Ezetimibe plus simvastatin for the treatment of hypercholesterolemia.
BACKGROUND
Cardiovascular disease is a major cause of death, and hypercholesterolemia is a major risk factor. Statins, with simvastatin among the most widely used, have ample evidence demonstrating prevention of cardiovascular events and mortality. Ezetimibe is effective at improving serum lipids in combination with statins or alone, but its role has been controversial.


METHODS
Here, we provide an overview of the pharmacokinetics and pharmacodynamics of each component of the combination, as well as pharmacogenetic contributors. Regarding clinical efficacy, our focus will be on the post-marketing clinical trials of ezetimibe-simvastatin combination therapy. We broach the controversy around the role of ezetimibe, particularly in light of the results of the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT).


CONCLUSIONS
Ezetimibe in combination with simvastatin or other statins provides an excellent means of incremental lipid-lowering effect, although the clinical benefit has been uncertain. IMPROVE-IT is the first to demonstrate incremental cardiovascular risk reduction with the addition of ezetimibe to simvastatin. What the literature lacks is evidence around the common use of ezetimibe as monotherapy or add-on therapy to lower doses of statins in patients who fail to achieve adequate lipid lowering or do not tolerate high-dose statins.
London Health Sciences Centre-University Hospital , 339 Windermere Rd, London, Ontario N6A 5A5 , Canada +1 519 663 2922 ; +1 519 663 3217 ; sgryn@uwo.ca.
Steven E
SE
Gryn
Robert A
RA
Hegele
D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001384:Azetidines / Q000494:pharmacology / Q000627:therapeutic use*; D004338:Drug Combinations; D004357:Drug Synergism; D000069499:Ezetimibe, Simvastatin Drug Combination; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D010597:Pharmacogenetics; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*
D000924:Anticholesteremic Agents; D001384:Azetidines; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D019821:Simvastatin
drug combinations; ezetimibe; hydroxymethylglutaryl-CoA reductase inhibitors; hypercholesterolemia; simvastatin