CHICAGO—The American College of Cardiology (ACC) acted swiftly to encourage its members to discontinue prescribing Vytorin to their patients after the results of the ENHANCE trial were officially delivered at the 2008 ACC Scientific Sessions on Sunday by lead author John J.P. Kastelein, MD, PhD, of the Academic Medical Center in Amsterdam, the Netherlands.
Data unveiled from the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial found that the reduction of LDL cholesterol by the addition of ezetimibe to simvastatin did not reduce intima–media thickness of the carotid artery wall in patients with familial hypercholesterolemia.
The combination of ezetimibe and simvastatin is marketed as Vytorin by its manufacturers, Merck and Schering-Plough.
"The study reinforces the need to adhere to current American College of Cardiology/American Heart Association Guidelines which recommend statins to the maximally tolerated dose or to goal as first line treatment for patients with coronary artery disease," ACC said in a statement this afternoon. "The data from the ENHANCE study should be considered as the NHLBI guidelines writing group is working on their update of the national cholesterol treatment guidelines in the coming months." The college continued to urge patients to speak with their physician before discontinuing any therapy.
“The predefined primary outcome was the change from baseline in ultrasonographic measurement of the mean carotid-artery intima–media thickness, which was defined as the average of the means of the far-wall intima–media thickness of the right and left common carotid arteries, carotid bulbs, and internal carotid arteries in the two study groups,” the authors wrote in the study published online before print in the New England Journal of Medicine.
“The key secondary outcomes were the proportion of patients with regression in the mean carotid-artery intima–media thickness from baseline, the proportion of patients with new carotid-artery plaques of more than 1.3 mm, the change from baseline in the mean maximal carotid-artery intima–media thickness (which was defined as the average of far wall maximum intima–media thickness of the right and left common carotid arteries, carotid bulbs, and internal carotid arteries), and the change from baseline in the average mean intima–media thickness of the carotid and common femoral arteries,” they wrote.
According to Kastelein, “We found no significant outcomes between either statins with or without ezetimibe at either endpoint.”
Although Vytorin did better job at lowering low-density lipoprotein (LDL) cholesterol than simvastatin alone, Kastelein noted that the Enhance study was only designed to answer the question of whether one drug that lowers cholesterol worked better than another in reducing intima-media arterial thickness.
“The reason for the failure to observe an incremental effect on intima–media thickness despite a reduction in levels of LDL cholesterol remains unknown,” Kastelein said.
A luminary panel comprised of Patrick T. O'Gara, MD, from Boston; Harlan M. Krumholz, MD, from New Haven, Conn.; Joseph V. Messer, MD, from Chicago; and Rick A. Nishimura, MD, from Rochester, Minn., offered their interpretation of the results at the meeting.
O’Gara said that the panel recommends that physicians first put patients on a high-dose statin, and then try other drugs before reaching for Vytorin.
“The strongest recommendation you could make on this panel is to turn back to statins,” Krumholz said of the ENHANCE results. “We spent a lot of money on this thing [in prescriptions written by U.S. physicians] and I think honestly we don't have any idea whether or not patients benefited.”