Back in January, I wrote about the long-awaited results of the ENHANCE trial in which the two cholesterol-reducing drugs ezetimibe and simvastatin were pitted against just one, simvastatin, in terms of their ability to slow the progression of atherosclerosis, a gumming up of the arteries.
Even though the dual-therapy was more effective in reducing “bad cholesterol” (LDL cholesterol), it did nothing to improve the condition of the arteries. If anything, the progression of atherosclerosis worsened in those taking two medications rather than one (though this was not statistically significant). The fact that these results were disappointing, to say the least, might be why it took a couple of years for the manufacturers of ezetimibe and simvastatin to cough them up.
In the United States, the combination of ezetimibe and simvastatin is sold under the name of Vytorin. This product has been passed by the regulatory authorities there on the basis of its ability to reduce cholesterol levels. The assumption, of course, is that reduced cholesterol levels will translate into meaningful improvements in terms of things like heart attack rates (both fatal and non-fatal) and overall risk of death.
However, while the ENHANCE study did assess this specifically, the fact that Vytorin brought no improvements in the extent of atherosclerosis, as measured in the study, suggests that “clinical” endpoints, such as heart attack risk, might not have been improved either.
Last week saw the announcement of another study of Vytorin [1]. This four-year study assessed the effect of Vytorin (or placebo) in individuals suffering from a narrowing of the aortic valve in the heart (aortic stenosis). The valve is found at the junction of the heart and the main artery in the body—the aorta. The study is known as the SEAS (simvastatin and ezetimibe in aortic stenosis) study.
There was some good news from this study. The drug, compared to placebo, reduced the overall risk of “ischemic events,” such as non-fatal MI (myocardial infarction, also known as a heart attack), the need for bypass surgery, and the most common form of stroke.
However, Vytorin did not bring benefits (compared to placebo) in terms of events relating to problems with the aortic valve, valve-replacement surgery, hospitalization because of heart failure, and risk of death due to cardiovascular events (such as heart attacks and strokes). Overall, Vytorin was no better than placebo in reducing the main (primary) end points it was designed to assess, namely, aortic-valve and cardiovascular events.
Like the results of the ENHANCE trial, the results of the SEAS study can be described as disappointing. But the news gets worse when one considers that the group taking Vytorin were found to be at statistically, significantly increased risk of dying from cancer compared to the group taking the placebo.
Against this, though, two ongoing trials (known as SHARP and IMPROVE-IT) have failed to find such an association, apparently. However, cancer takes some time to develop and be significant enough to be diagnosed and cause death. While the SEAS trial lasted four years, the participants of the SHARP and IMPROVE-IT trials have typically been followed for one to two years, which may well not be long enough to properly assess the effect of Vytorin on cancer risk.
Reference:
[1] Vytorin misses primary end point in SEAS study, Clinical Cardiology, July 21, 2008
Dr. John Briffa is a London-based doctor and author with an interest in nutrition and natural medicine.
Dr. Briffa's Web site
