Background: Drug treatment of hypercholesterolemia remains controversial. Central to the debate are the results of the major placebo-controlled clinical trials of pharmacologic treatment of hypercholesterolemia.
Methods: Conventions and principles of clinical epidemiology are used to review the four major clinical trials of drug treatment of hypercholesterolemia. The review translates the results of these large, epidemiologically oriented experiments into terms that are applicable to managing patients at the individual level.
Results: Clofibrate is an ineffective treatment. Primary prevention with gemfibrizol or cholestyramine requires treating approximately 50 middle-aged men for 10 years to avert one adverse outcome. Secondary prevention with niacin for men with a prior myocardial infarction requires treatment of 10 to 15 patients for 10 years to prevent one adverse outcome.
Conclusions: While drug treatment of hypercholesterolemia in middle-aged men can prevent death and morbidity, the magnitude of the effectiveness is modest. Because a critical factor influencing the magnitude of benefit is the underlying risk of adverse events in the population under treatment, physicians should target interventions to populations that may benefit the most. In populations for whom the magnitude of effectiveness is likely to be modest, physicians should exercise clinical judgment when deciding what degree of benefit justifies treatment in individual cases.