A review of the effects of statins in systemic sclerosis

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• 作者：Karim Ladak ; MD^a ; Janet E. Pope ; MD ; MPH ; FRCPC^b ; ^c ; ^{janet.pope@sjhc.london.on.ca" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Systemic sclerosis (scleroderma) ; Statins ; Hydroxy-methyl-glutaryl-CoA inhibitors ; Review ; Fibroblasts ; Cytokines ; Endothelial progenitor cells ; Pleiotropic ; Animal models ; Digital ulcers ; Trials
• 刊名：Seminars in Arthritis and Rheumatism
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：45
• 期：6
• 页码：698-705
• 全文大小：419 K

文摘

We performed a literature review assessing possible benefits of statins in systemic sclerosis (SSc).

Methods

PubMed, Embase, Cochrane Databases, and Medline were searched. Full-text English publications were identified in which the effects of statins in SSc were examined. Letters, review articles, and studies on morphea were excluded.

Results

In all, 18 of 404 studies were relevant. In vitro, statins decreased transcription and translation of IL-6 and collagen, with reversal via mevalonate. Animal studies demonstrated reduced production of Ras (a protein superfamily of GTPases), Rho (part of the Ras superfamily), and extracellular signal-regulated kinases (ERK), less fibrosis and myofibroblast transdifferentiation, and improved macrovasculature. In human studies, IL-6, an inflammatory cytokine, was reduced. Usually endothelial progenitor cell concentrations increased, and flow-mediated dilatation improved. Raynaud’s phenomenon, digital ulcers, and physician global assessments improved in the majority of studies of statin treatment in SSc. None of the 256 patients receiving statins experienced transaminitis or myopathy.

Conclusions

Not all findings were consistent. However, in general, in vitro, animal, and human studies demonstrated benefit in SSc pathophysiology, likely mediated through inhibition of lipid intermediate synthesis. Clinical improvement in SSc circulatory complications was observed. Statins seemed safe and well tolerated in SSc. Larger longer-term multi-site randomized trials are needed to further determine the role of statins as adjunctive treatment of this complex, heterogeneous connective tissue disease.