Intensive lipid lowering may reduce progression of carotid atherosclerosis within 12 months of treatment: the METEOR study

Abstract

Background: In several statin trials, vascular event rates for treatment groups begin to separate 1 year after commencement of treatment. For atherosclerosis progression, the temporal sequence of the effect has not been defined. We used data from the Measuring Effects on intima media Thickness: an Evaluation Of Rosuvastatin (METEOR) trial to determine the earliest time point at which significant differences in atherosclerosis progression rates could be detected after initiation of statin therapy.

Methods: The METEOR trial was a double-blind, randomized placebo-controlled trial that studied the effect of LDL-C lowering with 40 mg rosuvastatin on the rate of change of carotid intima media thickness (CIMT) measured by B-mode ultrasound amongst 984 low risk subjects. Ultrasound assessments were made at baseline and every 6 months up to 2 years.

Results: Rosuvastatin treatment was associated with a 49% reduction in LDL-C-C, a 34% reduction in total cholesterol, an 8.0% increase in HDL-C and a 16% reduction in triglycerides (all P < 0.0001 compared with placebo). The difference in rate of mean maximum CIMT progression between the rosuvastatin and placebo groups (based on near and far wall measurements from both left and right common carotid and internal carotid segments and carotid bifurcation) was not statistically significant after 6 months (0.0023 mm year(-1) and 0.0106 mm year(-1), respectively P = 0.34). After 12 months, CIMT progression rates were significantly different between the groups: 0.0032 mm year(-1) and 0.0133 mm year(-1) in the rosuvastatin-treated and placebo-treated groups, respectively (P = 0.049). This divergence grew with further follow-up: -0.0009 mm year(-1) and 0.0131 mm year(-1) after 18 months (P < 0.001) and -0.0014 mm year(-1) and 0.0131 mm year(-1) after 24 months of treatment (P < 0.001). Results were stronger for the mean common CIMT progression (based on near and far wall measurements from both left and right common carotid segments).

Conclusion: Aggressive LDL-C lowering seems to exert its beneficial effect on atherosclerosis progression during the first 12 months of treatment. This parallels the timing of event reduction seen in clinical trials and suggests that the efficacy of lipid lowering treatment on CIMT progression can be evaluated in trials with a duration of 1 year, given sufficient sample size, high precision of measurements and a treatment effect comparable to that seen in METEOR.

Trial registration: ClinicalTrials.gov NCT00225589.