C‐reactive protein lowering with rosuvastatin in the METEOR study

Abstract

). C-reactive protein lowering with rosuvastatin in the METEOR study. J Intern Med 2010; 268: 155-161.Objectives. In addition to its LDL-C-lowering effects, statin treatment reduces the level of C-reactive protein (CRP). Long-term data on this effect in low-risk populations are limited. Furthermore, whether the CRP reduction is a consequence of LDL-C lowering or occurs independently remains unclear. We studied these aspects in the Measuring Effects on intima media Thickness: an Evaluation Of Rosuvastatin (METEOR) study, a randomized placebo-controlled trial amongst 984 low-risk subjects.Methods. METEOR is a randomized placebo-controlled trial that evaluated the effect of 40 mg of rosuvastatin on 2-year change in carotid intima media thickness (CIMT) amongst 984 low-risk patients (10-year Framingham risk <10%) with modest CIMT (CIMT ‡ 1.2 and <3.5 mm) and elevated LDL-C. CRP levels were measured at baseline and after 2 years of treatment.Results. Median baseline CRP was 1.4 mg L -1. Rosuvastatin lowered CRP significantly compared with placebo: )36% in the rosuvastatin group versus no change in the placebo group. There was no relation between change in CRP and change in LDL-C (Spearman correlation: 0.08; SE: 0.04). Stratified analyses showed that the CRP-lowering effect was present amongst all strata of baseline characteristics, including baseline lipids and CRP levels. However, the magnitude of CRP reduction was larger amongst women and participants older than 60 years.Conclusions. Rosuvastatin (40 mg) lowers CRP independently from its effects on LDL-C in low-risk subjects with normal baseline CRP levels and modest CIMT.

Reduction of C-reactive protein is not associated with reduced cardiovascular risk and mortality in patients treated with statins. A meta-analysis of 22 randomized trials

“…2E). Heterogeneity affecting MI analysis was resolved excluding trials with the most different effect sizes [28,30] and results were confirmed (RR: 0.894; CI: 0.847 to 0.945; p heterogeneity = 0.152; I 2 : 27.2%; p comparison b 0.001).…”

“…First, we could not find a significant correlation between LDL changes and CV events, that is apparently inconsistent with the well known relationship between these parameters observed from phase III intervention trials. The explanation most likely relies in the inclusion of trials [17,[19][20][21][23][24][25][26][27][28]32,33] that were not aimed to assess reduction of CV events but the changes of surrogate end-points induced by statins over short follow-up. Thus, we cannot exclude that longer duration of follow-up might change the strength of association.…”

“…Of those, 9 studies were excluded (i.e. trials not reporting CRP values or outcomes) and 22 trials [5,6,[14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] were finally included in the analysis, encompassing 54,213 patients, e.g. 27,556 assigned to active treatments and 26,657 to control groups (Fig.…”

“…Of 22 trials included in the study, 17 trials were analyzed for allcause death [5,6,14,15,[17][18][19][20][21][22][25][26][27][28][29]31,32], 15 for CV death [5,6,15,[17][18][19][20]22,[24][25][26][27]30,31,33], 15 for MI [5,6,15,16,18,[22][23][24][25][28][29][30][31][32][33], 13 for stroke [5,6,15,17,18,…”

“…Meta-analysis flow chart.primary prevention[6,16,20,23,28], no significant correlation between CRP changes and risk of MI (RC: − 0.031; CI: − 0.211 to 0.149; p heterogeneity = 0.145; I 2 : 44.3%; p comparison = 0.620), all-cause death (RC: −0.034; CI: −0.809 to 0.742; p heterogeneity = 0.773; I 2 : 0.0%; p regression = 0.680) and the composite outcome (RC: − 0.014; CI: − 0.131 to 0.103; p heterogeneity = 0.660; I 2 :…”