A new analysis of data from a recent study has found that the cholesterol-lowering drug ezetimibe (brand name Zetia) may have a role in protecting some people with Type 2 diabetes from developing cardiovascular disease.
The study, called the Stop Atherosclerosis in Native Diabetics Study (or SANDS), enrolled 427 Native Americans, age 40 and older, with Type 2 diabetes. The participants had no history of cardiovascular disease but did have atherosclerosis, or the build-up of fatty plaque in the arteries that is associated with cardiovascular disease. They were divided into two treatment groups: Members of the standard-treatment group aimed to lower their LDL (or “bad”) cholesterol levels to 100 mg/dl or less and lower their systolic blood pressure (the top number) to 130 mm Hg or less, while the those in the intensive-treatment group aimed for LDL cholesterol levels of 70 mg/dl or less and systolic blood pressure levels of 115 mm Hg or less.
The first cholesterol treatment used by the intensive group was statin drugs, but if these drugs alone did not lower LDL cholesterol enough, ezetimibe was added. Of the 223 people in the intensive-treatment group, 154 ended up taking statins alone and 69 took statins plus ezetimibe.
At both the beginning and the end of the three-year study period, participants had their carotid artery intima-media thickness (CIMT) measured by ultrasound. This test showed whether atherosclerosis was increasing or decreasing. It was found to have increased, or gotten worse, in the standard treatment group and decreased, or improved, to a similar extent in both arms of the intensive treatment group.
The researchers concluded that aggressively lowering LDL cholesterol levels with statins alone or with statins plus ezetimibe if needed appears to provide a similar benefit in protecting people with Type 2 diabetes from atherosclerosis. In other words, ezetimibe could play a role in reducing cardiovascular risk in people for whom statins alone do not lower cholesterol levels enough.
These findings contrast with the results of the ENHANCE trial, which I wrote about earlier this year in the blog entry “Vytorin Study Results Disappoint.” That study found that treatment with the statin drug simvastatin (Zocor) plus ezetimibe (sold together as the combination drug Vytorin) did not slow the growth of plaque in the carotid artery any more than treatment with simvastatin alone.
There are some important differences between the two studies. The ENHANCE study, with 720 participants, was larger than the SANDS study. It was also a double-blind study, meaning that participants and their doctors did not know which drugs they were taking, whereas SANDS was an open-label study. However, many participants in ENHANCE had taken cholesterol-lowering drugs before the start of the study, which may have influenced the study’s outcome, whereas SANDS participants had never before received treatment. Another difference was that SANDS focused on people with Type 2 diabetes, while ENHANCE did not.
The SANDS study results were published in the same issue of the Journal of the American College of Cardiology (JACC) that published the FIELD study of fenofibrate, which I wrote about last week (see “Fibrate Drug Alone Doesn’t Cut Heart Risks for Type 2’s”). Both of these studies used ultrasound to measure the progression of atherosclerosis.
Contrasting the SANDS study results with the ENHANCE results in an essay in the JACC, Evan A. Stein, MD, PhD, wrote that SANDS “restores the balance doctors and patients need to make a decision as to ezetimibe’s potential benefit.” He also pointed out that a much larger trial of ezetimibe, designed to measure the drug’s effect on risk of heart attacks, strokes, and cardiovascular death, is under way and should shed more light on the situation in a few years.