Meta-analysis: The lower the LDL, the lower the risk of CHD
The ENHANCE study, a double-blind, randomized trial conducted over a period of 24 months, compared the effects of 80 mg per day of simvastatin with either placebo or 10 mg per day of ezetimibe in 720 patients with familial hypercholesterolemia. The primary outcome measure was a change in intimamedia thickness of the walls of the carotid and femoral arteries. The results of the study have raised the question of whether it is appropriate to target LDL cholesterol primarily to reduce CHD risk, because ezetimibe did not affect carotid artery intima-media thickness, despite its effectiveness in reducing LDL cholesterol.7
However, an earlier 19-trial metaregression analysis (81,859 patients with stable CHD) demonstrated that each 1% reduction in LDL cholesterol corresponded to a 1% decrease in risk for CHD. This result held true regardless of different approaches to treatment, which included diet, bile-acid sequestrant, statins, or ileal bypass surgery.8
Recommendations
The Adult Treatment Panel (ATP) III guidelines recommend an LDL level <100 mg/dL for high-risk patients (CHD or a CHD risk equivalent).9 An update to the ATP III guidelines states that the LDL goal of <100 mg/dL was as low as could be supported by clinical trial evidence at the time of publication and was also the practical limit of LDL reduction that could be achieved with standard treatment in most high-risk patients.1 The ATP III update offers the option of treating high-risk patients to a target LDL <70 mg/dL and clarifies that recent trials have shown no significant side effects associated with very low LDL levels.
Recent American Diabetes Association guidelines state that the LDL target should be <100 mg/dL in patients with diabetes, with the option of treating patients with both overt CHD and diabetes to an LDL of <70 mg/dL.10