According to the recent meta-analyses published by the Cholesterol Treatment Trialists, there is a 23% reduction in major coronary events and a 21% reduction in major vascular events by a 1-mmol/L reduction in LDL-C, regardless the changes in other parameters, such as HDL-C or hs-CRP. Accordingly, the potency of statin in lowering LDL-C becomes the most important determinant of statin efficacy in reducing cardiovascular risks.

Epidemiology studies demonstrated a significant association between HDL level and risk of coronary heart disease. High HDL was associated with lower risk of coronary artery disease. Low level of HDL was suspected to be the major residual risk after statin therapy. However, the post-hoc analyses of major clinical trials of statins did not disclosed a significant role of HDL as a determinant of residual risk. The failure of AIM-HIGH trial further dispelled the role of HDL in reducing cardiovascular disease.

New HDL raising agents, such as CETP inhibitors, can significantly increase HDL level to more than 2 folds. Their effect in reducing cardiovascular disease is yet to be seen.