Lipoprotein lipid and apo targets are determined according to available evidence from clinical trials and epidemiological studies (). Most studies have used the LDL-C level as a therapeutic goal, and targets are derived from these data. Secondary targets, including the TC/HDL-C ratio, non-HDL cholesterol and apo B levels (47
), are based on post hoc analyses. The TC/HDL-C ratio is the best discriminator between CAD cases and controls (48
), although some studies, such as the INTERHEART study (49
), suggest that the apo B/apo A1 ratio can be a useful alternative.
Risk categories and treatment recommendations
Several recent randomized controlled trials with clinical end points, including the TNT (2
), IDEAL (3
) and PROVE-IT (4
) studies, indicate that an LDL-C target of lower than 2.0 mmol/L is optimal for high-risk individuals with established CAD. This conclusion is further supported by two surrogate end point studies, REVERSal of Atherosclerosis with Lipitor (REVERSAL) (50
) and A Study To Evaluate the effect of Rosuvastatin On Intravascular ultrasound-Derived coronary atheroma burden (ASTEROID) (51
). The REVERSAL study demonstrated slowing or halting of the progression of atherosclerosis, whereas ASTEROID documented significant regression of coronary artery atherosclerosis by assessing atheroma volume using intravascular ultrasound methodology.
A major consideration in terms of pharmacological therapy for patients in the low- to intermediate-risk categories is cost (19
). However, analyses of cost efficacy in primary prevention have generally been based on data from early statin intervention studies (19
). In a recent meta-analysis of 14 randomized trials, the Cholesterol Treatment Trialists’ (CTT) Collaborators reported that each mmol/L reduction in LDL-C resulted in a 25% decrease in major coronary events, a 19% decrease in coronary mortality and a 12% reduction in all-cause mortality (54
). In contrast to the relatively moderate degree of cholesterol reduction achieved in the early statin trials, it is now generally feasible and common clinical practice to lower patient LDL-C levels by 2 mmol/L to 2.5 mmol/L with proportionately greater efficacy in reducing clinical events. As noted by Law et al (55
), after five years of continuous treatment, an LDL-C reduction of 1.8 mmol/L is estimated to reduce CAD events by 61%. Clearly, the number needed to treat, or cost efficacy, of statin therapy is contingent not only on the absolute level of risk, but on the LDL-C-lowering efficacy of the intervention chosen. Thus, for those individuals in the low- and intermediate-risk categories, who are candidates for statin therapy, treatment to lower LDL-C by at least 40% is generally appropriate.
- The primary target of therapy is the LDL-C level (class I, level A).
- The secondary target is the TC/HDL-C ratio (class IIa, level A).