Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone on the Atherosclerotic Process in Patients With Heterozygous Familial Hypercholesterolemia (ENHANCE)
Trial Summary
Title:
Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone on the Atherosclerotic Process in Patients With Heterozygous Familial Hypercholesterolemia (ENHANCE)
Trial Sponsor: Merck/Schering-PloughYear
Presented: 2008
Description
The following information was derived from a Merck/Schering-Plough press release from January 14, 2008; full data are to be presented at the 2008 ACC Scientific Session.
Hypothesis
The goal of this trial was to compare the mean change in the intima-media thickness (IMT) measured at three sites in the carotid arteries between patients with Heterozygous Familial Hypercholesterolemia (HeFH) treated with ezetimibe/simvastatin 10/80 mg versus patients treated with high-dose simvastatin 80 mg alone over a two-year period.
Principal Findings
A total of 720 patients with HeFH were randomized in this multinational, randomized, double-blind, active comparator trial: 357 to the ezetimibe/simvastatin arm and 363 to the high-dose simvastatin arm. Images were obtained from the right and left carotid arteries at three sites at baseline, 6, 12, 18, and 24 months. The baseline low-density lipoprotein (LDL) cholesterol levels between the two arms were comparable (319 vs. 318 mg/dl; p=non-significant [NS]). Approximately 80% of patients enrolled in the trial had been on statins previously. The baseline mean carotid IMT measurements were similar between the two arms.
There was no statistically significant difference between the two arms with respect to the primary endpoint, the mean change in carotid IMT. The change from baseline for the ezetimibe/simvastatin arm was 0.0111 mm, compared with 0.0058 mm for the high-dose simvastatin arm (p=0.29).There was no difference in the incidence of cardiovascular clinical events: cardiovascular deaths (0.6 vs. 0.3%), non-fatal myocardial infarction (0.8% vs. 0.6%), non-fatal stroke (0.3% vs. 0.3%), and need for revascularization (1.7% vs. 1.4%) [p=NS for all].
There was, however, a significant reduction in LDL lowering noted in the ezetimibe/simvastatin arm compared with the simvastatin arm (58% vs. 41%; p<0.01).The overall incidence of treatment-related adverse events was similar between the two groups: consecutive elevations of serum transaminases ≥ 3X ULN (2.8% vs. 2.2%), elevated CPK ≥ 10 X ULN (1.1% vs. 2.2%), and elevated CPK ≥ 10X ULN with muscle symptoms (0.6% vs. 0.3%) [p=NS for all]. There were no cases of rhabdomyolysis reported in either arm.
Interpretation
The results of the multicenter, randomized ENHANCE trial seem to suggest that in patients with very high baseline LDL levels, such as those with heterozygous familial hypercholesterolemia, the combination of ezetimibe/simvastatin 10/80 mg does not result in significant changes in the mean carotid IMT at 2 years when compared with high-dose simvastatin 80 mg alone. There was also no difference in the incidence of cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, or need for revascularization, although this study was not powered to study clinical outcomes. The LDL-lowering effect of ezetimibe/simvastatin was greater than that achieved with high-dose simvastatin alone.
Although this was a negative study, it will be interesting to see if larger ongoing trials will be able to demonstrate any relative superiority of the combination of ezetimibe/simvastatin in improving cardiovascular outcomes in high-risk patients as compared with simvastatin alone.
Study DesignRandomized. Blinded. Parallel.
Patients Enrolled: 720
Mean Follow-Up: 24 months
Showing posts with label Sinvastatin. Show all posts
Showing posts with label Sinvastatin. Show all posts
Monday, January 14, 2008
Wednesday, December 12, 2007
Those Vytorin Results Will Be Right Out
Those Vytorin Results Will Be Right Out
Wall Street Journal
December 11, 2007, 9:26 pm
Usually, critics wait for a study’s results to come out before taking their shots. But in the case of a closely watched clinical test of Vytorin, a cholesterol pill marketed by Merck and Schering-Plough, the questions are already loud and pointed. They center on why the results of the study have remained a mystery for so long.
Although the study was finished in April 2006, doctors, patients and investors still don’t know how it turned out. Merck and Schering-Plough have been merrily marketing Vytorin as a potent reducer of cholesterol all along. Vytorin combines the drugs Zetia and Zocor in a single pill. But is the drug really better than plain old Zocor, now available as a cheap generic?
House Energy and Commerce Committee leaders John Dingell and Bart Stupak, both Michigan Democrats, ratcheted up the pressure on the companies today with a letter expressing their concern “with the delay…and the apparent manipulation of trial data.” (See the full text here.)
The trial at issue, called ENHANCE for short, looked at how well Vytorin slows the buildup of plaque in the arteries compared with a combination of Zocor and a placebo.
The companies said last month that the results would be presented at a meeting of the American College of Cardiology in March. But they also said then that the presentation would focus on an ultrasound measurement at only one point of the carotid artery. The study’s design called for the assessment of changes at three points of the artery as the primary endpoint. The apparent move of the carotid goal posts fueled questions about what the companies were up to.
Well, Team Vytorin has moved to placate questioning cardiologists by saying the main results will be revealed at the ACC meeting and that there will be no change in the endpoint after all.
“We have clarified today that we decided not to” change the endpoint, a Schering-Plough spokeswoman told the Health blog. The decision came after the companies got input from “leaders in the field in the U.S. and Europe,” she said. The spokeswoman said the company hasn’t formally received the letter from Congress, and she declined to comment on it.
A Merck spokesman said the company’s executives “just received and are reviewing the letter from the House Committee on Energy and Commerce and will respond in a timely manner.”
Wall Street Journal
December 11, 2007, 9:26 pm
Usually, critics wait for a study’s results to come out before taking their shots. But in the case of a closely watched clinical test of Vytorin, a cholesterol pill marketed by Merck and Schering-Plough, the questions are already loud and pointed. They center on why the results of the study have remained a mystery for so long.
Although the study was finished in April 2006, doctors, patients and investors still don’t know how it turned out. Merck and Schering-Plough have been merrily marketing Vytorin as a potent reducer of cholesterol all along. Vytorin combines the drugs Zetia and Zocor in a single pill. But is the drug really better than plain old Zocor, now available as a cheap generic?
House Energy and Commerce Committee leaders John Dingell and Bart Stupak, both Michigan Democrats, ratcheted up the pressure on the companies today with a letter expressing their concern “with the delay…and the apparent manipulation of trial data.” (See the full text here.)
The trial at issue, called ENHANCE for short, looked at how well Vytorin slows the buildup of plaque in the arteries compared with a combination of Zocor and a placebo.
The companies said last month that the results would be presented at a meeting of the American College of Cardiology in March. But they also said then that the presentation would focus on an ultrasound measurement at only one point of the carotid artery. The study’s design called for the assessment of changes at three points of the artery as the primary endpoint. The apparent move of the carotid goal posts fueled questions about what the companies were up to.
Well, Team Vytorin has moved to placate questioning cardiologists by saying the main results will be revealed at the ACC meeting and that there will be no change in the endpoint after all.
“We have clarified today that we decided not to” change the endpoint, a Schering-Plough spokeswoman told the Health blog. The decision came after the companies got input from “leaders in the field in the U.S. and Europe,” she said. The spokeswoman said the company hasn’t formally received the letter from Congress, and she declined to comment on it.
A Merck spokesman said the company’s executives “just received and are reviewing the letter from the House Committee on Energy and Commerce and will respond in a timely manner.”
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