Context: Prior intravascular ultrasound(IVUS) trials have demonstrated slowing or halting of atherosclerosis progression with statin therapy but have not shown convincing evidence of regression using percent atheroma ...Context: Prior intravascular ultrasound(IVUS) trials have demonstrated slowing or halting of atherosclerosis progression with statin therapy but have not shown convincing evidence of regression using percent atheroma volume(PAV), the most rigorous IVUS measure of disease progression and regression. Objective: To assess whether very intensive statin therapy could regress coronary atherosclerosis as determined by IVUS imaging. Design and Setting: Prospective, open-label blinded endpoints trial(A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden[ASTEROID]) was performed at 53 community and tertiary care centers in the United States, Canada, Europe, and Australia. A motorized IVUS pullback was used to assess coronary atheroma burden at baseline and after 24 months of treatment. Each pair of baseline and follow-up IVUS assessments was analyzed in a blinded fashion. Patients: Between November 2002 and October 2003, 507 patients had a baseline IVUS examination and received at least 1 dose of study drug. After 24 months, 349 patients had evaluable serial IVUS examinations. Intervention: All patients received intensive statin therapy with rosuvastatin, 40 mg/d. Main Outcome Measures: Two primary efficacy parameters were prespecified: the change in PAV and the change in nominal atheroma volume in the 10-mm subsegment with the greatest disease severity at baseline. A secondary efficacy variable, change in normalized total atheroma volume for the entire artery, was also prespecified. Results: The mean(SD) baseline low-density lipoprotein cholesterol(LDL-C) level of 130.4(34.3) mg/dL declined to 60.8(20.0) mg/dL, a mean reduction of 53.2%(P< .001). Mean(SD) high-density lipoprotein cholesterol(HDL-C) level at baseline was 43.1(11.1) mg/dL, increasing to 49.0(12.6) mg/dL, an increase of 14.7%(P< .001). The mean(SD) change in PAV for the entire vessel was -0.98%(3.15%), with a median of-0.79%(97.5%CI,-1.21%to-0.53%)(P<.001 vs baseline). The mean(SD) change in atheroma volume in the most diseased 10-mm subsegment was-6.1(10.1) mm3, with a median of-5.6 mm3(97.5%CI,-6.8 to-4.0 mm3)(P< .001 vs baseline). Change in total atheroma volume showed a 6.8%median reduction; with a mean(SD) reduction of -14.7(25.7) mm3, with a median of-12.5 mm3(95%CI,-15.1 to-10.5 mm3)(P< .001 vs baseline). Adverse events were infrequent and similar to other statin trials. Conclusions: Very high-intensity statin therapy using rosuvastatin 40 mg/d achieved an average LDL-C of 60.8 mg/dL and increased HDL-C by 14.7%, resulting in significant regression of atherosclerosis for all 3 prespecified IVUS measures of disease burden. Treatment to LDL-C levels below currently accepted guidelines, when accompanied by significant HDL-C increases, can regress atherosclerosis in coronary disease patients. Further studies are needed to determine the effect of the observed changes on clinical outcome.展开更多
Background: Inhibiting the enzyme acyl-CoA:cholesterol acyltransferase(ACAT) has beneficial effects on foam cell formation and therefore has the potential to favorably influence the progression of coronary atheroscler...Background: Inhibiting the enzyme acyl-CoA:cholesterol acyltransferase(ACAT) has beneficial effects on foam cell formation and therefore has the potential to favorably influence the progression of coronary atherosclerosis. The aim of this study is to determine whether ACAT inhibition, when added to usual medical care, reduces atheroma progression in subjects with coronary artery disease. Methods: Five hundred thirty-four subjects with established coronary artery disease on angiography were randomized to receive the experimental ACAT inhibitor, pactimibe, 100 mg daily or matching placebo for 18 months. The primary efficacy parameter will be the nominal change in percent atheroma volume determined by analysis of pullback intravascular ultrasound(IVUS) images of matched coronary artery segments acquired at baseline and 18-month follow-up. In addition, the effect of pactimibe on plasma lipids and inflammatory markers and the incidence of clinical cardiovascular events will also be assessed. Conclusion: Serial IVUS has emerged as a sensitive imaging modality to assess the impact that novel antiatherosclerotic strategies have on the arterial wall. In this study, IVUS will be used to assess whether ACAT inhibition modifies progression of atherosclerotic plaque.展开更多
Aims: On the basis of the evidence from autopsy studies, it is accepted that compensatory enlargement(remodelling) of coronary arteries during progression of atherosclerosis diminishes once atheroma burden(cross-secti...Aims: On the basis of the evidence from autopsy studies, it is accepted that compensatory enlargement(remodelling) of coronary arteries during progression of atherosclerosis diminishes once atheroma burden(cross-sectional area stenosis) reaches ～40%. Our aim was to evaluate whether atheroma burden is a limiting factor for coronary arterial remodelling using in vivo serial intravascular ultrasound(IVUS). Methods and results: From the cohort of the Reversal of Atherosclerosis with Aggressive Lipid Lowering(REVERSAL) trial, we identified 210 focal coronary lesions at baseline IVUS. Of these, 128 lesions that had an increase in atheroma area at the 18-month follow-up IVUS were included in the analysis. Lesions were matched at baseline and follow-up. The increase in external elastic membrane(EEM) area for each mm2 increase in atheroma area was not significantly different in lesions with< 40 and ≥40%atheroma burden at baseline(1.62 vs. 1.28 mm2, P=0.30). There were no correlations between atheroma burden at baseline and change in EEM(r=0.02, P=0.86) or change in lumen(r=0.04, P=0.64) areas. Conclusion: Assessment of coronary arterial remodelling by serial IVUS revealed that compensatory remodelling is not limited by atheroma burden. Atheroma burden is not a determinant of arterial enlargement during the progression of atherosclerosis.展开更多
文摘Context: Prior intravascular ultrasound(IVUS) trials have demonstrated slowing or halting of atherosclerosis progression with statin therapy but have not shown convincing evidence of regression using percent atheroma volume(PAV), the most rigorous IVUS measure of disease progression and regression. Objective: To assess whether very intensive statin therapy could regress coronary atherosclerosis as determined by IVUS imaging. Design and Setting: Prospective, open-label blinded endpoints trial(A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden[ASTEROID]) was performed at 53 community and tertiary care centers in the United States, Canada, Europe, and Australia. A motorized IVUS pullback was used to assess coronary atheroma burden at baseline and after 24 months of treatment. Each pair of baseline and follow-up IVUS assessments was analyzed in a blinded fashion. Patients: Between November 2002 and October 2003, 507 patients had a baseline IVUS examination and received at least 1 dose of study drug. After 24 months, 349 patients had evaluable serial IVUS examinations. Intervention: All patients received intensive statin therapy with rosuvastatin, 40 mg/d. Main Outcome Measures: Two primary efficacy parameters were prespecified: the change in PAV and the change in nominal atheroma volume in the 10-mm subsegment with the greatest disease severity at baseline. A secondary efficacy variable, change in normalized total atheroma volume for the entire artery, was also prespecified. Results: The mean(SD) baseline low-density lipoprotein cholesterol(LDL-C) level of 130.4(34.3) mg/dL declined to 60.8(20.0) mg/dL, a mean reduction of 53.2%(P< .001). Mean(SD) high-density lipoprotein cholesterol(HDL-C) level at baseline was 43.1(11.1) mg/dL, increasing to 49.0(12.6) mg/dL, an increase of 14.7%(P< .001). The mean(SD) change in PAV for the entire vessel was -0.98%(3.15%), with a median of-0.79%(97.5%CI,-1.21%to-0.53%)(P<.001 vs baseline). The mean(SD) change in atheroma volume in the most diseased 10-mm subsegment was-6.1(10.1) mm3, with a median of-5.6 mm3(97.5%CI,-6.8 to-4.0 mm3)(P< .001 vs baseline). Change in total atheroma volume showed a 6.8%median reduction; with a mean(SD) reduction of -14.7(25.7) mm3, with a median of-12.5 mm3(95%CI,-15.1 to-10.5 mm3)(P< .001 vs baseline). Adverse events were infrequent and similar to other statin trials. Conclusions: Very high-intensity statin therapy using rosuvastatin 40 mg/d achieved an average LDL-C of 60.8 mg/dL and increased HDL-C by 14.7%, resulting in significant regression of atherosclerosis for all 3 prespecified IVUS measures of disease burden. Treatment to LDL-C levels below currently accepted guidelines, when accompanied by significant HDL-C increases, can regress atherosclerosis in coronary disease patients. Further studies are needed to determine the effect of the observed changes on clinical outcome.
文摘Background: Inhibiting the enzyme acyl-CoA:cholesterol acyltransferase(ACAT) has beneficial effects on foam cell formation and therefore has the potential to favorably influence the progression of coronary atherosclerosis. The aim of this study is to determine whether ACAT inhibition, when added to usual medical care, reduces atheroma progression in subjects with coronary artery disease. Methods: Five hundred thirty-four subjects with established coronary artery disease on angiography were randomized to receive the experimental ACAT inhibitor, pactimibe, 100 mg daily or matching placebo for 18 months. The primary efficacy parameter will be the nominal change in percent atheroma volume determined by analysis of pullback intravascular ultrasound(IVUS) images of matched coronary artery segments acquired at baseline and 18-month follow-up. In addition, the effect of pactimibe on plasma lipids and inflammatory markers and the incidence of clinical cardiovascular events will also be assessed. Conclusion: Serial IVUS has emerged as a sensitive imaging modality to assess the impact that novel antiatherosclerotic strategies have on the arterial wall. In this study, IVUS will be used to assess whether ACAT inhibition modifies progression of atherosclerotic plaque.
文摘Aims: On the basis of the evidence from autopsy studies, it is accepted that compensatory enlargement(remodelling) of coronary arteries during progression of atherosclerosis diminishes once atheroma burden(cross-sectional area stenosis) reaches ～40%. Our aim was to evaluate whether atheroma burden is a limiting factor for coronary arterial remodelling using in vivo serial intravascular ultrasound(IVUS). Methods and results: From the cohort of the Reversal of Atherosclerosis with Aggressive Lipid Lowering(REVERSAL) trial, we identified 210 focal coronary lesions at baseline IVUS. Of these, 128 lesions that had an increase in atheroma area at the 18-month follow-up IVUS were included in the analysis. Lesions were matched at baseline and follow-up. The increase in external elastic membrane(EEM) area for each mm2 increase in atheroma area was not significantly different in lesions with< 40 and ≥40%atheroma burden at baseline(1.62 vs. 1.28 mm2, P=0.30). There were no correlations between atheroma burden at baseline and change in EEM(r=0.02, P=0.86) or change in lumen(r=0.04, P=0.64) areas. Conclusion: Assessment of coronary arterial remodelling by serial IVUS revealed that compensatory remodelling is not limited by atheroma burden. Atheroma burden is not a determinant of arterial enlargement during the progression of atherosclerosis.
