Optimal lipid modification: the rationale for combination therapy.
BACKGROUND
An emphasis on more aggressive lipid-lowering, particularly of low-density lipoprotein cholesterol, to improve patient outcomes has led to an increased use of combination lipid-lowering drugs. This strategy, while potentially beneficial, has triggered concerns regarding fears of adverse effects, harmful drug interactions, and patient nonadherence.


OBJECTIVE
To present key data regarding combination lipid-altering therapy including use, rationale, major trials, benefits, potential adverse effects, compliance issues, and limitations.


METHODS
Literature was obtained from MEDLINE (1966 - June 2005) and references from selected articles.


RESULTS
A substantial body of evidence from epidemiological data and clinical trials indicates that aggressive lipid modification, especially low-density lipoprotein reduction, is associated with reduced cardiovascular events. Numerous studies utilizing various combinations of cholesterol-lowering agents including statin/fibrate, statin/niacin, statin/bile acid resin, and statin/ezetimibe have demonstrated significant changes in the lipid profile with acceptable safety. Long-term trials of combination therapy evaluating clinical outcomes or surrogate markers of cardiovascular disease, while limited, are promising.


CONCLUSIONS
Combining lipid-altering agents results in additional improvements in lipoproteins and has the potential to further reduce cardiovascular events beyond that of monotherapy.
Backes
James M
JM
Department of Pharmacy Practice, Lipid, Atherosclerosis, Metabolic and LDL Apheresis Center, University of Kansas Medical Center, Kansas City, KS 66160-7231, USA. jbackes@kumc.edu
Gibson
Cheryl A
CA
Howard
Patricia A
PA
D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001384:Azetidines / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D008078:Cholesterol, LDL / Q000097:blood; D002986:Clinical Trials as Topic / Q000379:methods; D002995:Clofibric Acid / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D000069438:Ezetimibe; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D009525:Niacin / Q000627:therapeutic use; D010349:Patient Compliance; D018579:Patient Selection; D017410:Practice Guidelines as Topic; D012107:Research Design; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009525:Niacin; D002995:Clofibric Acid; D000069438:Ezetimibe