Support for Zetia protective CV effects ahead of IMPROVE-IT data
This article was originally published in Scrip
A nicely timed paper in this week's New England Journal of Medicine has given some theoretical support for the notion that reducing LDL-cholesterol levels using the cholesterol absorption inhibitor Zetia (Merck & Co's ezetimibe) may lead to a reduction in cardiovascular events.
Just days ahead of the presentation of the IMPROVE-IT study at the American Heart Association meeting in Chicago next week, researchers from the Myocardial Infarction Genetics Consortium say that patients with inactive genes for the protein inhibited by Zetia (Niemann–Pick C1-like 1 (NPC1L1)) have both reduced LDL cholesterol levels and a reduced risk of coronary heart disease. However, they caution: "Whether pharmacologic therapies that are focused on inhibiting NPC1L1 function reduce the risk of coronary heart disease remains to be determined."
Ezetimibe lowers plasma levels of LDL-cholesterol by inhibiting the activity of the NPC1L1 protein, but until IMPROVE-IT reports, it is still not known for sure whether such inhibition reduces the risk of cardiovascular events. Results of this trial have been keenly awaited since suspicions over the value of Zetia in addition to statin therapy were raised in 2008 by the ENHANCE study.
Human mutations that inactivate a gene encoding a drug target can mimic the action of an inhibitory drug and thus can be used to infer potential effects of that drug, and so the researchers funded by the US National Institutes of Health identified carriers of inactivating mutations and found the association with both plasma lipid levels and the risk of coronary heart disease.
"It's not possible to draw a direct conclusion about ezetimibe from this study," said first author Nathan Stitziel from the Washington University School of Medicine. "But we can say this genetic analysis gives us some confidence that targeting this gene should reduce the risk of heart attack. Whether ezetimibe specifically is the best way to target NPC1L1 remains an open question."