Heart Groups Call for Time Out In Ezetimibe/Simvastatin (Vytorin) Debate

By Peggy Peck
WASHINGTON, Jan. 16 -- Both the American College of Cardiology and the American Heart Association have warned against a rush to judgment on ezetimibe/simvastatin (Vytorin) on the basis of the scant details of the ENHANCE study released by the drug makers.
The ACC, amplifying the standard advice of "talk to your physician," urged patients not to panic.
The AHA said the study was neither large enough nor long enough to answer crucial clinical questions about the efficacy of the ezetimibe/simvastatin combination using the hard endpoint of myocardial infarction.
The primary endpoint of the ENHANCE trial was plaque burden measured by carotid artery intima-media thickness in a cohort of 720 patients with heterozygous familial hypercholesterolemia. There was no significant difference in intima-media thickness between the ezetimibe/simvastatin patients and those who received simvastatin alone.
In their statements, the two heart groups said that larger studies are under way and those studies are likely to provide more definitive data. AHA president Daniel W. Jones, M.D., of the University of Mississippi, said the only fair assessment of the drug must wait for results of those studies.
But Sidney Smith, M.D., of the University of North Carolina at Chapel Hill, pointed out what might be the 800-pound gorilla in the ezetimibe/simvastatin story -- that neither drug reduced LDLs to the recommended levels of less than 130 mg/dL for high-risk patients (or less than 100 mg/dL for patients with CVD).
In an interview, Dr. Smith agreed, however, that clinical decisions should await hard clinical data that are not yet available. Those data, he said, might suggest a benefit for ezetimibe/simvastatin when used in other populations that "are not as difficult as this group."
Neither the AHA, nor the ACC suggested a need for a moratorium on use of ezetimibe -- a suggestion made by Steven Nissen, M.D., of the Cleveland Clinic on Monday. Dr. Nissen is well known as an advocate for drug safety and a critic of drugs that carry cardiovascular risk.
Dr. Nissen was reacting to the sketchy results of the ENHANCE trial issued in a press release by Merck and Schering-Plough that confirmed null results for the primary endpoint. There was no significant difference in the mean change in carotid intima-media thickness between a change of 0.0111 mm for 356 ezetimibe/simvastatin patients versus 0.0058 mm for 360 controls (P=0.29) taking simvastatin alone.
The combination achieved a significantly greater decrease in LDLs, a 58% reduction in LDLs for the ezetimibe/simvastatin group versus 42% for simvastatin controls after 24 months (P<0.01). Full results of the trial are expected to be presented in late March at the ACC annual meeting and it is widely anticipated that the results will be simultaneously published in a peer-reviewed journal.
But in its statement, the ACC said its program committee had not yet selected abstracts for the late-breaking clinical trials session.
In related events, Rep. John Dingell (D-Mich.) said he was continuing to investigate why the ENHANCE trial data took so long to release. The trial was concluded almost two years ago and results have been expected for the past 18 months.