Comparative effects of atorvastatin and rosuvastatin on inflammatory biomarkers: a systematic review and meta-analysis of randomized head-to-head trials

Background Inflammation contributes significantly to cardiovascular disease progression. While both atorvastatin and rosuvastatin have anti-inflammatory effects, evidence directly comparing their effects on inflammatory biomarkers is limited and inconsistent. This study aimed to compare their effects through a meta-analysis of randomized controlled trials (RCTs). Methods We performed a systematic review and meta-analysis of head-to-head RCTs comparing atorvastatin and rosuvastatin on inflammatory biomarkers. On August 14, 2024, we searched PubMed, Web of Science, Scopus, and CENTRAL, and subsequently searched ClinicalTrials.gov for unpublished studies. We included RCTs directly comparing the two statins and reported changes in C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), or adiponectin. Using a random-effects model, we pooled the data and reported the results as mean differences (MD) or standardized mean differences (SMD) with 95% confidence intervals (CIs). We assessed risk of bias using the Cochrane RoB 2 tool. The review protocol was registered in PROSPERO (CRD42024579712) (see the PRISMA 2020 for Abstracts checklist). Results A total of 35 RCTs ( n = 6,148) were included. The pooled effect showed no significant difference in CRP reduction (MD: − 0.53 mg/L; 95% CI: − 1.10 to 0.05; p = 0.07; I 2 = 82%). After excluding one outlier, rosuvastatin showed a greater reduction (MD: − 0.16 mg/L; 95% CI: − 0.28 to − 0.03; p = 0.01; I 2 = 63%). The SMD also favored rosuvastatin (SMD: − 0.17; 95% CI: − 0.31 to − 0.04; p = 0.01). Sensitivity analysis among low risk-of-bias studies ( n = 9) showed a smaller yet significant reduction (MD: − 0.08 mg/L; 95% CI: − 0.16 to − 0.01; p = 0.03). We observed no significant differences for IL-6 ( n = 484; MD: − 0.82; 95% CI: − 3.02 to 1.38), adiponectin ( n = 257; MD: − 1.78; 95% CI: − 4.70 to 1.14), or TNF-alpha ( n = 309; MD: 0.23; 95% CI: − 0.05 to 0.52). Meta-regression identified baseline CRP, HDL, and hypertension prevalence as predictors of CRP reduction. Conclusions Rosuvastatin showed a modest but statistically significant advantage over atorvastatin in lowering CRP, especially in patients with higher baseline inflammation or hypertension. Evidence for other biomarkers remains inconclusive. Tailoring statin therapy to patient profiles may optimize benefits.