ARBITER: Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol

Abstract

Background-Whether marked LDL reduction to levels well below 100 mg/dL would further reduce the burden of cardiovascular disease is controversial. We compared the effects of 2 statins with widely differing potencies for LDL reduction (pravastatin 40 mg/d and atorvastatin 80 mg/d) on carotid intima-media thickness (CIMT). Methods and Results-This was a single-center, randomized, clinical trial of 161 patients (mean age, 60 years; 71.4% male; 46% with known cardiovascular disease) that met National Cholesterol Education Program (NCEP) II criteria for lipid-lowering therapy. The effects of atorvastatin (80 mg/d; nϭ79) and pravastatin (40 mg/d; nϭ82) on CIMT were compared using blinded, serial assessments of the far wall of the distal common carotid artery. Baseline CIMT and other characteristics were similar between study groups. As anticipated, atorvastatin was substantially more potent for LDL reduction after 12 months: in the atorvastatin group, LDL cholesterol was 76Ϯ23 mg/dL after 12 months (Ϫ48.5%); LDL cholesterol was 110Ϯ30 mg/dL in the pravastatin group (Ϫ27.2%; PϽ0.001). Atorvastatin induced progressive CIMT regression over 12 months (change in CIMT, Ϫ0.034Ϯ0.021 mm), whereas CIMT was stable in the pravastatin group (change of 0.025Ϯ 0.017 mm; Pϭ0.03). Conclusions-Marked LDL reduction (Ͻ100 mg/dL) with a high-potency statin provides superior efficacy for atherosclerosis regression at 1 year. This early effect on CIMT, a surrogate for clinical benefit, suggests that marked LDL reduction with synthetic statins may provide enhanced reduction in clinical coronary event rates. (Circulation.

High-Density Lipoprotein Cholesterol

“…45 Data from the Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER-2) study demonstrated that ER-niacin added to statin therapy may halt the progression of atherosclerosis, as measured by carotid intimamedia thickness among CHD patients with low HDL-C levels. 47 After 1 year of treatment, mean carotid intima-media thickness increased in the statin-only group but not in those treated with ER niacin. The addition of ER-niacin to background statin was well-tolerated with adherence exceeding 90%.…”

“…The addition of ER-niacin to background statin was well-tolerated with adherence exceeding 90%. 47 The National Institutes of Health (NIH) is sponsoring the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL Cholesterol/High Triglyceride and Impact on Global Health Outcomes (AIM-HIGH) trial which will evaluate the merits of simultaneously lowering LDL and raising HDL cholesterol levels, in patients randomized to ER-niacin plus simvastatin or to simvastatin alone. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial is testing fenofibrate plus a statin versus a statin alone in patients with type 2 diabetes.…”

Scheme for Combined Use of Statins and Ursodeoxycholic Acid in Patients With a High Risk of Cardiovascular Events and Concomitant Non-Alcoholic Fatty Liver Disease: Problems of Practical Application

“…Результат более чем впечатляющий, если учесть, что, например, в исследовании ARBITER применение атор-вастатина по 80 мг/сут приводило к двукратному сни-жению ХС ЛПНП, при этом средняя ТИМ каротидных ар-терий уменьшалась через 6 мес терапии на 0,016 мм, а через год -на 0,034 мм по отношению к исходным значениям [14]. Можно также вспомнить исследование ARBITER 2, в котором прием никотиновой кислоты по 1000 мг/сут приводил к приросту ХС ЛПВП на 21%, при этом через год терапии средняя ТИМ каротидных ар-терий оказалась только на 0,03 мм меньше, чем в груп-пе плацебо [15].…”

“…Можно также вспомнить исследование ARBITER 2, в котором прием никотиновой кислоты по 1000 мг/сут приводил к приросту ХС ЛПВП на 21%, при этом через год терапии средняя ТИМ каротидных ар-терий оказалась только на 0,03 мм меньше, чем в груп-пе плацебо [15]. Примечательно, что в обоих этих ис-следованиях оценка каротидных ультрасонограмм осу-ществлялась с использованием «слепого» метода [14,15], тогда как исследование B.D. Ozel Coskun и соавт.…”

Biomarkers in the Prevention and Treatment of Atherosclerosis: Need, Validation, and Future

“…Specifically, there have been three clinical trials in subjects with known CAD comparing the same therapies: pravastatin (40 mg/day) and atorvastatin (80 mg/day). Two of these studies used ultrasound to assess the progression of coronary atherosclerosis, one (ARBITER) with carotid ultrasound (Taylor et al, 2002) and one (REVERSAL) with coronary IVUS (Nissen et al, 2004). Both studies showed significant differences in the progression of atherosclerosis, favoring atorvastatin (80 mg/day).…”