This article is more than 5 years old. Information may no longer be current.
ENHANCE: Ezetimibe plus simvastatin not linked to increase in carotid intima-media thickness
Click Here to Manage Email Alerts
Ezetimibe plus simvastatin was not associated with increased carotid intima-media thickness, results from an FDA review suggested.
The FDA concluded its review of the final clinical report of the ENHANCE trial. The agency initially reported that the primary results of the ENHANCE trial raised questions about the relationship between carotid intima-media thickness and LDL levels in patients assigned ezetimibe plus simvastatin (Vytorin, Merck/Schering-Plough) vs. those assigned simvastatin alone (Zocor, Merck/Schering-Plough) or ezetimibe alone (Zetia, Merck/Schering-Plough).
According to the statement, carotid artery thickness did not significantly differ between patients in the ezetimibe plus simvastatin group vs. those assigned simvastatin alone. Patients assigned ezetimibe plus simvastatin had an average carotid artery thickness of 0.011 mm vs. 0.006 mm in the simvastatin alone group. LDL levels decreased by 56% in the ezetimibe plus simvastatin group compared with a 39% decrease in the simvastatin alone group.
“The results from ENHANCE do not change the FDA’s position that elevated LDL cholesterol is a risk factor for CVD and that lowering LDL cholesterol reduces the risk for CVD,” the agency wrote. “Based on available data, patients should not stop taking Vytorin or other cholesterol-lowering medications and should talk to their doctor if they have questions about Vytorin, Zetia or the ENHANCE trial.”
The IMPROVE-IT trial is underway to determine whether treatment with ezetimibe plus simvastatin reduces the risk for CV events compared with simvastatin alone. The study is expected to be completed in 2012. – by Eric Raible
The FDA’s statement contains no new clinically useful information. The results from the recent substudy of the SANDS trial in people with diabetes indicated that ezetimibe use to lower LDL further on top of a statin did indeed modestly lower carotid intima-media thickness. The final word on the clinical usefulness of ezetimibe will need to await the publication of the IMPROVE-IT results. For now, clinicians should focus on using a statin to get to their LDL and non-HDL targets. If a potent statin does not have the desired results, then the clinician has a variety of choices for a second-line lipid-lowering agent: niacin, fibrate, resin or ezetimibe. Niacin will be preferred when the HDL is low and a fibrate such as fenofibrate will be preferred when the triglyceride level is elevated. A resin or ezetimibe will be the likely choices when the only residual abnormality is elevated LDL.
– Roger S. Blumenthal, MD
Cardiology Today Section Editor
Numerous commentaries have been published summarizing the problems in study design and interpretation of the results and these are fairly and accurately reflected in the FDA statement. The most important issues with ENHANCE are the high rate of existing statin therapy and relatively low carotid intima-media thickness at entry combined with very high on-treatment LDL in both arms of the study. These levels are much higher than those shown to promote plaque regression in prior statin monotherapy trials.
– Steven R. Jones, MD
Assistant Professor of Medicine, Division of
Cardiology, Johns Hopkins Hospital, Baltimore