Treatment of mixed hyperlipidaemia using a combination of omega-3 fatty acids and HMG CoA reductase inhibitor

Abstract

Serum triglycerides tend to be particularly strong predictors of coronary risk. A meta-analysis of 17 population-based prospective studies indicates that after adjustment for high-density lipoprotein (HDL) cholesterol, a 1 mmol. l-1 increase in serum triglyceride level was associated with a 4% increase in risk in men and 37% in women. There is also evidence to indicate that serum triglyceride levels greater than 1-5 mmol . l-1 are associated with the presence of the more atherogenic small and dense low-density lipoprotein (LDL) subfraction. Many patients who develop coronary heart disease (CHD) have both hypercholesterolaemia and hypertriglyceridaemia. When diet is improved hypertrigly-ceridaemia up to 4 mmol . l-1 is often corrected, so that many of these patients can be managed on a statin alone. In some patients, however, and particularly those with genetic disorders such as familial combined hyperlipidaemia and the rarer remnant hyperlipidaemia (type III hyperlipoproteinaemia), the hyperlipidaemia responds poorly to lifestyle changes. In many patients with mixed hyperlipidaemia lipid-lowering monotherapy often produces improvement in serum cholesterol level, but not in serum triglyceride level or vice versa. One strategy is to use a combination of a statin and a fibrate in high-risk patients with mixed hyperlipidaemia. While effective, this combination increases the possibility of abnormal biochemical liver function tests and myalgia. Concentrated omega-3 fatty acids can lower serum triglyceride levels by up to 38% in a dose-dependent manner. Serum cholesterol levels usually remain unchanged, but there is a modest increase of about 6% in HDL cholesterol. We carried out a randomized double-blind, placebo-controlled trial using a parallel group design to examine the triglyceride-lowering effects of Omacor® in patients with established CHD and type lib hyperlipidaemia who were already on simvastatin. Our results show that, in patients with CHD and moderate hypertriglyceridaemia who were receiving simvastatin in a dose similar to that seen in the Scandinavian Simvastatin Survival Study, concentrated omega-3 fatty acids administration was effective in lowering serum triglyceride levels. Further long-term studies are needed to see if effective triglyceride level lowering using this combination will result in a decrease in new CHD events including non-fatal myocardial infarction over and above of that seen with statin use alone. © 2001 The European Society of Cardiology.