This analysis re-examines the therapeutic relationship between lower levels of harmful Low-density Lipoprotein (LDL) cholesterol and protection against cardiovascular disease outcomes. It concentrates on patients with LDL cholesterol levels that were already low, prior to the intensification of treatment and it includes the effects of statins, non-statins and even a drug designed to boost protective High-density Lipoprotein cholesterol (HDL). The study found that the relationship between the absolute size of the reduction in LDL cholesterol and the relative protection against cardiovascular disease was remarkably similar to that which was found in patients with average or elevated cholesterol levels. They also showed that very low cholesterol levels were safe within the periods that were studied.

Blood-pressure and blood glucose lowering treatments have limitations because overly aggressive therapy will cause symptoms such as fainting or loss of consciousness. This analysis is very important because it suggests that there is no such threshold for LDL cholesterol-lowering treatment. The greatest benefit from further reducing already low LDL cholesterol levels will be seen in patients with the highest risk of cardiovascular disease, including those with peripheral vascular disease and those in whom arteries continue to narrow despite usual therapy.

The accompanying editorial points out that the new information that has been included in the study warrants revision of the 2013 American guidelines on lipid management. This need is even more pressing in Australia where the guidelines are considerably older.