To evaluate (1) the inter-individual variability of reductions in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) or apolipoprotein B (apoB) levels achieved with statin therapy, (2) the proportion of patients not reaching guideline-recommended lipid levels on high-dose statin therapy, and (3) the association between very low levels of atherogenic lipoproteins achieved with statin therapy and CVD risk.

Levels of atherogenic lipoproteins achieved with statin therapy are highly variable, but the consequence of this variability for cardiovascular disease (CVD) risk is not well documented.

Meta-analysis of individual patient data from 8 randomized controlled statin trials in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up.

Among 38,153 patients allocated to statin therapy, a total of 6,286 major cardiovascular events occurred in 5,387 study participants during follow-up. There was large inter-individual variability in the reductions of LDL-C, non-HDL-C and apoB achieved with a fixed statin dose. Over 40% of trial participants assigned to high-dose statin therapy did not reach an LDL-C target below 70 mg/dL. Compared to patients who achieved an LDL-C > 175 mg/dL, those who reached an LDL-C 75-100 mg/dL, 50-75 mg/dL and < 50 mg/dL had adjusted hazard ratios for major cardiovascular events of 0.56 (95%CI 0.46-0.67), 0.51 (95%CI 0.42-0,62) and 0.44 (95%CI 0.35-0.55), respectively. Similar associations were observed for non-HDL-C and apoB.

The reduction of LDL-C, non-HDL-C and apoB levels achieved with statin therapy displays large inter-individual variation. Among trial participants treated with high-dose statin therapy, over 40% do not reach an LDL-C target <70 mg/dL. Patients who achieve very low LDL-C levels have a lower risk of major cardiovascular events than those achieving moderately low levels.