NEW YORK, Dec 3 (Reuters) - Aggressive lowering of bad LDL cholesterol beyond current guidelines using Zetia with statins or statins alone led to reductions in atherosclerosis in patients with Type 2 diabetes, according to analysis of a study published in a medical journal.
The results should shed a more positive light on Zetia, the Merck & Co MRK.N and Schering-Plough Corp SGP.N drug that has faced criticism and sales declines after earlier studies.
Patients in the three-year study whose cholesterol was lowered only to current standard targets saw atherosclerosis increase, as measured by changes in thickness of the carotid artery, which can indicate increased heart attack risk.
The aggressive treatment group had their LDL cholesterol reduced to 70 or lower, while the standard group had LDL taken down to 100. The secondary analysis of data from the study called Sands was to appear in this week’s Journal of the American College of Cardiology (JACC).
While results with and without Zetia in the aggressive treatment group were considered to be similarly positive, many patients cannot get their bad cholesterol as low as 70 without the addition of Zetia, known chemically as ezetimibe.
In a similar five-year study of Type 2 diabetics in JACC, fenofibrate -- a member of a different class of drugs used mainly to lower blood fats called triglycerides -- failed to produce beneficial changes in carotid artery thickness. It also failed to reduce biomarkers of arterial inflammation.
Initial results of the Sands study, which compared aggressive lowering of cholesterol and blood pressure with standard lowering, were published in April. The secondary analysis looked at those who added Zetia to reach aggressive target levels and those who achieved the target using just potent statins, such as Pfizer Inc's PFE.N Lipitor.
“We think that these data suggest that ezetimibe is very reasonable to use as part of a strategy of reducing LDL cholesterol” in patients who cannot reach their target on statins alone “or who have some intolerance to statins,” Dr. Jerome Fleg, a researcher on the study and an author of the JACC article, said in an interview.
That should be a welcome message for Schering-Plough and Merck, the makers of Zetia and a related cholesterol drug Vytorin, both of which have experienced steep sales declines.
“The importance is getting down to the target and it doesn’t matter how you get there,” added Fleg, who suggested that an LDL target of 70 should be considered for patients at high risk of heart disease, such as diabetics.
Zetia and Vytorin have been bombarded by negative publicity in recent months as a pair of previous studies called Enhance and Seas left critics questioning the value and safety of Zetia. Vytorin combines Zetia, which cuts intestinal absorption of cholesterol, with Zocor, a widely used member of the statin class of drugs that are the world’s most prescribed medicines.
An editorial in JACC said the highly significant Sands results and the fenofibrate failure undercut Enhance study critics who asserted that fibrates rather than Zetia should first be used on top of statins.
Researchers said patients in the Sands study were also much more indicative of the typical high-risk population than those who participated in Enhance.
There were no serious adverse events related to the cholesterol drugs used in the Sands study, although researchers said the trial was not large enough to prove Zetia’s safety.
The Sands analysis involved 427 Native Americans with Type 2 diabetes aged 40 and over who had not had a previous heart attack or stroke. Native Americans are known to have high rates of diabetes.
After 36 months of therapy, changes in thickness of the carotid artery were measured to determine the effect, if any, on atherosclerosis -- the buildup of fatty plaque in the arteries that can lead to heart attacks and strokes.
In the aggressive treatment groups, carotid artery thickness decreased by 0.025 millimeter in the Zetia plus statin group and by 0.012 mm in the statin alone group -- considered to be statistically similar reductions.
Patients in the standard therapy group on average had an increase in artery thickness of 0.039 mm, an indication that atherosclerosis was progressing.
“While positive Sands data clearly will not offset the damage from Seas/Enhance, we see the (Zetia/Vytorin) franchise stabilizing,” JP Morgan analyst Chris Schott said in a note. (Additional reporting by Ransdell Pierson, editing by Matthew Lewis)
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