ABSTRACT
The Cholesterol and Recurrent Events (CARE) trial was a secondary prevention trial designed to test the effects of lowering cholesterol levels in patients with a history of myocardial infarction (MI) and average initial cholesterol levels.1 The direct association between serum cholesterol levels and coronary disease risk is well established. As serum cholesterol levels rise within a population, so too does the coronary disease risk. The highest risk is borne by those individuals with the highest cholesterol levels.2-5
The relationship between cholesterol levels and risk appears to be attenuated at lower levels of total cholesterol, such that the line describing this relationship is curvilinear rather that straight (Fig. 9.1).2-6
The landmark studies described in the preceding chapters have proven conclusively that lowering both serum total cholesterol and low-density lipoprotein (LDL) cholesterol with HMG-CoA reductase inhibitors in patients with hypercholesterolaemia reduces the rate of ischaemic cardiac events and reduces cardiac mortality.7,8 This is true whether cholesterol levels are reduced as a primary or as a secondary intervention strategy.7,8 It is important to remember, however, that an earlier meta-analysis by Holme9 found that the initial serum cholesterol level is an important determinant of the effects of cholesterol reduction. Higher cholesterol levels, particularly those greater than 7.1 mmol/l (275 mg/dl), predicted the patients who would benefit most from cholesterol lowering. The fact remains that the majority of patients with coronary heart disease (CHD), including those who have suffered an acute MI, do not have elevated levels of total or LDL cholesterol when compared with the general population.10,11 It was therefore not clear whether plasma cholesterol reduction would be of clinical benefit in patients with established CHD who have cholesterol levels of less than 6.2 mmol/l (240 mg/dl) and who have experienced less reduction in recurrent events than did sub-groups with elevated cholesterol levels (6.4-7.9 mmol/l; 247-305 mg/dl) in earlier trials.12-15
In most earlier clinical trials, both elderly patients and female patients were either excluded or relatively under-represented.16 From these trials it was not possible to draw conclusions about the effectiveness of cholesterol lowering in reducing the cardiovascular risk in either group, and particularly so for the majority of patients who have average cholesterol levels.
