New analyses from a three-year study of adults with diabetes but without a history of cardiovascular disease suggest that those who need both ezetimibe and a statin to lower their cholesterol to target levels receive benefits similar to those who can achieve lower cholesterol targets with statins alone. The researchers report that ezetimibe appears to be an effective option for patients who are unable to achieve cholesterol goals with statins alone. This study demonstrates that the combination of ezetimibe plus a statin helped participants reach aggressive cholesterol targets and reduced carotid artery thickness, a sign that atherosclerosis (hardening of the arteries) was being reversed.
The new results also confirm the study's primary findings that aggressively lowering cholesterol and blood pressure levels below current targets in adults with type 2 diabetes may help to prevent – and possibly reverse – atherosclerosis, the leading cause of cardiovascular disease.
“Effect Of Statins Alone Versus Statins Plus Ezetimibe On Carotid Atherosclerosis In Type 2 Diabetes: The SANDS Trial,” is published in the Journal of the American College of Cardiology online December 3 and in the December 16/23 print version. The analyses were conducted by the Medstar Research Institute and supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health. Medications were donated by First Horizon Pharmacy, Merck and Co., and Pfizer, Inc.
SANDS (Stop Atherosclerosis in Native Diabetics Study) is the first clinical trial to compare two treatment targets for LDL (“bad”) cholesterol, non-HDL cholesterol, and systolic blood pressure (SBP) levels, key risk factors for cardiovascular disease, in adults with diabetes. Researchers followed nearly 500 American Indians ages 40 years and older (average age of 56) who had diabetes, elevated LDL cholesterol, and high SBP but no history of heart attack or stroke. Participants were randomly selected to be in one of two treatment groups. In the standard treatment group (about one-half of those enrolled), participants aimed to lower their LDL and non-HDL cholesterol and their blood pressure to standard targets (LDL cholesterol of 100mg/dL, non-HDL cholesterol of 130mg/dL, and SBP of 130mmHg). The second group sought more aggressive targets than are currently recommended (LDL cholesterol of 70mg/dL, non-HDL cholesterol of 100mg/dL, and SBP of 115mmHg).
To measure the effects of the two treatment groups on atherosclerosis, researchers measured the thickness of the walls of the blood vessels in the neck (carotid arteries) using ultrasound. In the April 9, 2008, issue of the Journal of the American Medical Association, they reported that at the end of the three-year study, the carotid artery thickness regressed on average in the aggressive treatment group, suggesting a partial reversal of atherosclerosis; in contrast, carotid artery thickness increased on average in the standard treatment group. Further analyses revealed that the decrease in carotid thickness was related to the decrease in LDL and non-HDL cholesterol levels but not to the decline in SBP.
In today's report, researchers looked at whether there were any differences between participants in the aggressive treatment group who lowered their cholesterol levels with statins alone compared to those who needed ezetimibe plus statins to reach their cholesterol targets; they also compared these two subgroups with participants in the standard group. This secondary analysis showed that both aggressive treatment subgroups achieved the same improvements in carotid artery thickness compared to the standard group, with no significant differences in adverse side effects.
Jerome L. Fleg, M.D., lead author and NHLBI project officer of SANDS, and Wm. James Howard, M.D., senior author, are available to comment on these findings. Howard is a principal investigator of the study and is vice president of academic affairs for Washington Hospital Center in Washington, D.C., part of Medstar.
Cardiovascular disease is the leading killer of people with diabetes, who are two to four times more likely to die from cardiovascular disease than those without diabetes. An estimated 21 million Americans have diabetes, and this number is expected to increase sharply in coming decades.
Statins are the most commonly used medication for lowering blood cholesterol levels. They work by interfering with the formation of cholesterol in the body. Ezetimibe, one of the newest FDA-approved cholesterol-lowering drugs, works by reducing the absorption of cholesterol from the intestine. Ezetimibe is typically used with a statin to lower blood cholesterol levels in patients who do not tolerate statins well or who are unable to reach LDL cholesterol targets with statins alone; the drug is also used alone (without statins) by some patients.
Other studies have shown that adding ezetimibe to a statin further reduces blood cholesterol levels; however, the drug's effect on clinical outcomes, such as heart attacks, stroke, and cardiovascular death, are unknown. Although SANDS was not large enough to determine the effect of ezetimibe on clinical outcomes, today's results suggest a potential role of ezetimibe combined with statins to lower the risk of cardiovascular disease in adults with diabetes.
To schedule an interview with Dr. Fleg, please contact the NHLBI Communications Office at 301-496-4236. Dr. Howard can be reached at 202-257-8170.
For more information:
• NHLBI news release, "Aggressively Lowering Cholesterol and Blood Pressure May Reverse Atherosclerosis in Adults with Diabetes," http://public.nhlbi.nih.gov/newsroom/home/GetPressRelease.aspx?id=2565
• FDA Consumer Update, "Making Sense of Vytorin Concerns," http://www.fda.gov/consumer/updates/vytorin071808.html
• Your Guide to Living Well With Heart Disease, http://www.nhlbi.nih.gov/health/public/heart/other/your_guide/living_well.htm
• Atherosclerosis, http://www.nhlbi.nih.gov/health/dci/Diseases/Atherosclerosis/Atherosclerosis_WhatIs.html
• National Diabetes Information Clearinghouse, http://diabetes.niddk.nih.gov/
• National Diabetes Education Program http://ndep.nih.gov/
Part of the National Institutes of Health, the National Heart, Lung, and Blood Institute plans, conducts, and supports research related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The Institute also administers national health education campaigns on women and heart disease, healthy weight for children, and other topics. NHLBI press releases and other materials are available online at www.nhlbi.nih.gov.
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