Effect of lipid-lowering therapies on C-reactive protein levels: a comprehensive meta-analysis of randomized controlled trials.

Chronic low degree inflammation is a hallmark of atherosclerotic cardiovascular disease. To assess the effect of lipid-lowering therapies (LLTs) on C-reactive protein (CRP), a biomarker of inflammation, we conducted a meta-analysis according to the PRISMA guidelines. Databases were searched from inception to July 2023. Inclusion criteria were: (1) randomized controlled trials (RCTs) in human, phase II, III or IV; (2) English language; (3) comparing the effect of lipid-lowering drugs vs placebo; (4) reporting the effects on CRP levels; (5) with intervention duration of more than 3 weeks; (6) and sample size (for both intervention and control group) over than 100 subjects. The between-group (treatment-placebo) CRP absolute mean differences and 95% confidence intervals (95%CI) were calculated for each drug class separately. A total of 171,668 subjects from 53 RCTs were included. CRP levels (mg/L) were significantly decreased by statins (-0.65 [-0.87 to -0.43], bempedoic acid (-0.43 [-0.67 to -0.20]), ezetimibe (-0.28 [-0.48 to -0.08]), and omega-3 fatty acids (omega3FAs, -0.27 [-0.52 to -0.01]). CRP was reduced by -0.40 (-1.17 to 0.38) with fibrates, although not statistically significant. A slight increase of CRP concentration was observed for PCSK9 inhibitors (0.11 [0.07 to 0.14]) and CETP inhibitors (0.10 [0.00 to 0.21]), the latter being not statistically significant. Meta-regression analysis did not show a significant correlation between changes in CRP and LDL-C or TG. Statins, bempedoic acid, ezetimibe, and omega3FAs significantly reduce serum CRP concentration, independently of LDL-C reductions. The impact of this anti-inflammatory effect in terms of cardiovascular prevention needs further investigation.