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May 18, 2011 — More than 42 million Americans suffer from high cholesterol, and 63 million more have borderline high cholesterol. Over time, high levels of LDL cholesterol – often called "bad cholesterol" – build up along the walls of arteries and blood vessels, which can lead to a high risk of heart disease, stroke and heart attack.
For some patients with high cholesterol, physicians routinely prescribe the combination of two cholesterol-lowering medications – statin therapy plus ezetimibe. A new study by University of Virginia Health System researchers, however, adds to mounting evidence that ezetimibe may not halt significant artery wall thickening, or atherosclerosis, in some patients. Despite the medication's proven effectiveness in lowering LDL cholesterol, U.Va. researchers found a notable progression of atherosclerosis in patients who added ezetimibe to their pre-existing cholesterol-lowering statin medication therapy.
The U.Va. study, now published online in the journal Atherosclerosis, follows two major clinical studies in 2008 and 2009 that also raised doubts about the benefits of ezetimibe in patients suffering from high LDL cholesterol levels, atherosclerosis and other heart-related problems.
"Patients in our study who had ezetimibe added to pre-existing statin therapy experienced on average a 22 percent decrease in their LDL cholesterol levels; however, we found that in these patients, atherosclerosis progressed at a rate of 4 percent per year over the two-year study period," said lead author Dr. Christopher M. Kramer, professor of radiology and medicine in the U.Va. School of Medicine and director of the U.Va. Cardiovascular Imaging Center. "That's a troubling rate of progression that occurred, despite the fall in cholesterol."
Kramer's study used magnetic resonance imaging to measure plaque buildup in the arteries of patients with peripheral arterial disease, who were treated with cholesterol-lowering medication for the two-year study period. Peripheral arterial disease is a circulatory problem in which narrowed arteries reduce blood flow to limbs, most commonly to the legs.
U.Va. researchers investigated two different study groups over the two-year trial period. One study group involved 34 peripheral arterial disease patients who had not previously been on any statin therapy. Statins are the most widely accepted and prescribed standard medication therapy for lowering cholesterol. This group was randomized to begin treatment with either simvastatin or simvastatin plus ezetimibe. In both of these patient subsets, atherosclerosis progression was halted.
The second study group involved 33 peripheral arterial disease patients who were already on statin therapy for at least one year and who had high LDL cholesterol levels. For this second study group, researchers added ezetimibe to patients' existing statin therapy. It was in this group that atherosclerosis progressed significantly.
Kramer's research team used magnetic resonance imaging to measure the volume of fatty buildup in lengths of 8 to 10 inches of the major leg artery wall. The same area was imaged at baseline and then yearly for two years.
"Because of the accuracy and reproducibility of these noninvasive MRI measurements," Kramer explains, "small changes can be measured over time in fewer patients than with some other imaging techniques."
Researchers have yet to understand why one class of cholesterol-lowering medications could result in different atherosclerosis outcomes over another class of drugs. The medications differ in the way they reduce cholesterol. Statins work by blocking a substance the liver needs to produce cholesterol, thereby causing a reduction in blood cholesterol levels. Ezetimibe works by reducing cholesterol through blocking the intestine's ability to absorb cholesterol during digestion.
Kramer's study was supported by grants from the National Heart, Lung and Blood Institute at the National Institutes of Health, the National Center for Research Resources, and the National Institute of Biomedical Imaging and Bioengineering.
Kramer's research group has completed a second study in the same patients with different endpoints, which will appear in an upcoming issue of the Journal of the American College of Cardiology.
Full text of the Atherosclerosis study can be found online on Science Direct.
May 18, 2011 — More than 42 million Americans suffer from high cholesterol, and 63 million more have borderline high cholesterol. Over time, high levels of LDL cholesterol – often called "bad cholesterol" – build up along the walls of arteries and blood vessels, which can lead to a high risk of heart disease, stroke and heart attack.
For some patients with high cholesterol, physicians routinely prescribe the combination of two cholesterol-lowering medications – statin therapy plus ezetimibe. A new study by University of Virginia Health System researchers, however, adds to mounting evidence that ezetimibe may not halt significant artery wall thickening, or atherosclerosis, in some patients. Despite the medication's proven effectiveness in lowering LDL cholesterol, U.Va. researchers found a notable progression of atherosclerosis in patients who added ezetimibe to their pre-existing cholesterol-lowering statin medication therapy.
The U.Va. study, now published online in the journal Atherosclerosis, follows two major clinical studies in 2008 and 2009 that also raised doubts about the benefits of ezetimibe in patients suffering from high LDL cholesterol levels, atherosclerosis and other heart-related problems.
"Patients in our study who had ezetimibe added to pre-existing statin therapy experienced on average a 22 percent decrease in their LDL cholesterol levels; however, we found that in these patients, atherosclerosis progressed at a rate of 4 percent per year over the two-year study period," said lead author Dr. Christopher M. Kramer, professor of radiology and medicine in the U.Va. School of Medicine and director of the U.Va. Cardiovascular Imaging Center. "That's a troubling rate of progression that occurred, despite the fall in cholesterol."
Kramer's study used magnetic resonance imaging to measure plaque buildup in the arteries of patients with peripheral arterial disease, who were treated with cholesterol-lowering medication for the two-year study period. Peripheral arterial disease is a circulatory problem in which narrowed arteries reduce blood flow to limbs, most commonly to the legs.
U.Va. researchers investigated two different study groups over the two-year trial period. One study group involved 34 peripheral arterial disease patients who had not previously been on any statin therapy. Statins are the most widely accepted and prescribed standard medication therapy for lowering cholesterol. This group was randomized to begin treatment with either simvastatin or simvastatin plus ezetimibe. In both of these patient subsets, atherosclerosis progression was halted.
The second study group involved 33 peripheral arterial disease patients who were already on statin therapy for at least one year and who had high LDL cholesterol levels. For this second study group, researchers added ezetimibe to patients' existing statin therapy. It was in this group that atherosclerosis progressed significantly.
Kramer's research team used magnetic resonance imaging to measure the volume of fatty buildup in lengths of 8 to 10 inches of the major leg artery wall. The same area was imaged at baseline and then yearly for two years.
"Because of the accuracy and reproducibility of these noninvasive MRI measurements," Kramer explains, "small changes can be measured over time in fewer patients than with some other imaging techniques."
Researchers have yet to understand why one class of cholesterol-lowering medications could result in different atherosclerosis outcomes over another class of drugs. The medications differ in the way they reduce cholesterol. Statins work by blocking a substance the liver needs to produce cholesterol, thereby causing a reduction in blood cholesterol levels. Ezetimibe works by reducing cholesterol through blocking the intestine's ability to absorb cholesterol during digestion.
Kramer's study was supported by grants from the National Heart, Lung and Blood Institute at the National Institutes of Health, the National Center for Research Resources, and the National Institute of Biomedical Imaging and Bioengineering.
Kramer's research group has completed a second study in the same patients with different endpoints, which will appear in an upcoming issue of the Journal of the American College of Cardiology.
Full text of the Atherosclerosis study can be found online on Science Direct.
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May 18, 2011
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