This article is more than 5 years old. Information may no longer be current.
ENHANCE data: Ezetimibe did not reduce IMT for patients with genetic disorder
Ezetimibe/simvastatin combo did not affect intima-media thickness significantly more than simvastatin alone.
Click Here to Manage Email Alerts
Imaging results from the ENHANCE trial suggest that adding ezetimibe to simvastatin treatment may not affect intima-media thickness or cardiovascular events.
The ENHANCE trial, or Effect of Combination Ezetimibe and High-Dose Simvastatin Versus Simvastatin Alone on Patients with Heterozygous Familial Hypercholesterolemia, included 720 participants with heterozygous familial hypercholesterolemia.
Ezetimibe (Zetia, Schering-Plough, Merck) is often prescribed with simvastatin (Zocor, Schering-Plough, Merck), and study participants were assigned both medications in the form of ezetimibe-simvastatin pills (Vytorin, Schering-Plough, Merck).
Researchers assigned participants to ezetimibe/simvastatin 10/80 mg or 80 mg of simvastatin. The primary endpoint was mean change in intima-media thickness, which the researchers measured at three sites along the carotid arteries.
The change in mean intima-media thickness from baseline was 0.0111 mm in the ezetimibe/simvastatin group vs. 0.0058 mm in the simvastatin alone group (P=.29).
There was a 58% LDL cholesterol reduction after 24 months with the combination vs. a 41% reduction with simvastatin (P<.01).
Cardiovascular adverse events, including MI and non-fatal stroke, were slightly higher in the ezetimibe/simvastatin group, but these differences were not statistically significant. Although both drugs were well-tolerated and their safety profiles were similar, there was a statistically insignificant rise in mean intima-media thickness in the ezetimibe/simvastatin group compared with the simvastatin group.
In a press release, the American College of Cardiology cautioned patients not to panic and recommended that “major clinical decisions not be made on the basis of the ENHANCE study alone.
“Furthermore, the ACC notes that this trial is an imaging study and not a clinical-outcome study,” the ACC said in the release. “Final conclusions should not be made until the clinical outcome trials are presented. The ACC recommends that Zetia remain a reasonable option for patients who are currently on a high-dose statin but have not reached their lipid goals … [and] remains a reasonable option for patients who cannot tolerate statins or can only tolerate a low-dose statin.”
The companies have submitted an abstract of the full results to be presented next month in Chicago at the ACC Scientific Sessions. Currently, the pharmaceutical companies also are conducting three large outcome trials involving more than 20,000 high-risk patients. – by Christen Haigh and Eric Raible
This study gives me a bit of pause. The condition of heterozygous familial hypercholesterolemia is not necessarily the mechanism underlying the dyslipidemia in people with type 2 diabetes. Most importantly, the primary endpoint of carotid intima media thickness is not a clinical endpoint. It is a surrogate endpoint. The study was not powered to detect cardiovascular clinical event outcomes, and no difference was detected.
– Aaron M. Cypess, MD, PhD
Instructor, Harvard Medical School, Research
Associate and Staff Physician at Joslin Diabetes Center