Merck/Schering-Plough Pharmaceuticals Provides Results of the ENHANCE Trial

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Merck/Schering-Plough Pharmaceuticals Provides Results of the ENHANCE Trial

http://www.docguide.com/news/content.nsf/news/852571020057CCF6852573D0005D5052

WHITEHOUSE STATION, NJ, KENILWORTH, NJ -- January 14, 2008 --

Merck/Schering-Plough Pharmaceuticals announced today the primary

endpoint and other results of the ENHANCE (Effect of Combination

Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone on the

Atherosclerotic Process in Patients with Heterozygous Familial

Hypercholesterolemia) trial. Merck/Schering-Plough has submitted an

abstract on the ENHANCE trial for presentation at the American College

of Cardiology meeting, which will be held in March 2008, and is awaiting

notification of acceptance from the College.

ENHANCE was a surrogate endpoint trial conducted in 720 patients

with Heterozygous Familial Hypercholesterolemia (HeFH), a rare condition

that affects approximately 0.2 percent of the population. All analyses

were conducted in accordance with the original statistical analysis

plan. The primary endpoint was the mean change in the intima-media

thickness (IMT) measured at three sites in the carotid arteries (the

right and left common carotid, internal carotid and carotid bulb)

between patients treated with ezetimibe/simvastatin 10/80 mg versus

patients treated with simvastatin 80 mg alone over a two year period.

There was no statistically significant difference between

treatment groups on the primary endpoint. The change from baseline in

the mean carotid IMT was 0.0111 mm for the ezetimibe/simvastatin 10/80

mg group versus 0.0058 mm for the simvastatin 80 mg group (P =0.29). At

baseline, the mean carotid IMT measurement for ezetimibe/simvastatin was

0.68 mm and for simvastatin 80 mg was 0.69 mm. There was also no

statistically significant difference between the treatment groups for

each of the components of the primary endpoint, including the common

carotid artery. Key secondary imaging endpoints showed no statistical

difference between treatment groups.

The overall incidence rates of treatment-related adverse events,

serious adverse events or adverse events leading to discontinuation were

generally similar between treatment groups. The incidence of consecutive

elevations of serum transaminases (≥ 3x ULN) was 10 out of 356 for

ezetimibe/simvastatin (2.8 percent) as compared to 8 out of 360 for

simvastatin (2.2 percent). Incidence of elevated creatine phosphokinase

(≥10xULN) was 4 out of 356 (1.1 percent) in the ezetimibe/simvastatin

group and 8 out of 360 (2.2 percent) in the simvastatin group and two

cases (0.6 percent) of CPK≥10xULN associated with muscle symptoms in the

ezetimibe/simvastatin group and one case (0.3 percent) in the

simvastatin group. There were no cases of rhabdomyolysis. Both medicines

were generally well tolerated.

Overall, the safety profiles of ezetimibe/simvastatin and

simvastatin alone were similar and generally consistent with their

product labels.

After washout, patients enrolled in the study had baseline LDL

cholesterol levels of 319 mg/dL in the group randomized to

ezetimibe/simvastatin and 318 mg/dL in the simvastatin group.

Approximately eighty percent of the patients enrolled in the ENHANCE

trial had previously been treated with statins.

In the trial, there was a significant difference in low-density

lipoprotein (LDL) cholesterol lowering seen between the treatment groups

-- 58 percent LDL cholesterol lowering at 24 months on

ezetimibe/simvastatin 10/80 mg as compared to 41 percent at 24 months on

simvastatin 80mg alone, (P<0.01).

The incidence rates of cardiovascular clinical events in ENHANCE

for the ezetimibe/simvastatin and simvastatin groups, respectively, were

as follows: cardiovascular death 2 out of 357 vs. 1 out of 363,

non-fatal myocardial infarction 3 out of 357 vs. 2 out of 363, non-fatal

stroke 1 out of 357 vs. 1 out of 363 and revascularization 6 out of 357

vs. 5 out of 363. There were no non-cardiovascular deaths or incidents

of resuscitated cardiac arrests in the ENHANCE trial. This surrogate

endpoint study was not powered nor designed to assess cardiovascular

clinical event outcomes.

Merck/Schering-Plough Pharmaceuticals is currently conducting

three large outcomes trials with ezetimibe/simvastatin, which involve

more than 20,000 high-risk patients, including the more than 10,000

patient IMPROVE-IT trial. No incremental benefit of

ezetimibe/simvastatin on cardiovascular morbidity and mortality over and

above that demonstrated for simvastatin has been established.

SOURCE: Merck & Co.

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