Efficacy of Ezetimibe and Future Role in Managing High Risk Hyperlipidaemia
Efficacy of Ezetimibe and Future Role in Managing High Risk Hyperlipidaemia
A clinical audit of ezetimibe in the treatment of refractory hyperlipidaemia was conducted in 100 high-risk patients who failed to achieve desirable levels of total and low-density lipoprotein (LDL)-cholesterol on statins. Of these, 59 had familial hypercholesterolaemia (FH), the remainder had other aetiologies (non-FH). The percentage of patients achieving the total and LDL-cholesterol targets of the International Panel on the Management of FH or the Second Joint British Societies' guidelines in non-FH patients was determined.
Ezetimibe significantly decreased mean LDL-cholesterol when used as an adjunct to statins or as monotherapy, from 3.9 to 3.1 mmol/L in FH, from 3.4 to 2.4 mmol/L in non-FH and from 6.0 to 4.4 mmol/L in statin-intolerant patients. The decrease in LDL-cholesterol on statins was inversely correlated with the decrement after adding ezetimibe (r= -0.67, p<0.0001) but 15% of patients showed no further decrease. The percentage of patients achieving target levels of LDL-cholesterol was 27% on statins and 63% on statins plus ezetimibe (p<0.007). None of the non-FH patients achieved target levels on statins but 33% did so when ezetimibe was added (p<0.001).
Ezetimibe is an effective adjunct to statins for lowering LDL-cholesterol in refractory hyperlipidaemia, except in a minority of patients, and is a useful substitute in statin-intolerant subjects.
About 10 million deaths in the world are caused each year by coronary heart disease (CHD) and stroke. Comparative statistics in Britain are on a smaller scale but in relative terms, similar. Total mortality in the UK is approximately 600,000 annually, 36% of which is due to cardiovascular disease. Half of the latter is from CHD, a quarter from stroke and it is the main cause of premature mortality in both men and women. Recently it was estimated that the major modifiable risk factor, raised serum cholesterol, accounted for 45% of all myocardial infarcts in Western Europe.
The introduction of statins 20 years ago has revolutionised the management of hypercholesterolaemia and the prevention of cardiovascular disease. In the Cholesterol Treatment Trialists' Collaborators' meta-analysis the mean reduction in low-density lipoprotein (LDL)-cholesterol in subjects on statins was 29%, which was associated with a 21% decrease in coronary mortality. It was suggested that decreasing LDL-cholesterol by 50%, achievable with high doses of atorvastatin and rosuvastatin, could reduce the risk of coronary disease by 40% but this would still leave the majority of those on treatment vulnerable.
The recent introduction of the cholesterol absorption inhibitor, ezetimibe, offers an alternative to statin monotherapy. Combining ezetimibe with a statin augments the latter's LDL-lowering efficacy by an additional 15-20% and theoretically should achieve a reduction in CHD risk of similar magnitude, additional to that from statin alone. The effects of ezetimibe on cardiovascular disease remain to be determined but its use to treat hypercholesterolaemic patients who are intolerant of, or refractory to, statins has recently been endorsed by the National Institute for Health and Clinical Excellence (NICE). Here we describe a clinical audit of the role of ezetimibe in the management of such patients undergoing routine out-patient care in a hospital setting.
A clinical audit of ezetimibe in the treatment of refractory hyperlipidaemia was conducted in 100 high-risk patients who failed to achieve desirable levels of total and low-density lipoprotein (LDL)-cholesterol on statins. Of these, 59 had familial hypercholesterolaemia (FH), the remainder had other aetiologies (non-FH). The percentage of patients achieving the total and LDL-cholesterol targets of the International Panel on the Management of FH or the Second Joint British Societies' guidelines in non-FH patients was determined.
Ezetimibe significantly decreased mean LDL-cholesterol when used as an adjunct to statins or as monotherapy, from 3.9 to 3.1 mmol/L in FH, from 3.4 to 2.4 mmol/L in non-FH and from 6.0 to 4.4 mmol/L in statin-intolerant patients. The decrease in LDL-cholesterol on statins was inversely correlated with the decrement after adding ezetimibe (r= -0.67, p<0.0001) but 15% of patients showed no further decrease. The percentage of patients achieving target levels of LDL-cholesterol was 27% on statins and 63% on statins plus ezetimibe (p<0.007). None of the non-FH patients achieved target levels on statins but 33% did so when ezetimibe was added (p<0.001).
Ezetimibe is an effective adjunct to statins for lowering LDL-cholesterol in refractory hyperlipidaemia, except in a minority of patients, and is a useful substitute in statin-intolerant subjects.
About 10 million deaths in the world are caused each year by coronary heart disease (CHD) and stroke. Comparative statistics in Britain are on a smaller scale but in relative terms, similar. Total mortality in the UK is approximately 600,000 annually, 36% of which is due to cardiovascular disease. Half of the latter is from CHD, a quarter from stroke and it is the main cause of premature mortality in both men and women. Recently it was estimated that the major modifiable risk factor, raised serum cholesterol, accounted for 45% of all myocardial infarcts in Western Europe.
The introduction of statins 20 years ago has revolutionised the management of hypercholesterolaemia and the prevention of cardiovascular disease. In the Cholesterol Treatment Trialists' Collaborators' meta-analysis the mean reduction in low-density lipoprotein (LDL)-cholesterol in subjects on statins was 29%, which was associated with a 21% decrease in coronary mortality. It was suggested that decreasing LDL-cholesterol by 50%, achievable with high doses of atorvastatin and rosuvastatin, could reduce the risk of coronary disease by 40% but this would still leave the majority of those on treatment vulnerable.
The recent introduction of the cholesterol absorption inhibitor, ezetimibe, offers an alternative to statin monotherapy. Combining ezetimibe with a statin augments the latter's LDL-lowering efficacy by an additional 15-20% and theoretically should achieve a reduction in CHD risk of similar magnitude, additional to that from statin alone. The effects of ezetimibe on cardiovascular disease remain to be determined but its use to treat hypercholesterolaemic patients who are intolerant of, or refractory to, statins has recently been endorsed by the National Institute for Health and Clinical Excellence (NICE). Here we describe a clinical audit of the role of ezetimibe in the management of such patients undergoing routine out-patient care in a hospital setting.