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 sought to determine the earliest time point at which significant differences in atherosclerosis progression rates were detectable after initiation of statin therapy using data from the METEOR trial (Measuring Effects on intima media Thickness: an Evaluation Of Rosuvastatin).
Methods: METEOR was a double-blind, randomized, placebo-controlled trial among 984 low risk subjects, which studied the effect of LDL lowering with 40 mg rosuvastatin on the rate of change in carotid intima media thickness (CIMT) over time. Ultrasound assessments were made at 12 carotid artery sites at baseline and every 6 months up to two years. In these analyses, the data were cut at 6 months, 1 year, and 18 months, and compared with analysis of all data at 2 years, using the same statistical method.
Results: The difference in rate of maximum CIMT progression for all carotid artery sites (primary endpoint - near and far walls of the left and right common carotid artery [CCA], carotid bulb and internal carotid artery) between the rosuvastatin and placebo groups was apparent 6 months after baseline (0.0023 mm/yr and 0.0106 mm/yr, respectively p =0.36). After 12 months CIMT progression rates were significantly different between groups: 0.0032 mm/yr and 0.0133 mm/yr (p=0.049). This divergence grew with further follow-up: − 0.0009 mm/yr and 0.0131 mm/yr after 18 months (p<0.0001), and − 0.0014 mm/yr and 0.0131 mm/yr after 24 months of treatment (p<<178>0.0001). For the individual carotid artery segments, significant differences were seen at 12 months for the mean CIMT of the CCA, and at 18 months for the maximum CIMT of the bulb and the CCA.
Conclusion: Aggressive LDL lowering with rosuvastatin exerts its beneficial effect on atherosclerosis during the first year of treatment, which parallels the timing of event rate reduction seen in clinical trials. These findings suggest that, in trials examining the effects of treatment on CIMT progression, a duration of 12 months may be adequate, given sufficient sample size, high precision of measurements, and treatment effect.
Multilevel Models to Estimate Carotid Intima-Media Thickness Curves for Individual Cardiovascular Risk Evaluation
