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Statin Effects: Location May be Key
"Using MRI, we demonstrated intensive lipid-lowering by 20-milligram doses of atorvastatin, the maximal approved dose in Japan, with a marked LDL-cholesterol reduction of 47 percent and significant plaque regression in thoracic aorta. In abdominal aorta, however, even the 20-mg dose resulted in only a retardation of plaque progression, and a significant progression was observed in the 5-mg dose,” said Yukihiko Momiyama, M.D., at the National Defense Medical College in Saitama, Japan.
“Our results suggest that plaques in thoracic and abdominal aortas have different susceptibilities to lipid-lowering and that other factors, such as aging and hypertension, may be more important for plaque progression in abdominal aorta than in thoracic aorta,” Dr. Momiyama said.
The researchers, including lead author Atsushi Yonemura, M.D., used MRI scans to identify aortic plaques in 50 Japanese patients with high cholesterol levels, but few other major risk factors for coronary artery disease. The patients were randomly assigned to receive either daily doses of ether 20-milligrams or 5-milligrams of atorvastatin (brand name Lipitor®). A total of 40 patients completed at least one year of follow up, including 19 (7 men, 12 women) who received the 20-mg dose and 21 (7 men, 14 women) who were taking the 5-mg dose.
“Our study showed that intensive lipid-lowering by atorvastatin is more effective for aortic plaques, as well as for plaques in carotid and coronary arteries, than moderate lipid-lowering or conventional treatment, and that it is effective not only in Caucasians, but also in Japanese patients. However, we need to remember that the degree of lipid-lowering to regress plaques would be different among different vascular beds and that the dose of statin to induce intensive lipid-lowering would be different among different ethnicities,” Dr. Momiyama said.
He said that plaques in abdominal aorta tend to be more fibrous and not as closely linked to cholesterol levels.
Dr. Momiyama noted that this study looked only at changes in plaques as seen on MRI scans. It did not measure health outcomes, such as heart attacks. Interestingly, the study results also suggest there may be ethnic differences in responses to atorvastatin. The daily 20-mg dose used is the maximum allowed in Japan, while doctors in the United States and some other countries can prescribe atorvastatin doses of up to 80-mg per day.
“The 20-mg dose is much less than the 80-mg dose in trials in Western countries. However, the degree of LDL-cholesterol reduction by 20-mg in our study was similar to that by 80-mg in trials in Western countries. Japanese may be able to get a lot of benefits with the dose of statin much less than the dose used in Western countries,” Dr. Momiyama said.
Daisy Chien, Ph.D., at Cedars-Sinai Medical Center in Los Angeles, who was not connected with this study, said the interesting finding of different responses to statin treatment seen in plaques in the thoracic and abdominal segments of the aorta raises a number of questions.
“The question naturally is: why did the abdominal plaques behave differently from the thoracic plaques? Is this due to the nature of the plaque composition? Is this due to the size of the plaques? Are the abdominal plaques larger and harder to begin with and therefore show no regression? It will be interesting to see other groups validate this difference between the response of thoracic and abdominal plaque to drug treatment,” Dr. Chien said.
Source: American College of Cardiology