Head-to-head randomized trials of atorvastatin and rosuvastatin: a systematic review and meta-analysis of changes in inflammatory biomarkers
A Omayer, M I Mohamed, M Shahid, S M H Hoque, N E Mustafa, E Elsayed, T Shahid, M U Soomro, R AliAbstract
Background
Inflammation is a key driver in the development of cardiovascular disease, and statins have anti-inflammatory benefits that extend beyond lowering cholesterol. Although both atorvastatin and rosuvastatin have been shown to reduce inflammatory markers, studies directly comparing their anti-inflammatory effects have produced mixed and inconsistent results.
Purpose
This study aims to comprehensively compare the effects of atorvastatin and rosuvastatin on key inflammatory biomarkers across various clinical subgroups, follow-up durations, and dosages, optimizing treatment strategies based on individual patient characteristics.
Methods
PubMed, Web of Science, Scopus, and Cochrane were searched on August 14, 2024. Only randomized controlled trials were included. R software, version 4.4.1, was used for the analysis.
Results
Thirty-five head-to-head randomized trials (n = 6,148) were pooled to compare changes in C-reative protein (CRP), interleukin-6 (IL-6), adiponectin, and tumor necrosis factor-α (TNF-α). In the primary analysis, there was no significant difference in CRP reduction between atorvastatin and rosuvastatin (MD −0.53 mg/L; 95% CI −1.10 to 0.05; p = 0.07), although substantial heterogeneity (I² = 82%) limited confidence in the pooled estimate. After excluding one outlying study, heterogeneity decreased (I² = 63%) and rosuvastatin demonstrated a greater CRP reduction (MD −0.16 mg/L; 95% CI −0.28 to −0.03; p = 0.01); results were consistent when standardized effects were used (SMD −0.17; 95% CI −0.31 to −0.04; p = 0.01). A sensitivity analysis restricted to low risk-of-bias trials (n = 9) showed a smaller but still significant benefit favoring rosuvastatin (MD −0.08 mg/L; 95% CI −0.16 to −0.01; p = 0.03). Subgroup analyses by disease condition, follow-up duration, and dose suggested greater CRP lowering with rosuvastatin in diabetes and dyslipidemia, particularly at 6 weeks and at an 80/40 mg (atorvastatin/rosuvastatin) regimen (p ≤ 0.01). For non-CRP biomarkers, no overall between-group differences were observed for IL-6 (n = 484; MD −0.82; 95% CI −3.02 to 1.38; p = 0.46), adiponectin (n = 257; MD −1.78; 95% CI −4.70 to 1.14; p = 0.23), or TNF-α (n = 309; MD 0.23; 95% CI −0.05 to 0.52; p = 0.11). Meta-regression indicated that higher baseline CRP, higher HDL, and a greater prevalence of hypertension were associated with larger CRP reductions. Egger’s test did not suggest publication bias, and RoB 2 ratings were high risk 5.7% (2/35), some concerns 68.6% (24/35), and low risk 25.7% (9/35).
Conclusions
In head-to-head RCTs, rosuvastatin produced a modest but significantly greater CRP reduction than atorvastatin, including after outlier removal and in low risk-of-bias analyses. Benefits were more evident in diabetes/dyslipidemia and in patients with higher baseline CRP or hypertension, while effects on IL-6, adiponectin, and TNF-α were inconclusive. These findings support tailoring statin selection to the patient’s clinical profile.Change in CRP From Baseline to Follow-UpFor image description, please refer to the figure legend and surrounding text.CRP Reduction by Disease SubgroupFor image description, please refer to the figure legend and surrounding text.