Randomized Evaluation of Atorvastatin in Patients With Coronary Heart Disease A Serial Intravascular Ultrasound Study

Abstract

oronary heart disease (CHD) is the leading cause of death in developed countries, and hypercholesterolemia is an independent risk factor for the progression of atheromatous plaque. Elevated serum cholesterol is causally associated with increased risk of CHD, and a series of randomized trials [1][2][3][4][5][6] have confirmed the benefits of HMG-CoA reductase inhibitors (statins) for hypercholesterolemia in the primary and secondary prevention of CHD. A recent meta-analysis showed that statin therapy reduced the risk of major coronary events by 31% and all-cause mortality by 21%. 7 Guidelines from medical organizations, such as the National Cholesterol Education Program Adult Treatment Panel and the Japan Atherosclerosis Society, suggest that serum low-density lipoproteincholesterol (LDL-C) should be maintained below 100 mg/dl in patients with CHD; 8,9 however, a recent survey, the Lipid Treatment Assessment Project, showed that only approximately 20% of high-risk patients currently achieve Circulation Journal Vol.71, December 2007 these goals. 10 Similar data illustrating the low proportion of patients who meet cholesterol goals have been reported in Europe 11 and Japan. 12 The incidence of CHD in the Japanese population is relatively lower than that reported in Western countries, and Japanese patients with CHD do not often have accompanying moderate or marked hypercholesterolemia. [13][14][15] Despite the rapid growth in knowledge of the clinical use of statins obtained from clinical trials, it is still unclear whether a marked reduction of LDL-C in patients with CHD and mild hypercholesterolemia would further reduce the clinical events. Subgroup analysis from the Cholesterol And Recurrent Event (CARE) trials 16 indicated no additional clinical benefit of treating LDL-C below 125 mg/dl, and the Pravastatin Pooling Project 17 results support this observation. Subgroup analysis from the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) study 18 showed no additional clinical benefit of intensive lipid-lowering therapy in patients with LDL-C levels below 125 mg/dl. By contrast, the Heart Prevention Study (HPS) indicated a clinical benefit of treating LDL-C from below 116 to below 77 mg/dl. 5 In parallel with clinical outcome trials, some trials using intravascular ultrasound (IVUS) have investigated the effects of statins on the progression of atherosclerosis. [19][20][21] The Reversal study showed a slowing of the progression of atherosclerosis during statin treatment, 20 and the ASTER-OID trial showed regression of coronary atherosclerosis if very low LDL-C levels were achieved. 21 In Japan, however, there have been few studies that show the effects of statin treatment on coronary atherosclerotic lesions. 22 Circ J 2007; 71: 1845 -1850 Background It is unclear whether a marked reduction of low-density lipoprotein-cholesterol (LDL-C) in patients with coronary heart disease (CHD) and mild hypercholesterolemia leads to less progression of atherosclerosis. Methods and ResultsPatients with...

Investigation of Blood Lipid Levels and Statin Interventions in Outpatients With Coronary Heart Disease in China The China Cholesterol Education Program (CCEP)

“…Therefore, statins should be prescribed for Chinese CHD patients, besides their benefit of lipid lowering. [26][27][28][29][30] In this study, 82.2% of the participants received statin therapy, which was higher than a result from Japan (36.3%) 31 and from Hong Kong where a report showed that only 37% of participants received lipid-lowering drugs. 32 It is also higher than the results of small trials in China and other reports.…”

Impact of Remnant Lipoprotein on Coronary Plaque Components

“…It is well known that low-density lipoprotein cholesterol (LDL-C) is a strong risk indicator for CVD, and the reduction of serum LDL-C levels with statins (3-hydroxy-3-methyl-glutaryl CoA reductase inhibitors) is a well-established treatment to reduce the CVD risks. The clinical usefulness of IVUS has been clearly proven by showing not only the regression in plaque volume but also the change of its composition during statin therapy [9][10][11] . Therefore, the reduction of serum LDL-C levels achieved by statins improves the clinical outcomes and modifies the histology of the plaque in the coronary arteries; however, many patients with well-controlled LDL-C levels achieved by statins still continue to experience cardiovascular events.…”

Carotid Magnetic Resonance Imaging

“…[55][56][57][58] Because of the comprehensive information provided by carotid MRI, this technique is also ideal for monitoring vessel wall changes under treatment. Carotid MRI has been extensively validated for its ability to monitor plaque regression.…”