lower target levels, and less severe hypercholesterolemia. Available studies may predict which patients, degrees of total cholesterol (TC) reduction, and baseline and target levels of TC provide the most clinical benefit. Data were pooled from seven primary and nine secondary controlled trials with major coronary heart disease (CHD) events as primary endpoints. The analysis showed that we can expect large reductions in CHD from TC reduction in primary and secondary prevention. However, the reduction is much larger in subjects with high TC and/or previous CHD events. The percent reduction in CHD increased exponentially with increasing percent TC reductions, which predicted >70% of the change in CHD. Consequently, we cannot expect cost-effective clinical benefits from mean reductions in TC >15 (LDL cholesterol >20)%. The TC level at the study endpoint correlated with CHD incidence irrespective of the study group and explained almost 45% of CHD incidence. The relationship was progressive and leveled off at a TC level below about 150 mg/dL (3.9 mmol/L) (LDL cholesterol 110 mg/dL [2.8 mmol/L]). Little extra clinical benefit can be expected from further reductions. We can expect an average 2% reduction in CHD events per percent reduction in TC. We can also expect a 2-fold greater clinical benefit among subjects with high initial TC levels than among those with low levels. Finally, we can expect that the cholesterol-attributable risk is reset to that predicted by the TC level achieved within 4 to 6 years.

Key Words: cholesterol • coronary heart disease • hypolipidemic drugs • hyperlipidemia • prevention

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