Rosuvastatin Slows Progression of Carotid Intima-Media Thickness: The METEOR-China Randomized Controlled Study

Abstract

Background: Atherosclerosis is the leading cause of cardiovascular disease worldwide, including in China. Primary prevention, through lipid-lowering, could avert development of atherosclerosis. Carotid intima-media thickness (CIMT) is a well-validated measure of atherosclerosis used in intervention studies as the primary outcome and alternative end point for cardiovascular disease events.

Methods: This randomized, double-blind, placebo-controlled, multicenter, parallel-group study assessed the effects of rosuvastatin 20 mg/d compared with placebo on progression of CIMT over 104 weeks in Chinese people with subclinical atherosclerosis. The primary end point was the annualized rate of change in mean of the maximum CIMT measurements taken 7× over the study period from each of 12 carotid artery sites (near and far walls of the right and left common carotid artery, carotid bulb, and internal carotid artery). Secondary end points included CIMT changes at different artery sites and lipid-parameter changes. Safety was also assessed.

Results: Participants were randomized (1:1) to receive rosuvastatin (n=272) or placebo (n=271). Baseline characteristics were well balanced between groups. The change in mean of the maximum CIMT of the 12 carotid sites was 0.0038 mm/y (95% CI, -0.0023-0.0100) for the rosuvastatin group versus 0.0142 mm/y (95% CI, 0.0080-0.0204) for the placebo group, with a difference of -0.0103 mm/y (95% CI, -0.0191 to -0.0016; P=0.020). For the CIMT secondary end points, the results were generally consistent with the primary end point. There were clinically relevant improvements in lipid parameters with rosuvastatin. We observed an adverse-event profile consistent with the known safety profile of rosuvastatin.

Conclusions: Rosuvastatin 20 mg/d significantly reduced the progression of CIMT over 2 years in Chinese adults with subclinical atherosclerosis and was well tolerated.

Registration: URL: https://www.

Clinicaltrials: gov; Unique identifier: NCT02546323.

Keywords: China; atherosclerosis; carotid intima-media thickness; dyslipidemia; primary prevention.

Figure 1.

Study flow chart. CIMT indicates carotid intima-media thickness. *Intima-media thickness (IMT) measurements at visit 2 (wk −4) and visit 3 (wk −2) were to meet inclusion criteria of maximum IMT ≥1.2 mm and <3.5 mm at any location in the carotid ultrasound scans. †Final IMT procedures were to be scheduled before discontinuation of study treatment. The second and final IMT procedure was to occur at or before visit 13 (wk 104), at the time of discontinuation of the study treatment. The 2 IMT procedures for visit 13 were to be performed on different days when possible.

Figure 2.

CONSORT participant flow diagram. The denominator for calculating all other percentages is the number of participants randomized in each treatment group and overall total. The intention-to-treat (ITT) population consisted of all randomized participants. The per-protocol (PP) analysis set is a subset of the ITT population that includes participants without any important protocol deviations that may affect the study outcome significantly or the interpretability of the study results. The safety analysis set consists of all participants who took at least one dose of the investigational product or placebo. n indicates number of participants. *Informed consent received. †The denominator for calculating percentage is the number of participants enrolled. ‡Includes participants withdrawn before receiving treatment.

Figure 3.

Difference between rosuvastatin and placebo in annualized rate of change and 95% CIs for the primary and secondary carotid intima-media thickness (CIMT) end points, mixed-effects model (intention-to-treat analysis set). Twelve carotid sites: near and far walls of the right and left common carotid artery (CCA), carotid bulb, and the internal carotid artery (ICA). MeanMax indicates mean of the maximum; and MeanMean, mean of the mean.

Figure 4.

Change from baseline in mean of the maximum (MeanMax) carotid intima-media thickness (CIMT) of the 12 carotid artery sites, by study visit ( intention-to-treat analysis set). Baseline is defined as the MeanMax CIMT of the 12 carotid artery sites averaged over wk −4 and wk −2. Wk 104 is defined as the MeanMax CIMT of the 12 carotid artery sites averaged over wk 104 (scan 1) and wk 104 (scan 2).