HMG-CoA reductase inhibitors: a look back and a look ahead.

OBJECTIVES: This review is a follow-up to the Vancouver Symposium on hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors held in May 1990 (Can J Cardiol 1992;8 [Supplement A]: March 1992). The aim is to provide an update on the issues discussed at the time, focusing primarily on aspects of practical importance for the clinician and new developments. DATA SOURCES: The available literature on HMG-CoA reductase inhibitors from May 1990 to May 1991 was systematically reviewed. DATA SELECTION: The review focuses especially on human studies which provide a better understanding of mechanisms of action, pharmacokinetics, efficacy, safety and tolerance, as well as structure-function relationships.
CONCLUSIONS: A look back indicates that HMG-CoA reductase inhibitors, as a class, appear to be safe and effective for long term use and constitute a major drug addition for the control of hypercholesterolemia. Combination therapy may enhance effectiveness but close monitoring is needed when used in conjunction with fibrates and nicotinic acid because of potential muscle toxicity. A look ahead uncovers new properties that may be of potential benefit in the treatment of atherosclerosis, hypertension, cholelithiasis, mild renal disease and possibly thrombogenesis and cancer. In view of the fact that the magnitude of low density lipoprotein cholesterol lowering is commensurate with the degree of atherosclerosis regression, HMG-CoA reductase inhibitors provide a unique tool for the control of aggressive atherosclerotic vascular disease and for secondary prevention of coronary artery disease.