Benefits and risks of HMG-CoA reductase inhibitors in the prevention of coronary heart disease: a reappraisal

Abstract

Although several cholesterol-lowering interventions have reduced coronary heart disease (CHD) events in clinical trials, drug therapy for hypercholesterolaemia has not been as widely used as the US and European guidelines recommend, mainly because until recently there was insufficient clinical trial evidence for improved survival. The Scandinavian Simvastatin Survival Study (4S) is the first trial of lipid-lowering therapy to demonstrate an unequivocal reduction in total mortality. Largely as a result of this study, there is now little disagreement on the necessity to reduce low density lipoprotein (LDL) cholesterol effectively in hypercholesterolaemic patients with CHD. Many physicians believe it is also important to reduce elevated levels of LDL cholesterol in patients without overt coronary disease, but more clinical trial evidence will be required before this is universally accepted. Inhibitors of HMG-CoA reductase are the most effective class of agents for this purpose, and have become widely used. It is likely that the magnitude of risk reduction produced by lipid-lowering therapy is proportional to the degree of cholesterol lowering achieved, which is an important consideration when selecting an agent and deciding the dosage to use. The results of several multicentre comparative trials have clearly established that the 4 members of the class are not all equipotent on a mg basis in terms of their effects on lowering LDL cholesterol. They have shown that the hypolipidaemic effect of simvastatin 5 mg approximately equals that of pravastatin 15 mg and lovastatin 15 mg and that of fluvastatin 40 mg, all given once daily. The tolerability profiles of HMG-CoA reductase inhibitors are excellent. Five-year data are available for simvastatin and lovastatin, and to date there is no good evidence for important differences in safety or tolerability among the class.