Pooled analysis demonstrates regression of coronary atherosclerosis with statins

Key Points

A post-hoc pooled analysis of data from 4 prospective, randomized trials evaluating the effect of statins on coronary atherosclerosis progression was recently published in the Journal of the American Medical Association (JAMA).

The objective of this analysis was to evaluate the effect of statin-related alterations in atherogenic lipoproteins on the rate of atheroma progression in patients with coronary artery disease (CAD). Patients included in the analysis had been treated with a statin in 1 of 4 intravascular ultrasound (IVUS) trials: the Reversal of Atherosclerosis With Aggressive Lipid Lowering (REVERSAL) trial, the Comparison of Amlodipine vs Enalapril to Limit Occurrence of Thrombosis (CAMELOT) trial, the ACAT Intravascular Atherosclerosis Treatment Evaluation (ACTIVATE) trial, and A Study to Evaluate the Effect of Rosuvastatin on Intravascular-Ultrasound Derived Indices of Coronary Atheroma Burden (ASTEROID).

Investigators who were blinded to treatment calculated the total atheroma volume (TAV) and percent atheroma volume (PAV) for patients in the 4 studies, using the same coronary artery segment and the same experimental protocol. Biochemical parameters, including low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), were recorded at baseline and after treatment.

With multivariate analysis, researchers demonstrated that baseline PAV, LDL-C level during treatment, change in HDL-C level, diabetes, hypertension, and age were all independent predictors of change in PAV. Similarly, baseline TAV, LDL-C level during treatment, change in HDL-C, body mass index, and age were independent predictors of change in TAV. The analysis also demonstrated that those patients with substantial atheroma regression (≥5%) had significantly lower cholesterol levels and LDL-C/HDL-C ratios and greater increases in HDL-C levels during treatment.

The authors stated: "The findings from this study provide evidence that increases in HDL-C in patients treated with statins are correlated with the beneficial effect of these agents on disease progression." They further suggested that "reduction of LDL-C to less than 87.5 mg/dL (2.3 mmol/L), when accompanied by an approximately 7.5% increase in HDL-C, is associated with coronary atherosclerosis regression."

Randomized, controlled trials have demonstrated reductions in cardiovascular events associated with statin-mediated reductions in LDL-C. Similarly, serial IVUS studies have suggested that very low LDL-C levels may induce coronary atherosclerosis regression. The authors stated that this study suggests that patients with established CAD should be treated to optimize levels of both HDL-C and LDL-C.

SOURCE Nicholls SJ, Tuzcu EM, Sipahi I, et al. Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. JAMA. 2007;297:499–508.