The recently issued guidance from the National Institute for Health and Clinical Excellence (NICE)1 on the cholesterol absorption inhibitor ezetimibe is welcome and summarised in this issue of Heart.2 NICE recommends its use in combination with a statin when more intensive low-density lipoprotein (LDL) lowering is indicated, and as monotherapy in the small proportion of patients who are intolerant of statin or in whom a statin is contraindicated. This endorsement comes at a time when the evidence is indicating that the lower the LDL cholesterol, the better.

Prospective observational studies show that, within the range of LDL cholesterol studied, lower levels are associated with lower coronary risk with no evidence of a threshold below which the risk is not reduced further.3 4 There is also now clear evidence that reducing LDL cholesterol by about 1.5 mmol/l is associated with a reduction in major cardiovascular events of about one-third,5 and more recent trial evidence suggests that larger reductions in LDL cholesterol are associated with larger reductions in vascular events.6 The Joint British Societies’ Guidelines on the prevention of cardiovascular disease in clinical practice (JBS 2) provide an overview of this evidence and recommend lipid-lowering therapy both for people with established cardiovascular disease and for those at more than 20% risk of developing it within the next 10 years.7

Given the available evidence, the key to achieving the most effective risk reductions is therefore to produce safely the largest possible LDL reductions. However, typically the guidelines translate this objective into target setting. Although the appropriateness of aiming for specific targets remains open to debate, JBS 2 sets optimal targets for total and LDL cholesterol of <4.0 mmol/l and <2.0 mmol/l, respectively, in high-risk patients. These current targets are substantially lower than the first joint British …