The British Journal of Diabetes & Vascular Disease

There are health inequalities in distribution of coronary heart disease (CHD). The National Service Framework (NSF) for CHD sets national clinical and organisational standards, defines service models, and establishes performance indicators. The four waves of the primary care collaborative have shown that, by offering structured and systematic care, secondary prevention can be improved. The basic remit of primary care trusts is to improve the health of their population, to provide access to appropriate services, and to integrate these services.

Randomised controlled trials uniformly show that lowering low-density lipoprotein (LDL) cholesterol results in a predictable and consistent reduction in coronary heart disease (CHD) events. The Heart Protection Study showed that the relative risk reduction in major vascular events was consistent irrespective of the LDL level at baseline. There appears to be no lower threshold level. Trials show that the greater the reduction in LDL, the greater the CHD risk reduction observed.

The management of dyslipidaemia is likely to follow the example of hypertension, such that the effective regulation of the lipid profile will be achieved by combination drug therapy.

The Joint British Societies guidelines on the prevention of coronary heart disease (CHD) are being revised. Target populations will be patients with any symptomatic presentation of atherosclerotic disease, whatever the vascular territory. The first-degree relatives of patients with premature cardiovascular disease also need to be targeted. Third, individuals at high multifactorial risk of developing cardiovascular disease need to be targeted.

New risk prediction charts are being produced. Patients with a cardiovascular risk of ≥ 20% over 10 years (equivalent to a CHD risk of 15% over 10 years) will require investigation and treatment to blood pressure and lipid targets. Those with a cardiovascular disease risk below this threshold require lifestyle advice.

There is a wide variation in plasma total cholesterol levels in populations that are genetically similar: these variations are driven by the environment. We absorb 40—50% of our cholesterol from the diet, and synthesise 50—60% in the liver. Cholesterol absorption inhibitors target the exogenous pathway of cholesterol absorption.

Agents that act on different pathways in cholesterol metabolism, such as statins and cholesterol absorption inhibitors, can be co-administered in an attempt to achieve complementary or synergistic effects on lipid control.

In animal models, ezetimibe has been observed to lower plasma total, chylomicron, very-low density lipoprotein (VLDL) and low-density lipoprotein (LDL) cholesterol levels.

It inhibits the development of atherosclerosis in ApoE knockout mice. In combination with statins in dogs, it reduces plasma cholesterol in a synergistic manner.

In a study in humans, treatment with ezetimibe gave a 54% reduction in absorption of cholesterol. There was a wide range of cholesterol absorption and drug activity among these individuals.

Statins cannot always bring plasma lipoprotein levels to target because they only attack one element of the cholesterol homoeostatic pathway. By inhibiting cholesterol absorption as well, using ezetimibe, additional benefits may be obtained. Ezetimibe co-administered with low-dose statin may give an additional 10% reduction in triglyceride, 14% reduction in low-density lipoprotein (LDL) cholesterol, and a 5% rise in high-density lipoprotein (HDL) cholesterol compared to statin alone.

In one study, significantly better National Cholesterol Education Program goal achievement was seen with co-administration of ezetimibe and a statin compared to statin treatment alone. Ezetimibe plus a statin is generally well tolerated.

The ENHANCE study will assess the effect of ezetimibe plus simvastatin in patients with heterozygous familial hypercholesterolaemia. Carotid artery intima-media thickness will be measured, which is able to predict a progression to cardiovascular or cerebrovascular events.

The SEAS study will evaluate whether treatment with ezetimibe and simvastatin, compared with placebo, will reduce the risk of major cardiovascular events in patients with aortic stenosis.

The SHARP study will measure major vascular events in patients with chronic kidney disease or who are receiving dialysis. Ezetimibe and simvastatin treatment will be compared with placebo.

By the year 2020, cardiovascular disease will be the world's biggest cause of premature death. As the plasma cholesterol is lowered, the incidence of coronary heart disease (CHD) events is reduced. European data on secondary prevention show that many patients have not had a plasma cholesterol recorded — even those with a diagnosis of CHD. English data show that only half of patients with a cholesterol measurement are being prescribed a statin, and only half of those are being treated to target. Poor public understanding of this subject area is one obstacle to progress.