Lipids Online - Educational Resources in Atherosclerosis. Also covers coronary heart disease, hdl cholesterol, ldl cholesterol, free CME credit, continuing medical education, online CME course, medical CME conference
This is the first large randomized trial of two statin therapies using a new technology, intravascular ultrasound, and demonstrated that more intensive lipid-modifying therapy with atorvastatin 80 mg, which achieved a mean LDL-C of 79 mg/dL, stopped the progression of coronary atherosclerosis, whereas the pravastatin 40 mg group, with a mean LDL-C of 110 mg/dL, continued to have CAD progression. Although the absolute differences were small, endpoints were significantly different by predefined analysis after a treatment period of 18 months, which is a shorter duration than used in almost all QCA trials.
The major clinical implication of the study is that more intensive lipid-modifying therapy achieving an LDL-C level well below 100 mg/dL (on average, <80 mg/dL) was superior to less intensive therapy, i.e., "lower is better." In addition, this trial validates the use of intracoronary ultrasound to detect treatment effects on coronary atherosclerosis between two active therapies over a relatively short period of time. Additional research is needed to understand the relation between progression of CAD as detected by IVUS and development of clinical events.
Introduction
Although the clinical benefit of lipid-lowering statin therapy on progression of coronary artery disease (CAD) has been established in multiple placebo-controlled trials using quantitative coronary angiography (QCA), little information has been available on the comparative benefit of different treatment regimens on CAD progression. In the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial, the effects of intensive lipid lowering with atorvastatin 80 mg were compared with the effects of moderate lipid lowering with pravastatin 40 mg in 654 patients with angiographically demonstrated CAD and low-density lipoprotein cholesterol (LDL-C) between 125 mg/dL and 210 mg/dL. The primary endpoint was percent change in atheroma volume as assessed by intravascular ultrasound at 18-month follow-up.Key Points
LDL-C was reduced from a mean baseline of 150 mg/dL to 79 mg/dL with atorvastatin 80 mg/d (46% reduction) and 110 mg/dL with pravastatin 40 mg/d (25% reduction). The atorvastatin group also had significantly greater reductions in triglycerides (20% vs. 7% in the pravastatin group) and apolipoprotein (apo) B-100 (39% reduction vs. 22% in the pravastatin group); high-density lipoprotein cholesterol (HDL-C) was increased by 2.9% and 5.6% in the respective treatment groups, but the difference was not statistically significant. C-reactive protein (CRP) was reduced by 36% with atorvastatin 80 mg and 5% with pravastatin 40 mg. Analysis of the primary endpoint showed significantly less atherosclerotic progression with atorvastatin; progression did not occur in the atorvastatin group (–0.4% change in atheroma volume, p=.98), whereas progression was observed in the pravastatin group (2.7% increase in atheroma volume, p=.001). Significant benefit was also seen for secondary endpoints, including change in total atheroma volume and change in percent atheroma volume.Implications and Clinical Relevance
Previous randomized trials have used QCA to demonstrate that statin therapy significantly slowed the progression of atherosclerosis compared with placebo. These trials also showed that statin therapy increased the frequency of "regression" of lesions, as defined by increase in minimum lumen diameter or improvement in percent diameter stenosis. However, in previous trials using QCA, if one looks at the average change in all lesions with statin monotherapy, there was continued progression of atherosclerosis. Previous meta-analyses had suggested that LDL-C levels achieved may need to be far below 100 mg/dL to stop progression of CAD.This is the first large randomized trial of two statin therapies using a new technology, intravascular ultrasound, and demonstrated that more intensive lipid-modifying therapy with atorvastatin 80 mg, which achieved a mean LDL-C of 79 mg/dL, stopped the progression of coronary atherosclerosis, whereas the pravastatin 40 mg group, with a mean LDL-C of 110 mg/dL, continued to have CAD progression. Although the absolute differences were small, endpoints were significantly different by predefined analysis after a treatment period of 18 months, which is a shorter duration than used in almost all QCA trials.
The major clinical implication of the study is that more intensive lipid-modifying therapy achieving an LDL-C level well below 100 mg/dL (on average, <80 mg/dL) was superior to less intensive therapy, i.e., "lower is better." In addition, this trial validates the use of intracoronary ultrasound to detect treatment effects on coronary atherosclerosis between two active therapies over a relatively short period of time. Additional research is needed to understand the relation between progression of CAD as detected by IVUS and development of clinical events.