Mostafa A Khalifa, Hamzah M Alghzawi, Shehabeldin S Anan, Ahmad Al Rifai, Ayah A Anwar, Hayder Ali Raheem Al-Saedi, Eman Awady, Islam Masood, Mohamed Elsayed Badr, Mohamed Ismail, Obada Muayaid, Omar M Ahmed, Osama Bdarnh, Sarah Alkhatib, Fares Elnagar, Yasser Hegazi, Mohammad Jebril
Statins improve inflammatory and endothelial pathways in systemic sclerosis, but these findings should be interpreted cautiously, as clinical benefits remain minimal. Randomized trials are required to further study statins' therapeutic role beyond biochemical modulation.
INTRODUCTION: Systemic sclerosis (SSc) is driven by persistent inflammation and microvascular damage. Statins are hypothesized to offer vasculoprotective effects beyond lipid-lowering. We systematically evaluated the efficacy and safety of statins in SSc across biochemical, vascular, and patient-centred outcomes.
METHODS: Following PRISMA guidelines, a systematic search of four electronic databases was conducted up to August 2025. Ten studies involving 323 patients were included. Pooled estimates were calculated using a random-effects model. Heterogeneity and sensitivity analyses were performed, and study quality was assessed using standardized appraisal tools.
RESULTS: Statin therapy was associated with significant biochemical improvements. Compared with baseline or placebo, CRP decreased by an average of 0.70 mg/L, IL-6 by 5.56 pg/mL, and fibrinogen by 40 mg/dL. Endothelial markers showed similar reductions: 0.85 pg/mL for ET-1, 23.17 IU/dL for vWF, and 25 ng/mL for ICAM-1. Total cholesterol and LDL decreased by mean differences of 0.93 mmol/L and 0.76 mmol/L, respectively, while HDL showed no meaningful change.
CONCLUSION: Statins improve inflammatory and endothelial pathways in systemic sclerosis, but these findings should be interpreted cautiously, as clinical benefits remain minimal. Randomized trials are required to further study statins' therapeutic role beyond biochemical modulation.