Lack of therapeutic interchangeability of HMG-CoA reductase inhibitors

OBJECTIVE: To review relevant literature and provide an opinion on the class effect of hydroxymethylglutaryl coenzyme A reductase inhibitors (statins). DATA SOURCES: Primary and review articles were identified by MEDLINE search (1990-July 2002). STUDY SELECTION AND DATA EXTRACTION: Editorials, studies, and review articles related to the class effect or therapeutic interchangeability of statins were reviewed. Also included was information that is relevant to this topic. DATA SYNTHESIS: Although statins share common main actions, they may have clinically important differences in terms of efficacy and safety. At fixed or allowable dosages, rosuvastatin, atorvastatin, and simvastatin produced greater low-density lipoprotein cholesterol-lowering effects compared with other statins. Some statins have shown reduction in either cardiovascular and/or total mortality. Statins also differ in their structure, pharmacokinetics, potency, and rate of metabolism, any or all of which may have clinical significance. Although inconclusive, subtle differences in nonlipid effects of some statins may have contributed to positive benefits observed in clinical studies. As a result of drug-related deaths, cerivastatin was withdrawn voluntarily from the market, which may raise the question whether there is therapeutic interchangeability (due to class effect) among statins. CONCLUSIONS: Despite the competition for market share and strategies attempting to identify differences in therapeutic value, few head-to-head comparisons between statins have been performed. The limited, available data suggest that statins are not therapeutically interchangeable.