Ezetimibe plus simvastatin for the treatment of hypercholesterolemia


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.
Areas covered:

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).
Expert opinion:

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.

Steven E Gryn† & Robert A Hegele
†London Health Sciences Centre-University Hospital, London, Ontario, Canada

Expert Opin. Pharmacother. (2015) 16(8):1255-1262

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